Research Topic

Recent Advances in Potential Biomarkers for Rheumatic Diseases and in Cell-based Therapies in the Management of Inflammatory Rheumatic Diseases

About this Research Topic


Inflammatory rheumatic diseases (IRD) constitute a wide spectrum of disorders encompassing inflammatory arthropathies, including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS). It also includes connective tissue disorders, such as systemic lupus erythematosus (SLE), Sjögren's syndrome (SS) or systemic sclerosis (SSc). This highly heterogeneous group of conditions has multifactorial and not fully understood etiology and is characterized by the presence of persistent inflammation affecting primarily the musculoskeletal system and connective tissue. Disease progression ultimately leads to functional disability, premature mortality, as well as economic and social burdens. Rheumatoid arthritis and spondyloarthritis represent the most common inflammatory rheumatic diseases. The management of RA and other forms of IRD has dramatically changed in the last 20 years with the development of targeted therapeutic agents, namely biological disease modifying anti-rheumatic drugs (bDMARDs) and targeted synthetic disease modifying anti-rheumatic drugs (tsDMARDs). However, a substantial proportion of patients still exhibits an inadequate response, do not achieve remission, or develop side effects.

Biomarkers constitute a powerful approach to the diagnosis and management of rheumatic diseases. Rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPAs) are the most well-established markers for RA diagnosis and prognosis. The presence of antinuclear antibodies (ANAs) – that are directed against intracellular antigens – is the hallmark of SLE. On the other hand, one of the most significant genetic markers for rheumatic diseases is human leukocyte antigen HLA-B27 allele, which is strongly associated with AS.

In recent years, a novel multi-biomarker disease activity (MBDA) test for disease activity assessment in RA patients has been developed and implemented into clinical practice. This blood-based test measures the levels of 12 serum proteins: interleukin-6 (IL-6), tumor necrosis factor receptor type I (TNFRI), vascular cell adhesion molecule 1 (VCAM-1), epidermal growth factor (EGF), vascular endothelial growth factor A (VEGF-A), glycoprotein YKL-40, matrix metalloproteinase 1 (MMP-1), MMP-3, C-reactive protein (CRP), serum amyloid A (SAA), leptin, and resistin. A composite MBDA score is calculated from a combination of these measures.

Rapid progress in molecular biology during the last two decades has resulted in developments in the field of biomarker research. These advances can lead to the improvement of disease prevention and early detection, as well as significant progress in the assessment of disease activity or prognosis for individual patients. Furthermore, biomarkers can be used as powerful tools to predict the response to therapy, establish the optimal therapeutic dose, and monitor the treatment’s efficacy. This progress can also be applied to develop new therapeutic approaches, such as cell-based therapies.

Cell therapy is one therapeutic approach of IRD, based on the administration of cells that can control the immune deregulation, inflammatory cytokine production and overall systemic inflammation. This can ultimately prevent joint damage. A large body of clinical research has helped to describe the potential immune-modulating properties and regenerative potential of cell-based therapies. Several immune regulatory cell types have been defined as potential candidates for cell therapy, including mesenchymal stroma cells (derived from the bone marrow, the adipose tissue, the synovium or the umbilical cord), dendritic cells, regulatory T cells, apoptotic cells and induced pluripotent stem (iPS) cells.

This Research Topic focuses on recent advances in the identification of diagnostic, prognostic and predictive biomarkers for IRD, as well as recent advances in cell-based therapies in the treatment of RA and other forms of arthritis. Concerning cell-based therapies, manuscripts dealing with the characterisation of the cellular source, the biological and immunological properties of cell therapies and the evidences of their potential interest in the treatment of IRD are welcome. Manuscripts on gene-modified cells (e.g., chimeric antigen receptors) or CRISPR/Cas 9 genome-engineered cells are also welcome.

We welcome authors to submit Original Research, Systematic Review, Review, Mini Review, Perspective and Brief Research Report articles focusing on, but not limited to:
• New findings in the biomarkers field for IRD including genomic, transcriptomic, proteomic and metabolomic biomarkers
• Characterisation of the cellular source, the biological and immunological properties of cell therapies and the evidence of their potential interest in the treatment of IRD


Prof. Saas is the author of a patent and a shareholder of Med’Inn’Pharma, related to the development of anti-inflammatory treatment


Keywords: IRD, spondyloarthritis, rheumatoid arthritis, biomarkers, cell-based therapy


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.


