Monica Neagu
Mihaela Adriana Ilie
Ancuta Mihai
Constantin Caruntu- 1Immunology Department, “Victor Babes” National Institute, Bucharest, Romania
- 2Pathology Department, Colentina Clinical Hospital, Bucharest, Romania
- 3Faculty of Biology, University of Bucharest, Bucharest, Romania
- 4Dermatology Department, Kalmar County Hospital, Kalmar, Sweden
- 5Internal Medicine - Rheumatology Department, Carol Davila Central Military Emergency University Hospital, Bucharest, Romania
- 6Faculty of Medicine, Titu Maiorescu University, Bucharest, Romania
- 7Réseau de l’arc, Hôpital de Moutier, Berne, Switzerland
- 8Department of Physiology, The “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
- 9Department of Dermatology, “Prof. N.C. Paulescu, National Institute of Diabetes, Nutrition and Metabolic Diseases, Bucharest, Romania
Editorial on the Research Topic
Autoimmunity: novel insights and future perspectives
This Research Topic on autoimmunity was a success, attracting the attention of many research teams worldwide and resulting in no fewer than 40 articles, of which 60% were original studies. The work presented focuses on rheumatoid arthritis, psoriatic arthritis, psoriasis, lupus, and several other autoimmune diseases and autoimmune-related conditions. As recent large cohort studies have shown that one in 10 individuals is diagnosed with an autoimmune disease, and their incidence is rising, especially in Western countries (1, 2), this Research Topic gathers the most recent original studies and review articles on this important human condition.
Autoimmune diseases represent a complex and heterogeneous group of disorders characterized by immune dysregulation, chronic inflammation, and multiorgan involvement (2–8). Over the past decades, advances in immunology, genetics, and systems biology have deepened our understanding of the mechanisms underlying these diseases (4–17), while simultaneously uncovering novel biomarkers and therapeutic targets (4, 18–28).
This Research Topic brings together cutting-edge studies that collectively provide new insights into the pathogenesis, systemic consequences, and emerging treatment strategies for autoimmune diseases, with a focus on rheumatoid arthritis (RA), psoriatic arthritis (PsA), ankylosing spondylitis (AS), psoriasis (PsO), and antiphospholipid syndrome (APS). By integrating insights from immunology, microbiology, proteomics, genetics, and innovative modeling platforms, these articles offer multidimensional perspectives on autoimmunity.
The majority of the contributions focus on rheumatoid arthritis and psoriatic arthritis. A central theme in this Research Topic is immune dysregulation as a driver of disease (9, 29–31). Yan et al. explored the immunological landscape of difficult-to-treat RA (D2T RA), revealing a marked reduction in regulatory T cells (Tregs) accompanied by an increased Th17/Treg ratio, reflecting a disrupted immune balance that correlates with heightened disease activity. Importantly, low-dose interleukin-2 therapy successfully restored Treg populations without significant adverse effects, highlighting the potential of targeted immunomodulation to re-establish immune homeostasis in refractory RA. This study emphasizes the pivotal role of Tregs as a hallmark of severe disease and underscores the therapeutic promise of restoring immune equilibrium rather than broadly suppressing inflammation.
Complement activation is another dimension of immune dysregulation that is particularly relevant in systemic autoimmune pathologies (32–35). Erkan et al. investigated complement activation in patients positive for antiphospholipid antibodies (aPLs) who did not have other systemic autoimmune rheumatic diseases. They demonstrated that cell-bound complement activation products (CB-CAPs) on B lymphocytes, erythrocytes, and platelets are more sensitive indicators of complement activity than traditional C3/C4 measurements. Elevated CB-CAPs were most pronounced in patients with microvascular APS, thrombocytopenia, or hemolytic anemia, and they remained stable over 6 to 12 months. These findings suggest that CB-CAPs could serve as reliable biomarkers for monitoring disease activity and thrombosis risk, providing a tool for more precise clinical management of APS, where conventional complement measures may underestimate activation. Feng et al. highlighted the crucial role of endothelial cells (ECs) in the pathogenesis of APS, an autoimmune disease associated with recurrent thromboses and recurrent pregnancy losses (36–42). Antiphospholipid antibodies (aPLs) were found to act as both biomarkers and pathogenic factors, directly interacting with EC receptors and activating intracellular pathways involved in various pathophysiological mechanisms (37, 43–47). In vitro and in vivo studies have described multiple molecular mechanisms through which ECs mediate the effects of aPLs on vascular function (48–50). These findings provide an integrated understanding of the role of ECs in APS and identify new potential targets for diagnosis and the development of personalized therapies.
Wang et al. explored the role of the ubiquitin-proteasome system (UPS) in the pathogenesis of APS, an autoimmune disease characterized by thromboses and pregnancy complications associated with persistent elevation of aPLs (51). UPS imbalance promotes the activation of proinflammatory and prothrombotic pathways, contributing to disease progression (52, 53). The summarized in vivo studies presented in their work suggest that low-dose proteasome inhibitors may alleviate the clinical manifestations of APS by reducing inflammatory mediators (54, 55). These results indicate that targeting the UPS could represent a novel therapeutic strategy for controlling the inflammatory and thrombotic processes associated with this condition.
Expanding the scope of autoimmune interactions, Duan et al. employed bidirectional Mendelian randomization to elucidate causal relationships between psoriasis, psoriatic arthritis, and multiple autoimmune diseases, including systemic lupus erythematosus (SLE), Crohn’s disease (CD), Hashimoto’s thyroiditis (HT), RA, vitiligo, and AS. Their analysis revealed that CD and vitiligo increase the risk of developing psoriasis (PsO), whereas bullous pemphigoid appears to reduce it. For PsA, risk factors extended to CD, HT, RA, AS, SLE, and vitiligo. These results underscore the interconnectivity of autoimmune disorders and highlight the importance of carefully monitoring for disease progression, particularly in patients presenting with coexisting autoimmune conditions. This study exemplifies how genetic epidemiology can contribute to risk stratification and early intervention strategies, guiding personalized patient management. Proteome-wide analyses complement genetic studies by identifying causal proteins that may serve as biomarkers or therapeutic targets.
Zhao et al. performed a Mendelian randomization study examining 1,837 plasma proteins in relation to PsA risk. They identified seven proteins associated with disease susceptibility, notably interleukin-10 (IL-10), which is inversely linked with PsA, and apolipoprotein F (APOF), which is positively associated with the disease. Colocalization analyses confirmed genetic overlap with disease risk, while phenome-wide assessments suggested broader systemic effects. These findings provide novel insights into PsA etiology and highlight IL-10 and APOF as potential targets for therapeutic intervention, bridging the gap between molecular discovery and clinical translation.
Similarly, in AS, a chronic immune-mediated arthritis with an incompletely understood pathogenesis that primarily affects the axial joints (56–58), Zhao et al. identified eight plasma proteins causally associated with disease risk, including AIF1, TNF, FKBPL, AGER, ALDH5A1, and ACOT13. Colocalization analyses confirmed these as shared causal variants, while phenome-wide assessments highlighted potential adverse effects, offering guidance for drug development. Together, these studies illustrate the power of multi-omics approaches in elucidating the molecular mechanisms underlying autoimmune diseases and supporting the design of targeted therapies.
The role of the microbiome is emerging as a critical modifier of autoimmune pathogenesis (59–66). Lu et al. reviewed the contributions of the gut and oral microbiota to RA, emphasizing that dysbiosis in the gut—including the expansion of Prevotella species—and colonization by oral pathogens, such as Porphyromonas gingivalis and Aggregatibacter actinomycetem comitans, can promote the production of anti-citrullinated protein antibodies (ACPAs), a hallmark of RA.
Bacterial extracellular vesicles were also highlighted as potent mediators of systemic inflammation, suggesting that microbial communities at mucosal sites can modulate systemic autoimmunity.
