Abstract
A large fraction of the patients with rheumatoid arthritis (RA) develop specific autoantibodies, which until recently were only of two types, rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA). We aimed to replicate important findings about a recently described third type of specific autoantibodies, anti-carbamylated protein (anti-CarP) antibodies, because they have been described based only in the homemade ELISA from a single laboratory. Our study included 520 patients with established RA and 278 healthy controls of Spanish ancestry and it was done with an independently performed ELISA. The prevalence and pattern of environmental, clinical and genetic associations of the anti-CarP antibodies were similar to the previously described. Notably, the presence and titers of anti-CarP correlated with the presence and titers of ACPA, but the anti-CarP antibodies did not share the known genetic and exposure risk factors of the ACPA. In addition, anti-CarP antibodies were independently associated with a higher (10.5%) prevalence of bone erosions. The reproducibility of these characteristics across laboratories and European subpopulations, indicates the wide validity of the results and suggests that determination of anti-CarP antibodies could contribute to explain RA pathogenesis and identify clinically relevant patient subgroups.
Highlights
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation in multiple peripheral joints with a symmetric distribution, which untreated will lead to bone erosions, deformities, significant handicap and life shortening [1]
ELISA using carbamylated FCS led to the identification of 29.4% of the RA patients showing this specificity (Fig 1), which is markedly less than the fraction of anti-cyclic citrullinated peptide (CCP) positive patients
We have replicated the following characteristics of anti-CarP antibodies: they were specific of RA, but less sensitive than the anti-CCP antibodies and less correlated with them than rheumatoid factor (RF); in addition, the anti-CarP antibodies were not associated with the RA risk factors, the HLA-DRB1 and PTPN22 risk alleles or with smoking; on the contrary, they were associated with the presence of erosions with independence of the anti-citrullinated protein antibodies (ACPA) status
Summary
Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation in multiple peripheral joints with a symmetric distribution, which untreated will lead to bone erosions, deformities, significant handicap and life shortening [1]. Reproducible Anti-CarP Antibodies in Rheumatoid Arthritis identification of autoantibodies specific of RA has been critical in advancing the understanding of the disease and in the classification of patients with a more uniform clinical pattern. The two well-known autoantibodies are rheumatoid factor (RF), against the Fc of the immunoglobulins, and the anti-citrullinated protein antibodies (ACPA) that are assayed with the anti-cyclic citrullinated peptide (CCP) test. A third type of specific autoantibodies has been described, which show reactivity against carbamylated proteins (anti-CarP) [4]. They could be useful for prediction, diagnosis or follow-up of the patients [4,5,6,7,8,9]
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