Editorial: Immune Monitoring Responses in Renal Autoimmune Diseases

1 Center of Expertise for Lupus-, Vasculitisand Complement-Mediated Systemic Autoimmune Diseases, Department of Internal Medicine—Nephrology Section, Leiden University Medical Center, Leiden, Netherlands, 2 Centre for Inflammatory Disease, Department of Immunology and Inflammation, Imperial College London, Hammersmith Hospital, London, United Kingdom, 3 Department of Biomedical, Experimental and Clinical Sciences “Mario Serio”, University of Firenze, and Nephrology and Dialysis Unit, Meyer Children’s Hospital, Firenze, Italy, 4 Division of Rheumatology, Department of Medicine, Tuen Mun Hospital, Hong Kong, Hong Kong

anti-dsDNA antibodies can be accepted as a clinical biomarker for SLE, without clarifying what we define as an anti-dsDNA antibody, and in which biologic contexts these antibodies appear.
The group of Wu et al. addressed the epitope spreading of anti-C1q autoantibodies in LN with regard to the "anti-C1q A08 antibodies". These are part of the anti-C1q antibody family, which recognize nearly complete cryptic epitope in ELISA. Of note, these anti-C1q antibodies recognize the exposed epitope of C1q coated on an ELISA plate. C1q A08 was demonstrated to be important for activation of classical complement pathway and is an important contributor to pathologically relevant anti-C1q antibodies in LN.
The group of Hong et al. provided an overview of the recent advances in our understanding of renal tubular epithelial cells in LN, and the potential role of tubular epithelial cells as biomarkers in the diagnosis, prognosis, and treatment of LN, as well as the future therapeutic potential of targeting the tubulointerstitium for the treatment of patients with LN. In line with this review, several newly identified urine biomarkers, including monocyte chemoattractant protein-1 (MCP-1), neutrophil gelatinase associated lipocalin (NGAL), TNF-like WEAK inducer of apoptosis (TWEAK), and vascular cell adhesion molecule-1 (VCAM), are proteins that may arise directly from inflamed kidneys and have been promising in monitoring LN disease status. In this Research Topic, the group of Zhang et al. demonstrated that the urinary biomarker sCD163 outperformed C3, C4, urinary protein-tocreatinine ratio, or anti-dsDNA antibody in discriminating nonproliferative LN class II or V from proliferative LN class III or IV. A promising finding that can help identifying active LN patients in whom a renal biopsy could be avoided.
Lastly Lastly, the group of Huang et al. demonstrated anti-PLA2R autoantibodies in patients with autoimmune thyroid disease, notably Hashimoto hypothyroiditis, which is associated with proteinuric AutoImmune Thyroid Disease (AITD) associated nephropathy in 10% of the cases. Given the commonality of anti-PLA2R autoantibodies in these overlapping disease, this common pathologic substrate may help identifying those patients that could profit from immunosuppressive or B-cell targeted therapies. With respect to CMDs, the group of Gao et al. reviewed the dual roles of the C3a/C3aR interactions, that can exert antiinflammatory or pro-inflammatory effects depending on the type of kidney disease, with the aim of understanding in-depth its controversial roles and its potential therapeutic value.

IMMUNOMONITORING IN ANCA-ASSOCIATED VASCULITIS
Lastly, the group of Ramponi et al. reviewed the current literature to provide guidance on serum biomarkers that could support further testing for kidney involvement in primary Sjögren syndrome (pSS). Patients with pSS typically present with proximal renal tubular acidosis, distal renal tubular acidosis and/or acute (on chronic) kidney impairment for which the most classical kidney lesions are tubulointerstitial nephritis (TIN) and membranoproliferative glomerulonephritis (MPGN).

CONCLUSION
The present Research Topic aims to foster knowledge and discussion on investigating and understanding relevant pathological mechanisms underpinning renal autoimmune diseases. As such, these collective research efforts strengthen our Immuno-nephrology community's capabilities to translating the wealth of data, mostly derived from recent technological advances, into useful discoveries for clinical applicability. Ultimately, the monitoring of the relevant immune phenomena in patients with renal autoimmune diseases will lead to useful intervention to influence disease progression with effective targeted drugs.

AUTHOR CONTRIBUTIONS
YT and CK prepared the manuscript. All authors contributed to the article and approved the submitted version.

FUNDING
The work of YT is supported by the Dutch Kidney Foundation (17OKG04) and the Netherlands Scientific Organisation.