Complementing this, Yang et al. demonstrated in a collagen-induced arthritis rat model that oral administration of Bifidobacterium animalis BD400 alleviates disease progression by modulating gut microbiota composition, enhancing intestinal barrier proteins, and downregulating histidine metabolites implicated in inflammation. This dual approach—mechanistic understanding of microbial contributions and experimental manipulation—provides compelling evidence for microbiota-targeted interventions as potential preventive or adjunctive strategies in autoimmune disorders. Bridging molecular and clinical perspectives, Liu et al. explored the systemic consequences of RA and revealed a causal association with increased epilepsy risk through Mendelian randomization. This finding underscores the fact that autoimmune inflammation extends beyond the affected joints, necessitating comprehensive patient management that considers neurological comorbidities. Similarly, Guo et al. evaluated therapeutic interventions in severe systemic rheumatic diseases by comparing plasma exchange alone with a combination of IVIG and methylprednisolone pulse therapy. Their retrospective analysis demonstrates that adding IVIG/IVMP does not improve survival or ICU stay but increases infection rates, suggesting that simplified monotherapy may suffice in critical care contexts, reducing complications while maintaining efficacy.
Innovative technological platforms further expand the toolkit for understanding autoimmune pathogenesis. Zhang et al. introduced a synovial joint-on-a-chip model that accurately mimics the joint microenvironment by integrating fluid dynamics, mechanical stimulation, and intercellular communication. This platform facilitates preclinical modeling of RA, enabling precise evaluation of inflammation, drug efficacy, and personalized therapeutic strategies. Coupled with mechanistic and molecular insights from the other studies, such platforms can accelerate translational research, bridging the gap between bench and bedside.
Collectively, these contributions highlight a unifying theme: autoimmunity is a multidimensional process shaped by immune dysregulation, genetic predisposition, proteomic signatures, microbial interactions, and systemic consequences. Across RA, PsA, PsO, AS, and APS, these studies underscore the importance of integrating molecular, microbiological, and clinical data to contribute to risk stratification, biomarker discovery, and targeted interventions.
The convergence of genetic epidemiology, proteomics, microbiome research, and advanced modeling technologies emphasizes that autoimmune diseases are not single-organ pathologies but rather a networked, systemic phenomenon. Furthermore, the research presented in this Research Topic emphasizes translational and clinical implications. Targeted immunotherapies, such as low-dose IL-2 in D2T RA, demonstrate the potential to restore immune balance with precision. Proteomic analyses identify actionable biomarkers and druggable targets in PsA and AS, paving the way for personalized therapeutics. Microbiota interventions show promise for disease prevention or modulation of progression, while organ-on-a-chip platforms provide realistic preclinical models to optimize drug development and predict adverse effects. Together, these advances signify a paradigm shift toward integrated, precision medicine approaches in autoimmune disease management.
Lupus is another chronic autoimmune disease discussed in this Research Topic. It is characterized by dysregulated immune responses that lead to inflammation and immune-mediated injury, which may affect various organs (67–69). There are four original papers dedicated to lupus in this Research Topic. The serological profile of SLE was explored by Nicola et al. and anti-dsDNA antibodies were found to be statistically significant for both malar rash and proteinuria; anti-Ro/SSA antibodies were also found to have an association with photosensitivity and pericarditis; additionally, an association was found between anti-Ro antibodies and proteinuria, but only when anti-dsDNA antibodies were present. A similar study focusing on another circulatory marker, the Myc-induced nuclear antigen (Mina) 53 protein, was evaluated in SLE patients by Zamani et al. The study showed that SLE patients have significant increases in Mina53 serum levels along with Mina53 gene expression. Moreover, Mina53 serum levels and gene expression correlated with SLE disease and its severity. Szabó et al. studied circulating immune cell subsets in SLE. Peripheral T-cells, NK-cells, NKT-cells, B-cells, and monocytes were investigated for their glycosylation patterns, and the authors reported that these alterations correlate with disease severity in SLE, which may have implications for the pathogenesis of this condition. Circulatory neutrophils are important players in SLE (70–72) and were investigated by Wang et al. Their report shows that immune complex-driven RNA-sensing by TLR8 in neutrophils is a major mechanism of neutrophil activation in this systemic autoimmune disease. Moreover, the study emphasizes that patients with elevated neutrophil activation and the presence of RNA-containing immune complexes can undergo therapies that rely on TLR8 inhibition and RNA removal. In their complex study, Kramer et al. have evaluated IgE autoantibodies to nuclear antigens in patients with different connective tissue diseases (CTDs), such as SLE, Sjögren’s syndrome (SS), and mixed connective tissue disease (MCTD). Serum analysis of 342 subjects revealed that IgE anti-SSA/Ro-, -SSB/La-, -RNP-, and -dsDNA antibodies exhibit high frequency and specificity for the evaluated CTDs. Moreover, the authors showed that the investigated antibodies may correlate with disease activity and cutaneous or pulmonary involvement. These results demonstrate the potential value of IgE autoantibodies as biomarkers of disease activity and severity, suggesting new directions for the differential diagnosis and therapeutic monitoring of systemic autoimmune diseases.
The review by Xu et al. examined the implications of sterol regulatory element-binding proteins (SREBPs) transcription factors in the pathogenesis of autoimmune rheumatic diseases, such as SLE, RA, and gout. SREBPs regulate lipid metabolism and cholesterol synthesis, thereby influencing cytokine production, inflammation, and the proliferation of germinal center B (GCB) cells. Dysregulation of these pathways contributes to pathological immune activation and the tissue damage characteristic of these diseases (73–77). Identifying the role of SREBPs in the interaction between metabolism and the immune response opens innovative therapeutic perspectives that aim to control inflammation through the regulation of cellular metabolic processes.
Psoriasis, one of the most common inflammatory skin diseases involving both autoimmune and autoinflammatory mechanisms (78–84), was also presented in our Research Topic with two original papers. Raam et al. described the results of the CRYSTAL study (EUPAS36459), a cross-sectional, retrospective study of Pso adult patients from several Central and Eastern European countries. The patients were evaluated while undergoing treatment with either biological or conventional agents. The Psoriasis Area and Severity Index (PASI), Dermatology Life Quality Index (DLQI), and Psoriasis Work Productivity and Activity Impairment (WPAI-PSO) were evaluated upon therapies. The study showed better disease control in the biological treatment group compared to the non-biological treatment group. Another contribution to our Research Topic regarding psoriasis was the original study by Shi et al., who investigated the role of odd-chain fatty acids (OCFAs)in Pso. The authors found that high plasma levels of total OCFAs were positively associated with white blood cell (WBC) and neutrophil counts. This study highlights that plasma OCFAs may have an immunomodulatory role in immune regulation, disease progression, and comorbidity management in psoriasis.
Other original studies cover various topics in autoimmunity. In a two-sample bidirectional Mendelian randomization study by Yuan et al., reciprocal causality was shown between plasma metabolites and autoimmune diseases. For example, four metabolites were associated with inflammatory bowel disease (IBD), and the highest number of associated metabolites was 37 in type 1 diabetes. The study provides data on discovering new therapeutic targets from the metabolite domain in autoimmunity. The study by Chang et al. investigated the genetic link between inflammatory bowel disease with IBD and conjunctivitis—two frequently associated conditions (85, 86) whose connection remains insufficiently understood from a genetic perspective. Genome-wide association studies (GWAS) and Mendelian randomization methods revealed a significant genomic correlation between IBD and conjunctivitis, limited to chromosome 11. These results support the existence of a shared causal mechanism, reinforcing the genetic basis of immunoinflammatory comorbidities. These findings contribute to a broader understanding of the common etiology of autoimmune diseases and may support the development of integrated diagnostic and therapeutic strategies.
Klekotka et al. conducted a systematic literature review to examine clinical evidence on therapies that aim to restore immune homeostasis in autoimmune diseases such as asthma, atopic dermatitis, RA, SLE, and ulcerative colitis. Their analysis of 26 publications revealed a lack of consensus regarding markers and criteria for assessing immune resolution; however, it identified associations between T-cell regulatory biomarkers and clinical remission. The study highlights the potential of the “immune resolution” concept as a marker of durable remissions, along with the urgent need for methodological standardization in clinical studies.
Pemphigus vulgaris, an autoimmune disease affecting the skin and mucous membranes (87–91), was studied by Zakrzewicz et al. Their original study focused on IgG autoantibodies directed against desmosomal adhesion proteins (e.g., desmoglein-3 and -1), which cause loss of keratinocyte adhesion. Their results show that FcRn (neonatal Fc receptor) binding is necessary for the pathogenicity of recombinant anti-desmoglein-3 antibodies in keratinocytes. The data suggest that the role of FcRn in autoimmune diseases is versatile and cell-type dependent. The report of Hou and Chen described a rare case of pemphigus vegetans, a distinct form of pemphigus characterized by vegetative lesions in intertriginous areas. In this condition, the most common autoantibodies target desmoglein 3 (92, 93). This case underscores the importance of prompt diagnosis and appropriate immunosuppressive therapy, demonstrating the effectiveness of modern therapeutic approaches in treating severe forms of pemphigus.
