Immune responses to gut bacteria may be tied to inflammation in RA

Last Updated: 2017-07-03

By David Douglas

NEW YORK (Reuters Health) - Proteins derived from gut bacteria prompt immune responses in synovial tissue from patients with rheumatoid arthritis (RA), according to Boston-based researchers.

The finding suggests "a potential link between autoimmune responses and microbial immune reactivity," Dr. Annalisa Pianta told Reuters Health by email.

As reported June 26 online in The Journal of Clinical Investigation, Dr. Pianta of Massachusetts General Hospital and colleagues studied patients with RA, patients with other rheumatic diseases and healthy controls.

The researchers found N-acetyl-glucosamine-6-sulfatase (GNS) and filamin A (FLNA) antigens in the synovial fluid and RA-affected joints, which they say show remarkable similarity to those produced by common classes of intestinal bacteria.

"The HLA-DR-presented epitopes from GNS and FLNA have considerable sequence homology with Prevotella epitopes and with similar epitopes from several related gut commensals," Dr. Pianta said.

GNS and FLNA exposure prompted T cell responses in 52% of tested RA patients and B cell responses in 56%. There was no response in patients with other rheumatic diseases or healthy controls.

Patients with T cell reactivity to each self-peptide, say the investigators, "also had responses to the corresponding microbial peptides, and the levels were directly correlated." This suggests that "that T cell epitope mimicry may provide a potential link between mucosal immunity and immune responses in affected joints."

The findings have diagnostic implications, according to Dr. Pianta.

"The addition of GNS and FLNA to standard autoantibody determinations (anti–citrullinated protein antibody (ACPA) and rheumatoid factor) increased the percentage of seropositive patients from 69% to 86% improving diagnostic support for patients with seronegative RA," she said.

"In addition," she pointed out, "the inclusion of citrullinated GNS in a test for ACPA may increase the sensitivity of that testing."

Dr. Pianta concluded, "These are the first observations providing a potential link between mucosal immunity and autoimmune responses to these highly expressed proteins in the joints of RA patients. Therefore, targeted antibiotic regimens or diet alterations may have an adjunctive role to DMARD treatment in patients showing immune responses to gut microbes."

SOURCE: http://bit.ly/2sjin5S

J Clin Invest 2017.