The concept of a “synovio‐entheseal complex” and its implications for understanding joint inflammation and damage in psoriatic arthritis and beyond

Abstract

The pathogenesis of tissue inflammation and damage in rheumatic diseases that are associated with the major histocompatibility complex (MHC), including rheumatoid arthritis (RA) and the spondylarthritides (SpA), has mainly been viewed in relation to an autoimmune effector mechanism (1–3). However, because synovial joints serve to promote movement, it is logical to assume that aberrant functioning of their constituent parts could contribute to inflammation. Although such “wear and tear” mechanisms are well recognized as contributory factors in osteoarthritis (OA), it is less clear that factors intrinsic to the biomechanical functioning of synovial joints could be significant in diseases considered to be autoimmune. Investigators in our group previously proposed that the primary basis for the pathogenesis of psoriatic arthritis (PsA) and SpA could be biomechanical rather than autoimmune (4–6). This was based on our interpretation of magnetic resonance imaging (MRI) in knee disease in early SpA, which showed specific patterns of inflammation. Moreover, such observations were not confined to SpA, because the anatomic locations of ligaments and tendons also affected both the magnitude of synovitis and the propensity for erosions in early RA (7). This concept of such tissue-specific factors or “autoinflammatory factors” (as distinct from autoimmunity, which is principally played out in the primary and secondary lymphoid organs) allowed for the development of a new classification scheme for all inflammatory disorders (8). Such tissue-specific factors might also underscore common inflammatory or tissue repair pathways that may be shared by both inflammatory and degenerative disorders (9). Thus, the purpose of the present article is to develop the idea that joint-specific factors could trigger innate immune responses and may be pivotal players in the phenotypic expression of PsA, the related SpA, RA, and even OA. The concept is centered on an anatomic unit we have called the synovio-entheseal complex (SEC) and is described in relation to PsA and other types of arthropathy.