Severe burn injury can generate autoantigens, and Turan et al. focused their study on the liver-derived selenium (Se) transporter selenoprotein P (SELENOP) as a marker of severe inflammation in the acute post-burn phase. The study presented the presence of SELENOP-aAb correlated with severe burn injury, which could be relevant for severely affected patients.
Our Research Topic also hosts several insightful reviews on this topic. Gong et al. reviewed the hypoxic microenvironment and the role of hypoxia-inducible factor-1 (HIF-1)in RA, SLE, multiple sclerosis (MS), and dermatomyositis (DM). Therapeutic strategies that aim at targeting hypoxic pathways may highlight new avenues for intervention. Immune tolerance is a popular topic in autoimmunity (94–98) and Wixler et al. reviewed the role of small spleen polypeptides (SSPs), which regulate peripheral immune tolerance. For example, SSPs reduced the progression of experimental psoriasis or arthritis in animal models (99). Complex mechanisms triggered by SSPs induce a tolerogenic state in dendritic cells, generating Foxp3+ immunosuppressive regulatory Treg cells. T cells are also the subject of the review by Dwyer et al., but in the context of autoimmune diabetes. Key antigenic T lymphocyte epitopes were identified as contributors to this autoimmune pathology, and the role of islet-specific T lymphocyte populations was also discussed.
An interesting opinion article by Mustelin and Andrade offered a different perspective on the ‘loss of tolerance’ concept in autoimmunity. The authors discussed four dilemmas regarding loss of tolerance, and their neoantigen hypothesis brought a critical rethinking and re-examination of the current loss of tolerance concept.
The involvement of gut microbiota is a recent and important topic of discussion in autoimmunity (61, 100–109) and Wang et al. reviewed its influence in this domain. The authors showed the complex interplay between the gut microbiota, the host, and the immune system, particularly in diseases such as SLE, RA, Sjögren’s syndrome, T1DM, ulcerative colitis, and Pso (110–125).
The topic of the gut microbiota was also discussed in the contribution by Freuchet et al., which addressed the importance of inflammation and biological variability in synucleinopathies, such as Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. This review highlights the central role of neuroinflammation, which is mediated by central nervous system-resident cells, peripheral immune cells, and gut dysbiosis, in triggering and progressing neurodegeneration (126–129). Sex-based differences in prevalence and immune response are also emphasized, with major therapeutic implications. The article supports the need for personalized approaches and specific biomarkers for the diagnosis and tailored treatment of synucleinopathies.
Shi et al. reviewed the role of one type of mesenchymal cell, fibroblasts, in autoimmune diseases and their involvement in dermatological autoimmune conditions such as Pso, vitiligo, and atopic dermatitis. Fibroblast heterogeneity was highlighted in each of these autoimmune diseases, implying new future research directions and possibly new therapeutic targets. Also in the dermatological field, Ungureanu et al. reviewed the autoimmune mechanisms of melanoma (130–132), the most severe form of skin cancer (133), with a very complex pathogenesis (134–140). They emphasized that patients with vitiligo are less likely to develop melanoma (141, 142). Moreover, their article highlighted that drug-associated leukoderma (DAL) is a marker of prolonged disease-free survival in melanoma patients treated with immune checkpoint inhibitors (143, 144).
A more exotic form of autoimmunity, acute non-biliary pancreatitis (ANBP), was investigated in an original study by Anılır et al. Toll-Like Receptor 4 (TLR4) and Toll-Like Receptor 2 (TLR2) gene polymorphisms were studied, and their research findings point to TLR-4 Rs4986790 polymorphism groups that can have diagnostic value in ANBP.
The study by Barzilai et al. investigated the role of vasculitis as a potential marker of disease severity in familial Mediterranean fever (FMF), a genetic autoinflammatory condition (145, 146). A comparative analysis of 27 FMF patients with vasculitis and 100 without vasculitis revealed an association with earlier disease onset, increased severity, higher colchicine doses, and a higher frequency of homozygosity for the M694V mutation. Although vasculitis was not identified as an independent factor of severity, its presence may indicate a more aggressive disease course. The results highlight the clinical value of vasculitis as a monitoring and risk-stratification indicator in the management of FMF patients.
The study by Li et al. explored the role of ferroptosis, a form of cell death dependent on oxidative stress (147, 148), in the pathogenesis of thyroid-associated orbitopathy (TAO), a complex autoimmune inflammatory disease (149, 150). Through bioinformatic analysis of gene datasets and experimental validation, the genes ACO1 and HCAR1 were identified as significant molecular markers, showing reduced expression in the orbital adipose tissue of patients. Correlations with immune cell infiltration suggested a pathogenic mechanism in which macrophages play a key role. These findings provide new insights into the pathophysiological processes underlying TAO and propose ACO1 and HCAR1 as optimal feature genes (OFGs) of ferroptosis, suggesting their potential as diagnostic and therapeutic molecular targets in TAO.
Wang et al. proposed a nomogram-based model to estimate the risk of arteriolar lesions in patients with IgA nephropathy, which is a major cause of chronic kidney disease (151–153). Based on a retrospective analysis of 547 cases, predictive factors such as age, mean arterial pressure, eGFR, and serum uric acid were identified. The model demonstrated good performance (C-index 0.72–0.78) and accuracy in predicting arteriolar damage. This tool provides a simple and reliable method for assessing renal prognosis, enabling early intervention in the management of patients with IgA nephropathy. Also in the nephropathy domain, the review by Zhang et al. synthesized evidence regarding the involvement of the complement system in anti-glomerular basement membrane glomerulonephritis (anti-GBM GN), a rare autoimmune disease that often progresses to end-stage renal disease (154). Prior studies have demonstrated the activation of all three complement pathways and a correlation between complement-related proteins and lesion severity. The identification of biomarkers of complement activation enables risk stratification of renal deterioration and paves the way for the use of complement inhibition as a novel therapeutic strategy (155–159). These findings underscore the importance of complement function assessment in the prognosis and management of patients with anti-GBM GN.
In the therapy domain, the study by Zhang and Sun evaluated the potential of genetically engineered T-cell therapies (CAR-T and CAR-Treg) for treating autoimmune kidney diseases that are refractory to conventional therapies. By reprogramming T cells to target autoreactive B cells or antibody-secreting plasma cells, these therapies can modulate inflammation and prevent tissue damage (160, 161). The review summarizes recent fundamental and clinical research, highlighting the efficacy of precise targeting in immune regulation. These advances open revolutionary therapeutic perspectives in immune-mediated kidney diseases, marking a transition toward personalized cellular medicine.
In conclusion, this Research Topic captures the dynamic landscape of autoimmune research, emphasizing mechanistic understanding, biomarker discovery, and innovative therapeutic strategies. By linking immunology, genetics, proteomics, microbiology, and technology, these studies collectively advance our understanding of autoimmune pathogenesis and offer new avenues for personalized interventions. As the field moves forward, these interdisciplinary approaches will be essential for translating mechanistic discoveries into clinical impact, ultimately improving patient outcomes and fostering the development of novel, targeted therapies for autoimmune diseases.
Author contributions
CC: Writing – original draft, Writing – review & editing. MN: Writing – original draft, Writing – review & editing. MI: Writing – original draft, Writing – review & editing. AM: Writing – original draft, Writing – review & editing.
Conflict of interest
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The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.
