Elsevier

Autoimmunity Reviews

Volume 15, Issue 7, July 2016, Pages 673-683
Autoimmunity Reviews

Review
Autoantibodies in inflammatory arthritis

https://doi.org/10.1016/j.autrev.2016.03.003Get rights and content

Abstract

Rheumatoid arthritis (RA) is a systemic chronic inflammatory disease characterized by extensive synovitis resulting in erosions of articular cartilage and marginal bone with joint destruction. The lack of immunological tolerance in RA represents the first step toward the development of autoimmunity. Susceptible individuals, under the influence of environmental factors, such as tobacco smoke, and silica exposure, develop autoimmune phenomena that result in the presence of autoantibodies. HLA and non-HLA haplotypes play a major role in determining the development of specific autoantibodies differentiating anti-citrullinated antibodies (ACPA)-positive and negative RA patients. Rheumatoid factor (RF) and ACPA are the serological markers for RA, and during the preclinical immunological phase, autoantibody titers increase with a progressive spread of ACPA antigens repertoire. The presence of ACPA represents an independent risk factor for developing RA in patients with undifferentiated arthritis or arthralgia. Moreover, anti-CarP antibodies have been identified in patients with RA as well as in individuals before the onset of clinical symptoms of RA. Several autoantibodies mainly targeting post-translational modified proteins have been investigated as possible biomarkers to improve the early diagnosis, prognosis and response to therapy in RA patients. Psoriatic arthritis (PsA) is distinguished from RA by infrequent positivity for RF and ACPA, together with other distinctive clinical features. Actually, specific autoantibodies have not been described. Recently, anti-CarP antibodies have been reported in sera from PsA patients with active disease. Further investigations on autoantibodies showing high specificity and sensibility as well as relevant correlation with disease severity, progression, and response to therapy are awaited in inflammatory arthritides.

Section snippets

Mechanisms of autoantibody formation in inflammatory arthritis

Inflammatory arthritis is a group of rheumatologic conditions affecting approximately 3% of the adult population [1]. Rheumatoid arthritis (RA) is the most prevalent inflammatory chronic systemic disease characterized by extensive synovitis and an autoimmune response leading to cartilage and bone erosions with consequent joint destruction [2]. The loss of the immunological tolerance to self-antigens represents the first step toward the development of autoimmune phenomena. Susceptible

Preclinical immunological phase in rheumatoid arthritis

The identification of patients in a preclinical phase may lead to an early diagnosis and a prompt treatment with better disease outcomes. Recent studies have demonstrated the presence of both rheumatoid factor (RF) and ACPA up to 10 years before the onset of RA in the so-called “pre-articular or lymphoid phase” of the disease [58], [59], [60], [61]. The autoantibody titers increase as the onset of disease approach together with a progressive increase of ACPA antigens repertoire, known as epitope

Autoantibodies in undifferentiated arthritis

The term “undifferentiated arthritis” is used to describe those patients with early inflammatory arthritis during the first weeks to months following symptom onset, where it is not possible to establish a specific diagnosis. Many of these patients reach spontaneous remission without need to take a chance to adverse effect of treatment while others will eventually be diagnosed with RA after further evolution of the symptoms and findings [68]. In this contest, it is essential to recognize those

Classical autoantibodies

RF and ACPA are well-known serological markers for RA diagnosis according to the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) classification criteria [80]. RF is present in about 50–80% of patients affected by RA. It has a moderate specificity, around 66%, as it is detected in other autoimmune diseases, systemic infections, and in up to 10% of healthy subjects [81]. Nevertheless, many differences exist between RF in health and disease. The former is an

Autoantibodies in psoriatic arthritis

Psoriatic arthritis (PsA) is a chronic inflammatory arthropathy seronegative for RF, and associated with psoriasis [150]. PsA is classified among the SpA group because it shares with SpA several clinical manifestations as peripheral and axial joints involvement (arthritis, spondylitis, and sacro-ileitis), skin and nail diseases, dactylitis and enthesitis [151]. The overall prevalence of PsA has been reported to range from 0.01% (95% CI 0.00–0.17) in the Middle East to 0.19% (95% CI 0/16–0.32)

Conclusion

Increasing evidence suggests that autoantibodies are associated with inflammatory arthritides including RA and “seronegative” SpA. The well-characterized autoantibodies in RA are RF and ACPA, while other novel antibodies targeting mutated proteins, such as anti-CarP, are extensively under investigation. Autoantibodies appear to improve the early diagnosis in both symptomatic and preclinical patients and may represent a tool to evaluate/predict the response to the therapy. While correlations

Take-home messages

  • In susceptible individuals, under the influence of environmental factors, autoantibodies may be produced in the joints or outside in the mucosal sites such as lung and gingiva.

  • The most relevant autoantibodies in rheumatoid arthritis (RA) appear to be anti-citrullinated peptide antibodies (ACPA) that recognize a variety of post-translational modified proteins, such as filaggrin, fibrinogen, vimentin, type II collagen, alpha enolase, and others.

  • Several autoantibodies have been investigated and

Competing interests

The authors declare they have no competing interests.

Acknowledgments

This paper is dedicated to the memory of our dear Professor Sergio Chimenti.

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    These authors contributed equally to this paper.

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