Autoantibodies Associated With Connective Tissue Diseases: What Meaning for Clinicians?

Abstract

Connective tissue diseases (CTDs) such as systemic lupus erythematosus, systemic sclerosis, myositis, Sjögren's syndrome, and rheumatoid arthritis are systemic diseases which are often associated with a challenge in diagnosis. Autoantibodies (AAbs) can be detected in these diseases and help clinicians in their diagnosis. Actually, pathophysiology of these diseases is associated with the presence of antinuclear antibodies. In the last decades, many new antibodies were discovered, but their implication in pathogenesis of CTDs remains unclear. Furthermore, the classification of these AAbs is nowadays misused, as their targets can be localized outside of the nuclear compartment. Interestingly, in most cases, each antibody is associated with a specific phenotype in CTDs and therefore help in better defining either the disease subtypes or diseases activity and outcome. Because of recent progresses in their detection and in the comprehension of their pathogenesis implication in CTD-associated antibodies, clinicians should pay attention to the presence of these different AAbs to improve patient's management. In this review, we propose to focus on the different phenotypes and features associated with each autoantibody used in clinical practice in those CTDs.

Keywords: Sjögren’s syndrome; antibody; antisynthetase syndrome; dermatomyositis; necrotizing myopathy; rheumatoid arthritis; systemic lupus erythematosus; systemic sclerosis.

Figure 1

Global vision of autoantigens targeted by autoantibody (AAb) according to the type of connective tissue diseases (CTDs). The main targets of AAb associated with the five CTDs detailed in this review are recapitulated on this figure. In myositis, four distinct forms associated with distinct AAbs are represented in dotted circles: antisynthetase syndrome (ASS), dermatomyositis (DM), necrotizing myopathy (NM), and inclusion body myositis (IBM). In systemic sclerosis (SSc), most AAbs are preferentially associated with one of the two cutaneous forms described: anti-centromere, anti-Th/To, anti-Pm/Scl, anti-Ku, and anti-U1-RNP AAbs are generally associated with limited form of SSc whereas anti-DNA-topoisomerase I, anti-RNA-polymerase III, and anti-U3-RNP AAbs are mostly associated with diffuse cutaneous SSc. The term ACPA regroups anti-cyclic citrullinated peptide and also anti-non-cyclic citrullinated peptides AAb. Fc of IgG corresponds to target of rheumatoid factor. Some AAbs are associated with more than one CTD as shown in the different overlap areas on the figure.