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References
1. Conrad N, Misra S, Verbakel JY, Verbeke G, Molenberghs G, Taylor PN, et al. Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: A population-based cohort study of 22 million individuals in the UK. Lancet. (2023) 401:1878–90. doi: 10.1016/S0140-6736(23)00457-9
2. Cao F, Liu YC, Ni QY, Chen Y, Wan CH, Liu SY, et al. Temporal trends in the prevalence of autoimmune diseases from 1990 to 2019. Autoimmun Rev. (2023) 22:103359. doi: 10.1016/j.autrev.2023.103359
3. Cao F, He Y-S, Wang Y, Zha C-K, Lu J-M, Tao L-M, et al. Global burden and cross-country inequalities in autoimmune diseases from 1990 to 2019. Autoimmun Rev. (2023) 22:103326. doi: 10.1016/j.autrev.2023.103326
4. Xiang Y, Zhang M, Jiang D, Su Q, and Shi J. The role of inflammation in autoimmune disease: A therapeutic target. Front Immunol. (2023) 14:1267091. doi: 10.3389/fimmu.2023.1267091
5. Pisetsky DS. Pathogenesis of autoimmune disease. Nat Rev Nephrol. (2023) 19:509–24. doi: 10.1038/s41581-023-00720-1
6. Miller FW. The increasing prevalence of autoimmunity and autoimmune diseases: an urgent call to action for improved understanding, diagnosis, treatment, and prevention. Curr Opin Immunol. (2023) 80:102266. doi: 10.1016/j.coi.2022.102266
7. Lincoln MR, Connally N, Axisa PP, Gasperi C, Mitrovic M, van Heel D, et al. Genetic mapping across autoimmune diseases reveals shared associations and mechanisms. Nat Genet. (2024) 56:838–45. doi: 10.1038/s41588-024-01732-8
8. Wen X and Li BA. Population-based study on autoimmune disease. Lancet. (2023) 401:1829–31. doi: 10.1016/S0140-6736(23)00621-9
9. Weyand CM and Goronzy JJ. The immunology of rheumatoid arthritis. Nat Immunol. (2021) 22:10–8. doi: 10.1038/s41590-020-00816-x
10. Tsokos GC. The immunology of systemic lupus erythematosus. Nat Immunol. (2024) 25:1332–43. doi: 10.1038/s41590-024-01898-7
11. Harroud A and Hafler DA. Common genetic factors among autoimmune diseases. Sci (80-.). (2023) 380:485–90. doi: 10.1126/science.adg2992
12. Bianchi M, Kozyrev SV, Notarnicola A, Sandling JK, Pettersson M, Leonard D, et al. Unraveling the genetics of shared clinical and serological manifestations in patients with systemic inflammatory autoimmune diseases. Arthritis Rheumatol. (2025) 77:212–25. doi: 10.1002/art.42988
13. Padyukov L. Genetics of rheumatoid arthritis. Semin Immunopathol. (2022) 44:47–62. doi: 10.1007/s00281-022-00912-0
14. Tampa M, Neagu M, Caruntu C, Constantin C, and Georgescu S. Skin inflammation—A cornerstone in dermatological conditions. J Pers Med. (2022) 12:1370. doi: 10.3390/jpm12091370
15. Surcel M, Munteanu A, Huică R, Isvoranu G, Pârvu I, Constantin C, et al. Reinforcing involvement of NK cells in psoriasiform dermatitis animal model. Exp Ther Med. (2019) 18(6):4956-4966. doi: 10.3892/etm.2019.7967
16. Surcel M, Huică R-I, Munteanu A, Isvoranu G, Pârvu I, Ciotaru D, et al. Phenotypic changes of lymphocyte populations in psoriasiform dermatitis animal model. Exp Ther Med. (2018) 17(2):1030-1038. doi: 10.3892/etm.2018.6978
17. Caruntu C, Boda D, Dumitrascu G, Constantin C, and Neagu M. Proteomics focusing on immune markers in psoriatic arthritis. biomark Med. (2015) 9:513–28. doi: 10.2217/bmm.14.76
18. Frazzei G, van Vollenhoven RF, de Jong BA, Siegelaar SE, and van Schaardenburg D. Preclinical autoimmune disease: A comparison of rheumatoid arthritis, systemic lupus erythematosus, multiple sclerosis and type 1 diabetes. Front Immunol. (2022) 13:899372. doi: 10.3389/fimmu.2022.899372
19. Laigle L, Chadli L, and Moingeon P. Biomarker-driven development of new therapies for autoimmune diseases: current status and future promises. Expert Rev Clin Immunol. (2023) 19:305–14. doi: 10.1080/1744666X.2023.2172404
20. Sciascia S, Bizzaro N, Meroni PL, Dimitrios B, Borghi MO, Bossuyt X, et al. Autoantibodies testing in autoimmunity: diagnostic, prognostic and classification value. Autoimmun Rev. (2023) 22:103356. doi: 10.1016/j.autrev.2023.103356
21. Fenton KA and Pedersen HL. Advanced methods and novel biomarkers in autoimmune diseases − a review of the recent years progress in systemic lupus erythematosus. Front Med. (2023) 10:1183535. doi: 10.3389/fmed.2023.1183535
22. Mihai A, Caruntu C, Jurcut C, Blajut FC, Casian M, Opris-Belinski D, et al. The spectrum of extraglandular manifestations in primary Sjögren’s syndrome. J Pers Med. (2023) 13:961. doi: 10.3390/jpm13060961
23. Mihai A, Chitimus DM, Jurcut C, Blajut FC, Opris-Belinski D, Caruntu C, et al. Comparative analysis of hematological and immunological parameters in patients with primary Sjögren’s syndrome and peripheral neuropathy. J Clin Med. (2023) 12:3672. doi: 10.3390/jcm12113672
24. Li S, Wu Y, Chen J, Shen S, Duan J, and Xu HE. Autoimmune diseases: targets, biology, and drug discovery. Acta Pharmacol Sin. (2024) 45:674–85. doi: 10.1038/s41401-023-01207-2
25. Song Y, Li J, and Wu Y. Evolving understanding of autoimmune mechanisms and new therapeutic strategies of autoimmune disorders. Signal Transduction Targeting Ther. (2024) 9:263. doi: 10.1038/s41392-024-01952-8
26. Huang J, Fu X, Chen X, Li Z, Huang Y, and Liang C. Promising therapeutic targets for treatment of rheumatoid arthritis. Front Immunol. (2021) 12:686155. doi: 10.3389/fimmu.2021.686155
27. Wu D, Xu-Monette ZY, Zhou J, Yang K, Wang X, Fan Y, et al. CAR T-cell therapy in autoimmune diseases: A promising frontier on the horizon. Front Immunol. (2025) 16:1613878. doi: 10.3389/fimmu.2025.1613878
28. Schett G, Mackensen A, and Mougiakakos D. CAR T-cell therapy in autoimmune diseases. Lancet. (2023) 402:2034–44. doi: 10.1016/S0140-6736(23)01126-1
29. James EA, Holers VM, Iyer R, Prideaux EB, Rao NL, Rims C, et al. Multifaceted immune dysregulation characterizes individuals at-risk for rheumatoid arthritis. Nat Commun. (2023) 14:7637. doi: 10.1038/s41467-023-43091-8
30. Baker KF, McDonald D, Hulme G, Hussain R, Coxhead J, Swan D, et al. Single-Cell Insights into Immune Dysregulation in Rheumatoid Arthritis Flare versus Drug-Free Remission. Nat Commun. (2024) 15:1063. doi: 10.1038/s41467-024-45213-2
