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- Title
Two rheumatoid arthritis-specific autoantigens correlate microbial immunity with autoimmune responses in joints.
- Authors
Pianta, Annalisa; Arvikar, Sheila L.; Strle, Klemen; Drouin, Elise E.; Qi Wang; Costello, Catherine E.; Steere, Allen C.; Wang, Qi
- Abstract
In rheumatoid arthritis (RA), immunological triggers at mucosal sites, such as the gut microbiota, may promote autoimmunity that affects joints. Here, we used discovery-based proteomics to detect HLA-DR-presented peptides in synovia or peripheral blood mononuclear cells and identified 2 autoantigens, N-acetylglucosamine-6-sulfatase (GNS) and filamin A (FLNA), as targets of T and B cell responses in 52% and 56% of RA patients, respectively. Both GNS and FLNA were highly expressed in synovia. GNS appeared to be citrullinated, and GNS antibody values correlated with anti-citrullinated protein antibody (ACPA) levels. FLNA did not show the same results. The HLA-DR-presented GNS peptide has marked sequence homology with epitopes from sulfatase proteins of the Prevotella sp. and Parabacteroides sp., whereas the HLA-DR-presented FLNA peptide has homology with epitopes from proteins of the Prevotella sp. and Butyricimonas sp., another gut commensal. Patients with T cell reactivity with each self-peptide also had responses to the corresponding microbial peptides, and the levels were directly correlated. Furthermore, HLA-DR molecules encoded by shared-epitope (SE) alleles were predicted to bind these self- and microbial peptides strongly, and these responses were more common in RA patients with SE alleles. Thus, sequence homology between T cell epitopes of 2 self-proteins and a related order of gut microbes may provide a link between mucosal and joint immunity in patients with RA.
- Subjects
RHEUMATOID arthritis; JOINTS (Anatomy); AUTOANTIGENS; SYNOVIAL fluid; PREVOTELLA; T cells; MICROBIAL peptides; EPITOPES
- Publication
Journal of Clinical Investigation, 2017, Vol 127, Issue 8, p2946
- ISSN
0021-9738
- Publication type
journal article
- DOI
10.1172/JCI93450