Antibodies against carbamylated proteins are present in primary Sjögren's syndrome and are associated with disease severity

Abstract

ObjectivesHerein, we investigate the presence and prognostic value of autoantibodies against carbamylated proteins (anti-CarP) in the serum of patients with primary Sjögren's syndrome (pSS).Patients and methodsSerum levels of anti-CarP antibodies were measured in Norwegian patients with pSS (n=78) and corresponding controls (n=74) using ELISA and analysed in relation with exocrine gland function, degree of salivary gland inflammation, signs of ectopic germinal centre (GC) formation and immunological markers. For univariate comparisons, the Mann–Whitney U test and χ2 or Fisher's exact tests were used. Correlations were assessed with Spearman's rank testing. Multivariate regression analyses were used to assess the effect of anti-CarP positivity on clinical manifestations.ResultsOf the patients with pSS, 27% were positive for anti-CarP IgG antibodies. Levels of anti-CarP correlated positively with total IgG, IgM, rheumatoid factor and β2-microglobulin. Importantly, after adjusting for confounding factors, patients positive for anti-CarP had significantly higher focus score. Furthermore, positive anti-CarP status coincided with 9.2-fold higher odds of having developed GC-like structures in the minor salivary glands. As a patient group considered having worse disease outcome, individuals with ectopic GC-like structures also presented with significantly higher levels of anti-CarP antibodies.ConclusionsPresence of anti-CarP in patients with pSS is strongly associated with increased focal lymphocytic infiltration, formation of ectopic GC-like structures in minor salivary glands, and diminished salivary gland function. Even taking into consideration our relatively small cohort we believe that anti-CarP antibodies offer new possibilities for identifying patients with more active disease and at risk of developing additional comorbidity.

The Clinical and Research Implications of Anti-carbamylated Protein Antibodies

“…Anti-CarP was also present in 50% of patients with spondyloarthritis, although only 8 patients were studied in this group. These results build on other recent studies including one by Bergum and colleagues that similarly found an increased prevalence of anti-CarP antibodies in patients with primary Sjögren syndrome 8 .…”

Prevalence, sensitivity and specificity of antibodies against carbamylated proteins in a monocentric cohort of patients with rheumatoid arthritis and other autoimmune rheumatic diseases

“…Beside patients with RA, anti-CarP antibodies were present in a small number of patients with SLE and SS; less than one third of these patients also displayed ACPA positivity. These results can be partially attributed to erosive joint disease described in a small percentage of patients with SLE [21]; besides, carbamylation can be enhanced in patients with kidney involvement or in those with active inflammatory status [8]. Similarly, a clear link between antibody production and the degree of inflammation has been shown in patients with SS, as the activity of circulating myeloperoxidase (MPO), which catalyzes the production of cyanate from thiocyanate, seems to be significantly increased [20].…”

“…Similarly, a clear link between antibody production and the degree of inflammation has been shown in patients with SS, as the activity of circulating myeloperoxidase (MPO), which catalyzes the production of cyanate from thiocyanate, seems to be significantly increased [20]. Two studies investigated anti-CarP in patients with SLE and with SS [20, 21]. The detection of a subset of anti-CarP-positive subjects among patients with SLE or SS and joint involvement suggests the possibility of that anti-CarP might serve as a serological marker for erosive arthritis in AIRDs other than RA.…”

The role for neutrophil extracellular traps in cystic fibrosis autoimmunity

“…In contrast to anti-BPI responses, the lack of association between ACarPa and anti-Cif IgG levels suggests that ACarPA arise independently of infection and are most likely a marker of neutrophil-driven bronchial inflammation reported in other chronic diseases (24,68,69). Alternatively, it may be that ACarPA influence clinical phenotype by impairing the antibacterial activity on NETs.…”