31. Sahu S, Jain P, Deshmukh R, Samal PK, and Satapathy T. Ajazuddin. Psoriatic arthritis in transition: cytokine signaling, immune dysregulation, and therapeutic innovation. Inflammopharmacology. (2025) 33:4275–90. doi: 10.1007/s10787-025-01865-0
32. Jia C, Tan Y, and Zhao M. The complement system and autoimmune diseases. Chronic Dis Transl Med. (2022) 8:184–90. doi: 10.1002/cdt3.24
33. Java A and Kim AHJ. The role of complement in autoimmune disease-associated thrombotic microangiopathy and the potential for therapeutics. J Rheumatol. (2023) 50:730–40. doi: 10.3899/jrheum.220752
34. Coss SL, Zhou D, Chua GT, Aziz RA, Hoffman RP, Wu YL, et al. The complement system and human autoimmune diseases. J Autoimmun. (2023) 137:102979. doi: 10.1016/j.jaut.2022.102979
35. Galindo-Izquierdo M and Pablos Alvarez JL. Complement as a therapeutic target in systemic autoimmune diseases. Cells. (2021) 10:148. doi: 10.3390/cells10010148
36. Knight JS, Branch DW, and Ortel TL. Antiphospholipid syndrome: advances in diagnosis, pathogenesis, and management. BMJ. (2023) 380:e069717. doi: 10.1136/bmj-2021-069717
37. Raschi E, Borghi MO, Tedesco F, and Meroni PL. Antiphospholipid syndrome pathogenesis in 2023: an update of new mechanisms or just a reconsideration of the old ones? Rheumatology. (2024) 63:SI4–SI13. doi: 10.1093/rheumatology/kead603
38. Green D. Pathophysiology of antiphospholipid syndrome. Thromb Haemost. (2022) 122:1085–95. doi: 10.1055/a-1701-2809
39. Depietri L, Veropalumbo MR, Leone MC, and Ghirarduzzi A. Antiphospholipid syndrome: state of the art of clinical management. Cardiovasc Drugs Ther. (2025) 39:385–404. doi: 10.1007/s10557-023-07496-3
40. Knight JS and Erkan D. Rethinking antiphospholipid syndrome to guide future management and research. Nat Rev Rheumatol. (2024) 20:377–88. doi: 10.1038/s41584-024-01110-y
41. Xourgia E and Tektonidou MG. An update on antiphospholipid syndrome. Curr Rheumatol Rep. (2021) 23:84. doi: 10.1007/s11926-021-01051-5
42. Celia AI, Galli M, Mancuso S, Alessandri C, Frati G, Sciarretta S, et al. Antiphospholipid syndrome: insights into molecular mechanisms and clinical manifestations. J Clin Med. (2024) 13:4191. doi: 10.3390/jcm13144191
43. Bradacova P, Slavik L, Ulehlova J, Skoumalova A, Ullrychova J, Prochazkova J, et al. Current promising biomarkers and methods in the diagnostics of Antiphospholipid syndrome: A review. Biomedicines. (2021) 9:166. doi: 10.3390/biomedicines9020166
44. Sloan EE, Kmetova K, NaveenKumar SK, Kluge L, Chong E, Hoy CK, et al. Non-criteria antiphospholipid antibodies and calprotectin as potential biomarkers in pediatric antiphospholipid syndrome. Clin Immunol. (2024) 261:109926. doi: 10.1016/j.clim.2024.109926
45. Lambert M, Brodovitch A, Mège J-L, Bertin D, and Bardin N. Biological markers of high risk of thrombotic recurrence in patients with antiphospholipid syndrome: A literature review. Autoimmun Rev. (2024) 23:103585. doi: 10.1016/j.autrev.2024.103585
46. Devreese KMJ. Thrombosis in antiphospholipid syndrome: current perspectives and challenges in laboratory testing for antiphospholipid antibodies. Semin Thromb Hemost. (2025) 51:676–86. doi: 10.1055/s-0044-1791699
47. Yang L, Guo R, Liu H, Chen B, Li C, Liu R, et al. Mechanism of antiphospholipid antibody-mediated thrombosis in antiphospholipid syndrome. Front Immunol. (2025) 16:1527554. doi: 10.3389/fimmu.2025.1527554
48. Hollerbach A, Müller-Calleja N, Ritter S, Häuser F, Canisius A, Orning C, et al. Platelet activation by antiphospholipid antibodies depends on epitope specificity and is prevented by MTOR inhibitors. Thromb Haemost. (2019) 119:1147–53. doi: 10.1055/s-0039-1685453
49. Willis R, McDonnell TCR, Pericleous C, Gonzalez EB, Schleh A, Romay-Penabad Z, et al. PEGylated domain I of beta-2-glycoprotein I inhibits thrombosis in a chronic mouse model of the antiphospholipid syndrome. Front Immunol. (2022) 13:842923. doi: 10.3389/fimmu.2022.842923
50. Capozzi A, Manganelli V, Riitano G, Caissutti D, Longo A, Garofalo T, et al. Advances in the pathophysiology of thrombosis in antiphospholipid syndrome: molecular mechanisms and signaling through lipid rafts. J Clin Med. (2023) 12:891. doi: 10.3390/jcm12030891
51. Barilaro G, Coloma-Bazan E, Chacur A, Della Rocca C, Perez-Isidro A, Ruiz-Ortiz E, et al. Persistence of antiphospholipid antibodies over time and its association with recurrence of clinical manifestations: A longitudinal study from a single centre. Autoimmun Rev. (2022) 21:103208. doi: 10.1016/j.autrev.2022.103208
52. Luo X-B, Xi J-C, Liu Z, Long Y, Li L, Luo Z-P, et al. Proinflammatory effects of ubiquitin-specific protease 5 (USP5) in rheumatoid arthritis fibroblast-like synoviocytes. Mediators Inflamm. (2020) 2020:1–9. doi: 10.1155/2020/8295149
53. El-Kadiry AE-H and Merhi Y. The role of the proteasome in platelet function. Int J Mol Sci. (2021) 22:3999. doi: 10.3390/ijms22083999
54. Montiel-Manzano G, Romay-Penabad Z, Papalardo De Martínez E, Meillon-García LA, García-Latorre E, Reyes-Maldonado E, et al. In vivo effects of an inhibitor of nuclear factor-kappa B on thrombogenic properties of antiphospholipid antibodies. Ann N Y Acad Sci. (2007) 1108:540–53. doi: 10.1196/annals.1422.057
55. Pellom ST, Dudimah DF, Thounaojam MC, Sayers TJ, and Shanker A. Modulatory effects of bortezomib on host immune cell functions. Immunotherapy. (2015) 7:1011–22. doi: 10.2217/imt.15.66
56. Mauro D, Thomas R, Guggino G, Lories R, Brown MA, and Ciccia F. Ankylosing spondylitis: an autoimmune or autoinflammatory disease? Nat Rev Rheumatol. (2021) 17:387–404. doi: 10.1038/s41584-021-00625-y
57. Hwang MC, Ridley L, and Reveille JD. Ankylosing spondylitis risk factors: A systematic literature review. Clin Rheumatol. (2021) 40:3079–93. doi: 10.1007/s10067-021-05679-7
58. Wei Y, Zhang S, Shao F, and Sun Y. Ankylosing spondylitis: from pathogenesis to therapy. Int Immunopharmacol. (2025) 145:113709. doi: 10.1016/j.intimp.2024.113709
59. Shaheen WA, Quraishi MN, and Iqbal TH. Gut microbiome and autoimmune disorders. Clin Exp Immunol. (2022) 209:161–74. doi: 10.1093/cei/uxac057
60. Mangalam AK, Yadav M, and Yadav R. The emerging world of microbiome in autoimmune disorders: opportunities and challenges. Indian J Rheumatol. (2021) 16:57–72. doi: 10.4103/injr.injr_210_20
