Background/Purpose:   Antibodies that target carbamylated proteins (anti-CarP) have been implicated in rheumatoid arthritis and are known to associate with joint damage. Furthermore, these autoantibodies can be found years before the onset of RA and the presence of anti-CarP antibodies in arthralgia patients associates with RA development. Although a large amount of clinical data is now available in relation to the occurrence of anti-CarP antibodies, little is known about their characteristics, such as their ability to react against multiple antigens and their capacities to be cross-reactive.

Methods:   We investigated the reactivity of anti-CarP antibodies in serum samples from 160 RA patients (according to the ACR 1987 criteria) and 40 healthy controls using ELISA (enzyme-linked immunosorbent assay).Five different antigens, foetal calf serum, human serum albumin, bovine myelin basic protein, H1 histones and human prothrombin were selected and used in carbamylated and non-modified form. Cross-reactivity within serum samples was investigated using inhibition studies.

Results:   The sera of RA samples are able to recognize a large diversity of carbamylated proteins, with positivity ranging between 39% and 58%. The recognition pattern that is observed is quite diverse, but 24% of the RA patients were able to recognize all 5 carbamylated antigens, while this occurred in none of the control samples. Furthermore, the amount of antigens that can be recognized correlates with the anti-CarP antibody levels. As for cross-reactivity, we observe that antibody binding to one carbamylated protein can often be inhibited by any of the other carbamylated proteins, but not by its non-carbamylated counterpart, indicating the cross-reactive nature of anti-CarP antibodies towards several carbamylated proteins. Interestingly, while anti-CarP antibodies seem to be highly cross-reactive towards different carbamylated antigens, the cross-reactivity towards citrullinated proteins is limited.

Conclusion:  These data suggest that anti-CarP antibodies areable to recognize many different carbamylated proteins. An anti-CarP antibody response initiated by one carbamylated protein may therefore result in recognition of several carbamylated proteins in RA patients. 

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-carbamylated-protein-antibody-cross-reactivity-against-multiple-carbamylated-protein-antigens/