The pathogenic potential of autoreactive antibodies in rheumatoid arthritis

Abstract

Rheumatoid arthritis (RA) is an autoimmune disease affecting ∼1 % of the population. Although major advances have been made in the treatment of RA, relatively little is known about disease pathogenesis. Autoantibodies, present in approximately 60 % of the patients with early disease, might provide indications for immunological mechanisms underlying RA. Among the RA-associated autoantibodies, especially anti-citrullinated protein antibodies (ACPAs) have been studied intensively in the last decade. The discovery of ACPAs resulted into novel insight in RA pathogenesis and allowed division of the heterogeneous entity of RA into an ACPA-positive and ACPA-negative subset of disease. Other autoantibodies discovered in the serum of RA patients, including rheumatoid factors (RFs) targeting human IgG and anti-peptidylarginine deiminase (PAD)3/4 antibodies reactive against and activating the enzyme involved in citrullination, might contribute in collaboration with ACPAs to a feed-forward loop to aggravate erosive outcome of disease. Recently, a novel autoantibody system associated with RA was identified. These autoantibodies recognize carbamylated proteins (anti-CarP antibodies) and are detected in approximately 20 % of ACPA-negative patients, suggesting another parameter to sub-classify RA. In this review, the implication of autoantibodies in RA pathogenesis, diagnosis, prognosis and as biomarker for personalized medicine is discussed.

Carbamylation of vimentin is inducible by smoking and represents an independent autoantigen in rheumatoid arthritis

“…1 Interestingly, the specific autoimmune response is directed against a number of different antigens modified by post-translational modifications (PTMs). 2 In this context, enzymatic deimination of peptide-bound arginine to citrulline by peptidylarginine deiminases (PADs) is considered as a key mechanism. 3 Studies in different cohorts of RA have revealed that tobacco exposure increases the risk of anti-citrullinated protein/ peptide antibodies (ACPAs) formation, especially in carriers of the shared epitope.…”

Use of Fourier-transform infrared spectroscopy in the diagnosis of rheumatoid arthritis: a pilot study

“…Rheumatoid factor (RFs) and anti-citrullinated peptide antibodies (ACPAs) are the most frequently markers used in disease diagnosis. However, RFs have low specificity [3]. ACPAs are considered as more specific, but repertoire of peptides recognized by ACPAs increase with disease progress.…”

Laboratory diagnostics and pathogenesis of rheumatoid arthritis — the past and the present

“…The focus of researchers is primarily biomarkers useful for assessing disease activity and prognosis of joint damage in patients with RA. Recently, anti-carbamylated (anti-carP) antibodies and calprotectin have been described in RA, which also appears to be promising in the diagnosis of this disease [18][19][20][21][22][23][24][25][26][27][28][29][30].…”

“…However, the relationship between HLA-DRB1 * 03 and positive test for anti-carP in RA patients is considered because, in the anti-carP (+) group, a stronger correlation was observed than in anti-carP (-) patients. In relation to genetic and environmental risk factors, the participation of yet other genes cannot be potentially excluded, which may be important in the development of RA in anti-carP (+) patients [21].…”

“…The so far promising research results indicate that anti-carP antibodies may prove to be a potentially useful biomarker in the diagnostics of RA, in particular in the risk assessment of erosive lesions and progression of lesions visible in radiological examination in RA patients with RA [19][20][21][22][23].…”