61. Miyauchi E, Shimokawa C, Steimle A, Desai MS, and Ohno H. The impact of the gut microbiome on extra-intestinal autoimmune diseases. Nat Rev Immunol. (2023) 23:9–23. doi: 10.1038/s41577-022-00727-y
62. Tsai Y-W, Dong J-L, Jian Y-J, Fu S-H, Chien M-W, Liu Y-W, et al. Gut microbiota-modulated metabolomic profiling shapes the etiology and pathogenesis of autoimmune diseases. Microorganisms. (2021) 9:1930. doi: 10.3390/microorganisms9091930
63. Jain P, Joshi N, Sahu V, Dominic A, and Aggarwal S. Autoimmune diseases and microbiome targeted therapies. Int Rev Cell Mol Biol. (2025) 395:133-156. doi: 10.1016/bs.ircmb.2024.12.007
64. Christovich A and Luo XM. Gut microbiota, leaky gut, and autoimmune diseases. Front Immunol. (2022) 13:946248. doi: 10.3389/fimmu.2022.946248
65. Chang S-H and Choi Y. Gut dysbiosis in autoimmune diseases: association with mortality. Front Cell Infect Microbiol. (2023) 13:1157918. doi: 10.3389/fcimb.2023.1157918
66. Mousa WK, Chehadeh F, and Husband S. Microbial dysbiosis in the gut drives systemic autoimmune diseases. Front Immunol. (2022) 13:906258. doi: 10.3389/fimmu.2022.906258
67. Siegel CH and Sammaritano LR. Systemic lupus erythematosus. JAMA. (2024) 331:1480. doi: 10.1001/jama.2024.2315
68. Arnaud L, Chasset F, and Martin T. Immunopathogenesis of systemic lupus erythematosus: an update. Autoimmun Rev. (2024) 23:103648. doi: 10.1016/j.autrev.2024.103648
69. Furment MM and Perl A. Immmunometabolism of systemic lupus erythematosus. Clin Immunol. (2024) 261:109939. doi: 10.1016/j.clim.2024.109939
70. Fresneda Alarcon M, McLaren Z, and Wright HL. Neutrophils in the pathogenesis of rheumatoid arthritis and systemic lupus erythematosus: same foe different M.O. Front Immunol. (2021) 12:649693. doi: 10.3389/fimmu.2021.649693
71. Kaplan MJ. Neutrophils in the pathogenesis and manifestations of SLE. Nat Rev Rheumatol. (2011) 7:691–9. doi: 10.1038/nrrheum.2011.132
72. O’Neil LJ, Kaplan MJ, and Carmona-Rivera C. The role of neutrophils and neutrophil extracellular traps in vascular damage in systemic lupus erythematosus. J Clin Med. (2019) 8:1325. doi: 10.3390/jcm8091325
73. Shimano H and Sato R. SREBP-regulated lipid metabolism: convergent physiology — Divergent pathophysiology. Nat Rev Endocrinol. (2017) 13:710–30. doi: 10.1038/nrendo.2017.91
74. Robinson G, Pineda-Torra I, Ciurtin C, and Jury EC. Lipid metabolism in autoimmune rheumatic disease: implications for modern and conventional therapies. J Clin Invest. (2022) 132(2):e148552. doi: 10.1172/JCI148552
75. Zhao Z, Zhao Y, Zhang Y, Shi W, Li X, Shyy JY-J, et al. Gout-induced endothelial impairment: the role of SREBP2 transactivation of YAP. FASEB J. (2021) 35(6):e21613. doi: 10.1096/fj.202100337R
76. Luo W, Adamska JZ, Li C, Verma R, Liu Q, Hagan T, et al. SREBP signaling is essential for effective B cell responses. Nat Immunol. (2023) 24:337–48. doi: 10.1038/s41590-022-01376-y
77. Kusnadi A, Park SH, Yuan R, Pannellini T, Giannopoulou E, Oliver D, et al. The cytokine TNF promotes transcription factor SREBP activity and binding to inflammatory genes to activate macrophages and limit tissue repair. Immunity. (2019) 51:241–57.e9. doi: 10.1016/j.immuni.2019.06.005
78. Sticherling M. Psoriasis and autoimmunity. Autoimmun Rev. (2016) 15:1167–70. doi: 10.1016/j.autrev.2016.09.004
79. McCormick T, Ayala-Fontanez N, and Soler D. Current knowledge on psoriasis and autoimmune diseases. Psoriasis Targets Ther. (2016) 7:7–32. doi: 10.2147/PTT.S64950
80. Liang Y, Sarkar MK, Tsoi LC, and Gudjonsson JE. Psoriasis: A mixed autoimmune and autoinflammatory disease. Curr Opin Immunol. (2017) 49:1–8. doi: 10.1016/j.coi.2017.07.007
81. Hawkes JE, Gonzalez JA, and Krueger JG. Autoimmunity in psoriasis: evidence for specific autoantigens. Curr Dermatol Rep. (2017) 6:104–12. doi: 10.1007/s13671-017-0177-6
82. Căruntu C, Boda D, Căruntu A, Rotaru M, Baderca F, and Zurac S. In vivo imaging techniques for psoriatic lesions. Rom J Morphol Embryol. (2014) 55:1191–6.
83. Batani A, Brănișteanu D, Ilie M, Boda D, Ianosi S, Ianosi G, et al. Assessment of dermal papillary and microvascular parameters in psoriasis vulgaris using in�vivo reflectance confocal microscopy. Exp Ther Med. (2017) 15(2):1241-1246. doi: 10.3892/etm.2017.5542
84. Georgescu S-R, Tampa M, Caruntu C, Sarbu M-I, Mitran C-I, Mitran M-I, et al. Advances in understanding the immunological pathways in psoriasis. Int J Mol Sci. (2019) 20:739. doi: 10.3390/ijms20030739
85. Ren S-J, Liu T, Xu M-H, Shi W, and Li X-R. Inflammatory bowel disease and risk of ophthalmic inflammation-related diseases: A two-sample Mendelian randomization study. Int J Ophthalmol. (2024) 17:2100–8. doi: 10.18240/ijo.2024.11.17
86. Songel-Sanchis B and Cosín-Roger J. Analysis of the incidence of ocular extraintestinal manifestations in inflammatory bowel disease patients: A systematic review. Diagnostics. (2024) 14:2815. doi: 10.3390/diagnostics14242815
87. Ingold CJ, Sathe NC, and Khan MA. Pemphigus Vulgaris. (2025). In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing.
88. Geng RSQ, Wilken B, Sood S, Sibbald RG, and Sibbald C. Biomarkers in pemphigus vulgaris: A systematic review. J Cutan Med Surg. (2024) 28:458–62. doi: 10.1177/12034754241266136
89. R H, Ramani P, Tilakaratne W, Sukumaran G, Ramasubramanian A, and Krishnan RP. Critical appraisal of different triggering pathways for the pathobiology of pemphigus vulgaris—A review. Oral Dis. (2022) 28:1760–9. doi: 10.1111/odi.13937
90. Kaur B, Kerbrat J, Kho J, Kaler M, Kanatsios S, and Cirillo N. Mechanism-based therapeutic targets of pemphigus vulgaris: A scoping review of pathogenic molecular pathways. Exp Dermatol. (2022) 31:154–71. doi: 10.1111/exd.14453
91. Rahimi S, Hariton WVJ, Khalaj F, Ludwig RJ, Borradori L, and Müller EJ. Desmoglein-driven dynamic signaling in pemphigus vulgaris: A systematic review of pathogenic pathways. NPJ Regen Med. (2025) 10:39. doi: 10.1038/s41536-025-00426-x
92. Hammers CM, Schmidt E, and Borradori L. Pemphigus vegetans. In: European Handbook of Dermatological Treatments. Springer International Publishing, Cham (2023). p. 739–43. doi: 10.1007/978-3-031-15130-9_68
93. Messersmith L and Krauland K. Pemphigus Vegetans. (2025). In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing.
