Autoimmune response in cartilage-delivered peptides in a patient with osteoarthritis

Abstract

Whatever the initiating factor of osteoarthritis (OA), the process ultimately unmasks the immunogenic determinants of chondrocytes, proteoglycans and collagens, which then triggers autoimmune reactions. Although the precise mechanism of the immune responses in the pathogenesis of OA requires further investigation, here I postulate that the presence of autoimmunity to cartilage components has an important role in the process of cartilage degradation in OA. Current studies strongly suggest that a immunoregulatory therapeutic strategy should be established.

Introduction

My colleagues and I have recently reported several lines of evidence for a potential role of immunological intervention in the pathogenic process of osteoarthritis (OA). In particular, we have focused on the role of activated T cells [1] after an immunological response to the cartilage component [2-4] with activation by chemokines [5,6]. The background of this concept comes from a pathological feature of OA synovium. Although OA is generally accepted as one of the commonest degenerative joint disorders caused by biomechanical stress or aging, instances of inflammatory features such as synovial effusion or swelling of affected joints have been reported. The accumulation of mononuclear cells in synovial fluid, an increasing concentration of immunoglobulin and pathological findings of OA synovial tissue such as hyperplasia of synovial lining cells and infiltration of inflammatory cells into the sublining layer strongly suggest chronic inflammatory features of OA. These findings resemble the early stage of rheumatoid arthritis [7-9]. We were therefore interested in the immune response to cartilage components such as cartilage intermediate layer protein (CILP) and YKL39 [10,11]. In particular, endogenous articular cartilage components have been found to provide a rich source of antigenic determinants in OA.

We previously detected CD3 T cells in the synovium tissue and CD4⁺CD8⁺ cells in the sublining layer in OA. Moreover, the number of interferon-γ-bearing T cells was fivefold that of IL-4-positive cells. In addition, we identified clonal diversity in the infiltrated T cells [1]. These findings of oligoclonal T cell expansion in OA synovium and the presence of T cell aggregates undergoing in situ activation in a rather specific manner indicate that a Th1 cell-mediated specific immune response might be taking place in OA synovium, driven by local antigens.

Why should T cells have a potential role in the pathogenic process of cartilage destruction in OA? Current work suggests that extracellular matrix-filling material hyaluronan can modulate the function of antigen-presenting cells in monocytes. Recent studies show that dendritic cells and T cells constitutionally express genes involved in hyaluronan synthesis (HAS1 and HAS3) and encoding hyaluronidase, Hyal3 [12]. After the secretion of hyaluron-degrading enzymes, dendritic cells and T cells need to detach from the extracellular matrix to migrate from or to lymph nodes. Either way, an involvement of the T cell activation process in joints is strongly associated with turnover of extracellular hyaluronan.

In conclusion, I would like to emphasize that examining the potential role of T cells and autoantibody against cartilage components in OA has been instrumental in developing not only new insights into the pathogenesis of OA but also novel strategies for the treatment of OA, such as the application of an immunomodulative agent.

Competing interests

None declared.

Abbreviations

OA = osteoarthritis.