Inflammatory rheumatic diseases (IRD) constitute a wide spectrum of disorders encompassing inflammatory arthropathies, including rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS). It also includes connective tissue disorders, such as systemic lupus erythematosus (SLE), Sjögren's syndrome (SS) or systemic sclerosis (SSc). This highly heterogeneous group of conditions has multifactorial and not fully understood etiology and is characterized by the presence of persistent inflammation affecting primarily the musculoskeletal system and connective tissue. Disease progression ultimately leads to functional disability, premature mortality, as well as economic and social burdens. Rheumatoid arthritis and spondyloarthritis represent the most common inflammatory rheumatic diseases. The management of RA and other forms of IRD has dramatically changed in the last 20 years with the development of targeted therapeutic agents, namely biological disease modifying anti-rheumatic drugs (bDMARDs) and targeted synthetic disease modifying anti-rheumatic drugs (tsDMARDs). However, a substantial proportion of patients still exhibits an inadequate response, do not achieve remission, or develop side effects.

Biomarkers constitute a powerful approach to the diagnosis and management of rheumatic diseases. Rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACPAs) are the most well-established markers for RA diagnosis and prognosis. The presence of antinuclear antibodies (ANAs) – that are directed against intracellular antigens – is the hallmark of SLE. On the other hand, one of the most significant genetic markers for rheumatic diseases is human leukocyte antigen HLA-B27 allele, which is strongly associated with AS.

In recent years, a novel multi-biomarker disease activity (MBDA) test for disease activity assessment in RA patients has been developed and implemented into clinical practice. This blood-based test measures the levels of 12 serum proteins: interleukin-6 (IL-6), tumor necrosis factor receptor type I (TNFRI), vascular cell adhesion molecule 1 (VCAM-1), epidermal growth factor (EGF), vascular endothelial growth factor A (VEGF-A), glycoprotein YKL-40, matrix metalloproteinase 1 (MMP-1), MMP-3, C-reactive protein (CRP), serum amyloid A (SAA), leptin, and resistin. A composite MBDA score is calculated from a combination of these measures.

Rapid progress in molecular biology during the last two decades has resulted in developments in the field of biomarker research. These advances can lead to the improvement of disease prevention and early detection, as well as significant progress in the assessment of disease activity or prognosis for individual patients. Furthermore, biomarkers can be used as powerful tools to predict the response to therapy, establish the optimal therapeutic dose, and monitor the treatment’s efficacy. This progress can also be applied to develop new therapeutic approaches, such as cell-based therapies.

Cell therapy is one therapeutic approach of IRD, based on the administration of cells that can control the immune deregulation, inflammatory cytokine production and overall systemic inflammation. This can ultimately prevent joint damage. A large body of clinical research has helped to describe the potential immune-modulating properties and regenerative potential of cell-based therapies. Several immune regulatory cell types have been defined as potential candidates for cell therapy, including mesenchymal stroma cells (derived from the bone marrow, the adipose tissue, the synovium or the umbilical cord), dendritic cells, regulatory T cells, apoptotic cells and induced pluripotent stem (iPS) cells.

This Research Topic focuses on recent advances in the identification of diagnostic, prognostic and predictive biomarkers for IRD, as well as recent advances in cell-based therapies in the treatment of RA and other forms of arthritis. Concerning cell-based therapies, manuscripts dealing with the characterisation of the cellular source, the biological and immunological properties of cell therapies and the evidences of their potential interest in the treatment of IRD are welcome. Manuscripts on gene-modified cells (e.g., chimeric antigen receptors) or CRISPR/Cas 9 genome-engineered cells are also welcome.

We welcome authors to submit Original Research, Systematic Review, Review, Mini Review, Perspective and Brief Research Report articles focusing on, but not limited to:
• New findings in the biomarkers field for IRD including genomic, transcriptomic, proteomic and metabolomic biomarkers
• Characterisation of the cellular source, the biological and immunological properties of cell therapies and the evidence of their potential interest in the treatment of IRD


Prof. Saas is the author of a patent and a shareholder of Med’Inn’Pharma, related to the development of anti-inflammatory treatment


Keywords: IRD, spondyloarthritis, rheumatoid arthritis, biomarkers, cell-based therapy


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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Submission Deadlines

24 July 2020 Abstract
20 November 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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Topic Editors

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Submission Deadlines

24 July 2020 Abstract
20 November 2020 Manuscript

Participating Journals

Manuscripts can be submitted to this Research Topic via the following journals:

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