94. Hocking AM and Buckner JH. Genetic basis of defects in immune tolerance underlying the development of autoimmunity. Front Immunol. (2022) 13:972121. doi: 10.3389/fimmu.2022.972121
95. Sharkey P and Thomas R. Immune tolerance therapies for autoimmune diseases: shifting the goalpost to cure. Curr Opin Pharmacol. (2022) 65:102242. doi: 10.1016/j.coph.2022.102242
96. Kim CH. Complex regulatory effects of gut microbial short-chain fatty acids on immune tolerance and autoimmunity. Cell Mol Immunol. (2023) 20:341–50. doi: 10.1038/s41423-023-00987-1
97. Shirafkan F, Hensel L, and Rattay K. Immune tolerance and the prevention of autoimmune diseases essentially depend on thymic tissue homeostasis. Front Immunol. (2024) 15:1339714. doi: 10.3389/fimmu.2024.1339714
98. Valdes AZ. Immunological tolerance and autoimmunity. In: Translational Autoimmunity. Elsevier (2022). p. 325–45. doi: 10.1016/B978-0-12-822564-6.00009-4
99. Wixler V, Zaytsev IZ, Leite Dantas R, Schied T, Boergeling Y, Lührmann V, et al. Small spleen peptides prevent development of psoriatic arthritis via restoration of peripheral tolerance. Mol Ther. (2022) 30:745–62. doi: 10.1016/j.ymthe.2021.08.030
100. Sai A, Shetty GB, Shetty P, and H L N. Influence of gut microbiota on autoimmunity: A narrative review. Brain Behav Immun Integr. (2024) 5:100046. doi: 10.1016/j.bbii.2024.100046
101. Lamba A and Taneja V. Gut microbiota as a sensor of autoimmune response and treatment for rheumatoid arthritis. Immunol Rev. (2024) 325:90–106. doi: 10.1111/imr.13359
102. Bhutta NK, Xu X, Jian C, Wang Y, Liu Y, Sun J, et al. Gut microbiota mediated T cells regulation and autoimmune diseases. Front Microbiol. (2024) 15:1477187. doi: 10.3389/fmicb.2024.1477187
103. Sadeghpour Heravi F. Gut microbiota and autoimmune diseases: mechanisms, treatment, challenges, and future recommendations. Curr Clin Microbiol Rep. (2024) 11:18–33. doi: 10.1007/s40588-023-00213-6
104. He L, Li X, Jiang S, Ou Y, Wang S, Shi N, et al. The influence of the gut microbiota on B cells in autoimmune diseases. Mol Med. (2025) 31:149. doi: 10.1186/s10020-025-01195-5
105. Zhang Y, Peng Y, and Xia X. Autoimmune diseases and gut microbiota: A bibliometric and visual analysis from 2004 to 2022. Clin Exp Med. (2023) 23:2813–27. doi: 10.1007/s10238-023-01028-x
106. Xu Q, Ni J-J, Han B-X, Yan S-S, Wei X-T, Feng G-J, et al. Causal relationship between gut microbiota and autoimmune diseases: A two-sample Mendelian randomization study. Front Immunol. (2022) 12:746998. doi: 10.3389/fimmu.2021.746998
107. Piccioni A, Cicchinelli S, Valletta F, De Luca G, Longhitano Y, Candelli M, et al. Gut microbiota and autoimmune diseases: A charming real world together with probiotics. Curr Med Chem. (2022) 29:3147–59. doi: 10.2174/0929867328666210922161913
108. Wang Q, Lu Q, Jia S, and Zhao M. Gut immune microenvironment and autoimmunity. Int Immunopharmacol. (2023) 124:110842. doi: 10.1016/j.intimp.2023.110842
109. Zeng L, Yang K, He Q, Zhu X, Long Z, Wu Y, et al. Efficacy and safety of gut microbiota-based therapies in autoimmune and rheumatic diseases: A systematic review and meta-analysis of 80 randomized controlled trials. BMC Med. (2024) 22:110. doi: 10.1186/s12916-024-03303-4
110. Choi S-C, Brown J, Gong M, Ge Y, Zadeh M, Li W, et al. Gut microbiota dysbiosis and altered tryptophan catabolism contribute to autoimmunity in lupus-susceptible mice. Sci Transl Med. (2020) 12(551):eaax2220. doi: 10.1126/scitranslmed.aax2220
111. Ma Y, Xu X, Li M, Cai J, Wei Q, and Niu H. Gut microbiota promote the inflammatory response in the pathogenesis of systemic lupus erythematosus. Mol Med. (2019) 25:35. doi: 10.1186/s10020-019-0102-5
112. Zheng S-J, Luo Y, Wang J-B, Chen X-M, Xu Y, and Xiao J-H. Regulated intestinal microbiota and gut immunity to ameliorate type 1 diabetes mellitus: A novel mechanism for stem cell-based therapy. Biomed Pharmacother. (2024) 170:116033. doi: 10.1016/j.biopha.2023.116033
113. Knip M and Siljander H. The role of the intestinal microbiota in type 1 diabetes mellitus. Nat Rev Endocrinol. (2016) 12:154–67. doi: 10.1038/nrendo.2015.218
114. Zhang J, Hoedt EC, Liu Q, Berendsen E, Teh JJ, Hamilton A, et al. Elucidation of proteus mirabilis as a key bacterium in Crohn’s disease inflammation. Gastroenterology. (2021) 160:317–30.e11. doi: 10.1053/j.gastro.2020.09.036
115. Alesa D, Alshamrani H, Alzahrani Y, Alamssi D, Alzahrani N, and Almohammadi M. The role of gut microbiome in the pathogenesis of psoriasis and the therapeutic effects of probiotics. J Fam Med Prim Care. (2019) 8:3496. doi: 10.4103/jfmpc.jfmpc_709_19
116. Xiao Y, Wang Y, Tong B, Gu Y, Zhou X, Zhu N, et al. Eubacterium rectale is a potential marker of altered gut microbiota in psoriasis and psoriatic arthritis. Microbiol Spectr. (2024) 12(4):e0115423. doi: 10.1128/spectrum.01154-23
117. Hidalgo-Cantabrana C, Gómez J, Delgado S, Requena-López S, Queiro-Silva R, Margolles A, et al. Gut microbiota dysbiosis in a cohort of patients with psoriasis. Br J Dermatol. (2019) 181:1287–95. doi: 10.1111/bjd.17931
118. Li R, Meng X, Chen B, Zhao L, and Zhang X. Gut microbiota in lupus: A butterfly effect? Curr Rheumatol Rep. (2021) 23:27. doi: 10.1007/s11926-021-00986-z
119. Kim J-W, Kwok S-K, Choe J-Y, and Park S-H. Recent advances in our understanding of the link between the intestinal microbiota and systemic lupus erythematosus. Int J Mol Sci. (2019) 20:4871. doi: 10.3390/ijms20194871
120. Jiang L, Shang M, Yu S, Liu Y, Zhang H, Zhou Y, et al. A high-fiber diet synergizes with prevotella copri and exacerbates rheumatoid arthritis. Cell Mol Immunol. (2022) 19:1414–24. doi: 10.1038/s41423-022-00934-6
121. Horta-Baas G, Romero-Figueroa MdS, Montiel-Jarquín AJ, Pizano-Zárate ML, García-Mena J, and Ramírez-Durán N. Intestinal dysbiosis and rheumatoid arthritis: A link between gut microbiota and the pathogenesis of rheumatoid arthritis. J Immunol Res. (2017) 2017:1–13. doi: 10.1155/2017/4835189
122. Guerreiro CS, Calado Â, Sousa J, and Fonseca JE. Diet, microbiota, and gut permeability—The unknown triad in rheumatoid arthritis. Front Med. (2018) 5:349. doi: 10.3389/fmed.2018.00349
123. Schaefer L, Trujillo-Vargas CM, Midani FS, Pflugfelder SC, Britton RA, and de Paiva CS. Gut microbiota from Sjögren syndrome patients causes decreased T regulatory cells in the lymphoid organs and desiccation-induced corneal barrier disruption in mice. Front Med. (2022) 9:852918. doi: 10.3389/fmed.2022.852918
124. Mandl T, Marsal J, Olsson P, Ohlsson B, and Andréasson K. Severe intestinal dysbiosis is prevalent in primary Sjögren’s syndrome and is associated with systemic disease activity. Arthritis Res Ther. (2017) 19:237. doi: 10.1186/s13075-017-1446-2
125. van der Meulen TA, Harmsen HJM, Vila AV, Kurilshikov A, Liefers SC, Zhernakova A, et al. Shared gut, but distinct oral microbiota composition in primary Sjögren’s syndrome and systemic lupus erythematosus. J Autoimmun. (2019) 97:77–87. doi: 10.1016/j.jaut.2018.10.009
126. Bostick JW, Schonhoff AM, and Mazmanian SK. Gut microbiome-mediated regulation of neuroinflammation. Curr Opin Immunol. (2022) 76:102177. doi: 10.1016/j.coi.2022.102177
127. Anis E, Xie A, Brundin L, and Brundin P. Digesting recent findings: gut alpha-synuclein, microbiome changes in Parkinson’s disease. Trends Endocrinol Metab. (2022) 33:147–57. doi: 10.1016/j.tem.2021.11.005
128. Hirayama M and Ohno K. Parkinson’s disease and gut microbiota. Ann Nutr Metab. (2021) 77:28–35. doi: 10.1159/000518147
