“In our study, RA patients had either IgG or IgA antibody responses, but rarely both. Patients with P copri antibodies usually had ACPAs [anti-citrullinated protein antibodies], whereas patients with P copri IgG antibodies less frequently had such autoantibodies.
“This suggests that ACPA responses may help initially to control the containment of commensals in the gut, whereas patients lacking ACPA responses may have spread of P copri beyond the gut, accompanied by microbial IgG responses and evidence of P copri DNA in joints,” Dr. Pianta says. The antibody levels to B fragilis and E coli were similar or lower in patients with RA than in patients with other arthritides or in the healthy control group. Also, there was little overlap between patients with P gingivalis antibodies and those with P copri antibodies, she says.
The P copri antibody responses were primarily found in women in this study. In a comparison between the cohorts of new-onset and chronic RA who did or did not have IgG or IgA antibody responses to the microbes, 45 of the 50 patients with P copri antibody responses were female compared with 60 of the 86 patients who lacked those responses.
When information from the two cohorts was combined, P copri-negative patients had a sex ratio of 2.3 to 1 in favor of women, close to the ratio of 3 to 1 that is commonly reported in RA cohorts, according to the investigators. The patients with P copri antibody responses had a female sex ratio of 9:1, which implies the organism may substantially contribute to the female predominance in RA, they said.
“Why the antibody responses were found primarily in women is not yet clear,” Dr. Pianta says. “One possibility is that the gut microbiota may differ between men and women. Additional studies will be needed to clarify this specific aspect.”
Implications for Diagnosis, Treatment
According to Dr. Pianta, research indicates that testing for IgG antibody responses to P copri may help identify patients “who are negative for ACPA and/or rheumatoid factor (RF), thereby supporting the diagnosis in seronegative RA patients. This may help in earlier DMARD [disease-modifying anti-rheumatic drug] treatment for this group of patients.”
The research findings suggest that bowel pathology may be a feature of the disease in a subgroup of patients. P copri “may spread from the bowel in repeated waves over a period of years, perhaps explaining the persistence of antibody responses to P copri in patients with chronic RA,” the investigators say.
