Dossier : Rheumatoid arthritis
Autoantibodies in rheumatoid arthritis: a review

https://doi.org/10.1016/j.biopha.2006.09.002Get rights and content

Abstract

Emerging insights into the importance of B cells in the pathogenesis of rheumatoid arthritis (RA) as highlighted by the efficacy of B cell depletion [1] is one factor that has contributed to the upsurge of interest in the potential role of autoantibodies both as disease markers and with respect to a pathogenic role. Since the initial description of rheumatoid factor (RF), a large number of both disease-specific and non-specific autoantibodies have been described in patients with RA including antibodies to type II collagen (CII), immunoglobulin binding protein (BiP) and antibodies directed at citrullinated peptides (anti-CCP) and other citrullinated proteins such as vimentin (anti-Sa) [2]. Despite some overlap the serological profile of RA does appear to be distinct from other diseases such as SLE [2]. Although the precise mechanisms responsible for the formation of these antibodies have not been well defined their presence must reflect the interaction between T and B cells believed to be relevant to the pathogenesis of RA. The specificity of the association of such factors as anti-CCP and anti-BiP with RA may reflect unique pathogenic events leading to the processing and presentation of the “cryptic self” [3]. Ease of measurement and stability make autoantibodies attractive diagnostic and prognostic markers particularly in early disease when it may be difficult to distinguish self-limiting synovitis from persistent disease [4]. The purpose of this article is to provide an overview of the current state of knowledge of the spectrum of autoantibodies thus far characterised in individuals with rheumatoid arthritis, and discuss their diagnostic, prognostic and pathogenetic relevance.

Section snippets

Characterised autoantibody systems in rheumatoid arthritis (RA)

A number of autoantibody systems have now been described in RA and their clinical associations and role as markers of disease examined [2]. Of these only three (rheumatoid factors (RFs), antibodies to citrullinated antigens such as fillagrin and anti-CCP antibody [5], and antibodies to immunoglobulin binding protein (BiP) [6]) have shown sufficient sensitivity and specificity to be considered clinically useful, and only two (RFs and anti-CCP antibody) are used in clinical practice. In this

Autoantibodies as biomarkers in RA

It is clear that the presence of autoantibodies is a feature of RA and despite some overlap the serological profile of RA is distinct from other diseases such as SLE [2]. Many highly specific disease associations with autoantibodies exist and are likely to reflect unique aspects of the pathology in each case [69], [70]. Such autoantibodies have proven to be very important diagnostic markers. Hence it is possible that autoantibodies may be useful diagnostic or prognostic markers in RA especially

Autoantibodies preceding clinical disease onset—a model for the evolution of RA

Several community-based cohort studies have identified autoantibodies in sera of individuals pre-dating the onset of RA. In one of the earliest of such reports, of 30 individuals subsequently developing RA for whom prior sera were available 16 were RF + by latex fixation test, 1/3 of these being positive when the interval between serum collection and disease was greater than 4 years [79]. Similar findings were reported for RFs in the Finland Mini-Health Survey cohort [80] and for AKA [81].

Conclusions

There has been renewed and vigorous interest in the role of B cells in the pathogenesis of RA. Disease-associated antibodies not only provide the potential for valuable biomarkers, but also may allow unique pathogenic insights. A detailed characterisation of the disease-associated autoantibody profiles may allow the rational design of antigen-specific therapies for RA.

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