129. Engen PA, Dodiya HB, Naqib A, Forsyth CB, Green SJ, Voigt RM, et al. The potential role of gut-derived inflammation in multiple system atrophy. J Park Dis. (2017) 7:331–46. doi: 10.3233/JPD-160991
130. Motofei IG. Melanoma and autoimmunity: spontaneous regressions as a possible model for new therapeutic approaches. Melanoma Res. (2019) 29:231–6. doi: 10.1097/CMR.0000000000000573
131. Motofei IG. Malignant melanoma: autoimmunity and supracellular messaging as new therapeutic approaches. Curr Treat Options Oncol. (2019) 20:45. doi: 10.1007/s11864-019-0643-4
132. Ohta S, Misawa A, Kyi-Tha-Thu C, Matsumoto N, Hirose Y, and Kawakami Y. Melanoma antigens recognized by T cells and their use for immunotherapy. Exp Dermatol. (2023) 32:297–305. doi: 10.1111/exd.14741
133. Caraviello C, Nazzaro G, Tavoletti G, Boggio F, Denaro N, Murgia G, et al. Melanoma skin cancer: A comprehensive review of current knowledge. Cancers (Basel). (2025) 17:2920. doi: 10.3390/cancers17172920
134. Long GV, Swetter SM, Menzies AM, Gershenwald JE, and Scolyer RA. Cutaneous melanoma. Lancet. (2023) 402:485–502. doi: 10.1016/S0140-6736(23)00821-8
135. Centeno PP, Pavet V, and Marais R. The journey from melanocytes to melanoma. Nat Rev Cancer. (2023) 23:372–90. doi: 10.1038/s41568-023-00565-7
136. Ostrowski SM and Fisher DE. Biology of melanoma. Hematol Oncol Clin North Am. (2021) 35:29–56. doi: 10.1016/j.hoc.2020.08.010
137. Caruntu C. Catecholamines increase in vitro proliferation of murine B16F10 melanoma cells. Acta Endocrinol. (2014) 10:545–58. doi: 10.4183/aeb.2014.545
138. Surcel M, Constantin C, Caruntu C, Zurac S, and Neagu M. Inflammatory cytokine pattern is sex-dependent in mouse cutaneous melanoma experimental model. J Immunol Res. (2017) 2017:1–10. doi: 10.1155/2017/9212134
139. Scheau C, Draghici C, Ilie MA, Lupu M, Solomon I, Tampa M, et al. Neuroendocrine factors in melanoma pathogenesis. Cancers (Basel). (2021) 13:2277. doi: 10.3390/cancers13092277
140. Dobre E-G, Surcel M, Constantin C, Ilie MA, Caruntu A, Caruntu C, et al. Skin cancer pathobiology at a glance: A focus on imaging techniques and their potential for improved diagnosis and surveillance in clinical cohorts. Int J Mol Sci. (2023) 24:1079. doi: 10.3390/ijms24021079
141. Teulings HE, Overkamp M, Ceylan E, Nieuweboer-Krobotova L, Bos JD, Nijsten T, et al. Decreased risk of melanoma and nonmelanoma skin cancer in patients with vitiligo: A survey among 1307 patients and their partners. Br J Dermatol. (2013) 168:162–71. doi: 10.1111/bjd.12111
142. Paradisi A, Tabolli S, Didona B, Sobrino L, Russo N, and Abeni D. Markedly reduced incidence of melanoma and nonmelanoma skin cancer in a nonconcurrent cohort of 10,040 patients with vitiligo. J Am Acad Dermatol. (2014) 71:1110–6. doi: 10.1016/j.jaad.2014.07.050
143. Teulings H-E, Limpens J, Jansen SN, Zwinderman AH, Reitsma JB, Spuls PI, et al. Vitiligo-like depigmentation in patients with stage III-IV melanoma receiving immunotherapy and its association with survival: A systematic review and meta-analysis. J Clin Oncol. (2015) 33:773–81. doi: 10.1200/JCO.2014.57.4756
144. Hua C, Boussemart L, Mateus C, Routier E, Boutros C, Cazenave H, et al. Association of vitiligo with tumor response in patients with metastatic melanoma treated with pembrolizumab. JAMA Dermatol. (2016) 152:45. doi: 10.1001/jamadermatol.2015.2707
145. Lancieri M, Bustaffa M, Palmeri S, Prigione I, Penco F, Papa R, et al. An update on familial mediterranean fever. Int J Mol Sci. (2023) 24:9584. doi: 10.3390/ijms24119584
146. Ozen S. Update in familial Mediterranean fever. Curr Opin Rheumatol. (2021) 33:398–402. doi: 10.1097/BOR.0000000000000821
147. Feng S, Tang D, Wang Y, Li X, Bao H, Tang C, et al. The mechanism of ferroptosis and its related diseases. Mol Biomed. (2023) 4:33. doi: 10.1186/s43556-023-00142-2
148. Dixon SJ and Olzmann JA. The cell biology of ferroptosis. Nat Rev Mol Cell Biol. (2024) 25:424–42. doi: 10.1038/s41580-024-00703-5
149. Ma C, Li H, Lu S, and Li X. Thyroid-associated ophthalmopathy and ferroptosis: A review of pathological mechanisms and therapeutic strategies. Front Immunol. (2024) 15:1475923. doi: 10.3389/fimmu.2024.1475923
150. Chen S, Diao J, Yue Z, and Wei R. Identification and validation of ferroptosis-related genes and immune cell infiltration in thyroid associated ophthalmopathy. Front Genet. (2023) 14:1118391. doi: 10.3389/fgene.2023.1118391
151. Stamellou E, Seikrit C, Tang SCW, Boor P, Tesař V, Floege J, et al. IgA nephropathy. Nat Rev Dis Prim. (2023) 9:67. doi: 10.1038/s41572-023-00476-9
152. Pitcher D, Braddon F, Hendry B, Mercer A, Osmaston K, Saleem MA, et al. Long-term outcomes in IgA nephropathy. Clin J Am Soc Nephrol. (2023) 18:727–38. doi: 10.2215/CJN.0000000000000135
153. Cheung CK, Alexander S, Reich HN, Selvaskandan H, Zhang H, and Barratt J. The pathogenesis of IgA nephropathy and implications for treatment. Nat Rev Nephrol. (2025) 21:9–23. doi: 10.1038/s41581-024-00885-3
154. Sánchez-Agesta M, Rabasco C, Soler MJ, Shabaka A, Canllavi E, Fernández SJ, et al. Anti-glomerular basement membrane glomerulonephritis: A study in real life. Front Med. (2022) 9:889185. doi: 10.3389/fmed.2022.889185
155. Caillard P, Vigneau C, Halimi J-M, Hazzan M, Thervet E, Heitz M, et al. Prognostic value of complement serum C3 level and glomerular C3 deposits in anti-glomerular basement membrane disease. Front Immunol. (2023) 14:1190394. doi: 10.3389/fimmu.2023.1190394
156. Zhu M, Wang J, Le W, Xu F, Jin Y, Jiao C, et al. Relationship between serum complement C3 levels and outcomes among patients with anti-GBM disease. Front Immunol. (2022) 13:929155. doi: 10.3389/fimmu.2022.929155
157. Hu S, Jia X, Yang X, Yu F, Cui Z, and Zhao M. Glomerular C1q deposition and serum anti-C1q antibodies in anti-glomerular basement membrane disease. BMC Immunol. (2013) 14:42. doi: 10.1186/1471-2172-14-42
158. Ma R, Cui Z, Hu S-Y, Jia X-Y, Yang R, Zheng X, et al. The alternative pathway of complement activation may be involved in the renal damage of human anti-glomerular basement membrane disease. PLoS One. (2014) 9:e91250. doi: 10.1371/journal.pone.0091250
159. Nithagon P, Cortazar F, Shah SI, Weins A, Laliberte K, Jeyabalan A, et al. Eculizumab and complement activation in anti–glomerular basement membrane disease. Kidney Int Rep. (2021) 6:2713–7. doi: 10.1016/j.ekir.2021.07.001
160. Ellebrecht CT, Bhoj VG, Nace A, Choi EJ, Mao X, Cho MJ, et al. Reengineering chimeric antigen receptor T cells for targeted therapy of autoimmune disease. Sci (80-.). (2016) 353:179–84. doi: 10.1126/science.aaf6756
Keywords: autoimmune diseases, autoantibodies, immunoregulatory proteins, biomarkers, diagnosis, immunomodulatory therapies
Citation: Neagu M, Ilie MA, Mihai A and Caruntu C (2025) Editorial: Autoimmunity: novel insights and future perspectives. Front. Immunol. 16:1728233. doi: 10.3389/fimmu.2025.1728233
Received: 19 October 2025; Accepted: 23 October 2025;
Published: 31 October 2025.
Edited and reviewed by:
Betty Diamond, Feinstein Institute for Medical Research, United StatesCopyright © 2025 Neagu, Ilie, Mihai and Caruntu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
*Correspondence: Constantin Caruntu, Y29zdGluLmNhcnVudHVAZ21haWwuY29t; Monica Neagu, bmVhZ3UubW9uaWNhQGdtYWlsLmNvbQ==; Mihaela Adriana Ilie, bWloYWVsYWFkcmlhbmEyMDA1QHlhaG9vLmNvbQ==; Ancuta Mihai, Y29jYS5hbmN1dGFAZ21haWwuY29t