Anti‐modified protein antibodies can be detected in saliva, but not in intestinal secretions of seropositive rheumatoid arthritis patients – evidence of site‐specific mucosal autoantibody secretion in RA

Abstract

ObjectiveAnti‐citrullinated protein antibodies (ACPA) have been detected in sputum and saliva, indicating that anti‐modified protein antibodies (AMPA) can be produced at mucosal sites in rheumatoid arthritis (RA) patients. However, the body's largest mucosal compartment, the gut, has not yet been examined. We therefore investigated the presence of several AMPA (antibodies against citrullinated (ACPA), carbamylated (anti‐CarP) and acetylated (AAPA) proteins) at different mucosal sites, including the intestinal tract.MethodsPaired fecal/ileal wash, saliva and serum samples of RA patients and healthy volunteers were collected in two independent cohorts. Data involving feces was replicated in a third cohort. In these secretions AMPA were analyzed using in‐house ELISA with unmodified peptides as control. In fecal samples total IgA and anti‐E. coli IgA were measured.ResultsACPA, anti‐CarP and AAPA IgA were measurable in saliva of seropositive RA patients (prevalence 9‐40%). No AMPA could be detected in feces. IgA was present since total IgA and anti‐E. coli IgA was detectable in feces of ACPA‐positive RA patients and healthy donors. Results were confirmed in another cohort using colonoscopically collected ileal wash samples.ConclusionOur study shows the presence of ACPA, anti‐CarP and AAPA IgA in saliva of ACPA‐seropositive RA patients. However, no AMPA could be detected in feces/ileal wash samples of these patients, although our assays were able to measure other antigen‐specific antibodies. These data suggest that mucosal autoantibody secretion may occur in the oral mucosa of RA patients, while no evidence could be found for this process in the lower gastro‐intestinal tract.