Role of CTHRC1 in Diagnosis of Rheumatoid Arthritis

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Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune disease of synovial joints. Disease progression is characterized by periods of high disease activity involving both, a systemic immune response and tissue-specific inflammatory events that may lead to joint and bone destruction and subs...

Rheumatoid arthritis (RA) is a chronic, progressive, autoimmune disease of synovial joints. Disease progression is characterized by periods of high disease activity involving both, a systemic immune response and tissue-specific inflammatory events that may lead to joint and bone destruction and subsequent disability. Rheumatoid arthritis is a multifactorial disease with significant contribution from genetic and non-genetic factors that together account for complex disease pathology. Diagnosis of RA is based mainly on detection of high titers of rheumatoid factor (RF) and of antibodies against cyclic citrullinated peptide (anti-CCP) or against citrullinated protein (ACPA). The major RF species could be detected only in 60-70% of RA patients; patients with high levels of RF have higher disease activity with greater disabilities. The problem is that RF is not a specific marker for RA and is often absent in early stages of the disease, on the other hand ACPA and CCP auto antibodies provide high specificity but moderate sensitivity, adding to that CRP and ESR are general indicators of inflammation and are not specific for RA. Collagen triple helix repeat containing 1 protein (CTHRC1) is expressed in a number of embryonic and neonate tissues, including developing cartilage and bone. It is a secreted modulator of Wnt signaling, which is a key regulator of joint remodeling and promotes cell proliferation and migration. Immunohistochemical analysis of various human primary cancers and metastases has revealed that CTHRC1 expression is actually limited to the stromal cells of solid tumors. The expression of CTHRC1 encoding gene was found to be strongly associated with the severity of murine collagen antibody-induced arthritis. Arthritic pannus is a multicellular vascularized tissue composed of cells of both mesenchymal and hematopoietic origin, including synovial fibroblasts, osteoclasts, endothelial cells, dendritic cells, monocytes/macrophages, as well as T and B cells that contribute to the development and progression of joint and cartilage erosion through secretion of pro-inflammatory cytokines and tissue-degrading proteases. Fibroblast-like synoviocytes (FLS), particularly the invasive and migratory cadherin-11-positive subtype, are major components of synovial pannus tissue and are considered active drivers in the pathogenesis of RA. The expression of CTHRC1 in pannus and its role in the function of FLS relevant to cartilage damage in RA make it of great value if used as a blood-based biomarker for improved diagnosis of rheumatoid arthritis patients.

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