Heightened Levels of Antimicrobial Response Factors in Patients With Rheumatoid Arthritis

Abstract

Rheumatoid arthritis (RA) is a chronic progressive autoimmune disease leading to considerable disability over time. The disease can be characterized by the presence of multiple autoantibodies in the serum and synovial fluid. Microbial dysbiosis is proposed to play a role in the pathogenesis of RA. Increased systemic bacterial exposure leads to elevated levels of antimicrobial response factors (ARFs) in the circulation. In the present study, we tested whether RA patients have increased levels of ARFs by analyzing the levels of multiple ARFs in serum from RA patients and healthy age and sex-matched controls. The levels of soluble CD14 (sCD14), lysozyme, and CXCL16 were significantly elevated in RA patients compared to healthy controls. Lipopolysaccharide binding protein (LBP) levels remained unchanged in RA patients compared to healthy controls. A positive correlation of LBP with rheumatoid factor (RF) was also found in RA subjects. Interestingly, the levels of anti-endotoxin core antibodies (EndoCAb) IgM, total IgM, EndoCAb IgA, and total IgA were significantly elevated in RA patients compared to healthy controls. No significant changes in the levels of EndoCAb IgG and total IgG were observed in RA patients compared to healthy controls. Furthermore, lysozyme and CXCL16 levels were positively correlated with disease severity among RA subjects. Increases in the levels of several ARFs and their correlations with clinical indices suggest systemic microbial exposure in the RA cohort. Modulation of microbial exposure may play an important role in disease pathogenesis in individuals with RA.

Confirmation and Identification of Biomarkers Implicating Environmental Triggers in the Pathogenesis of Type 1 Diabetes

“…Endotoxin core-specific antibodies (EndoCAbs) provide a sensitive measurement of B cell-driven responses to LPS with elevations and decreases indicating dynamic exposure to endotoxin [reviewed in (19)]. Varying EndoCAb levels have also been associated with autoimmunity (20,21). We found no changes in abundance of EndoCAbs IgA, IgG, and IgM comparing T1D and control (Figures 2A-C).…”

Individuals at risk for rheumatoid arthritis harbor differential intestinal bacteriophage communities with distinct metabolic potential

“…FDR probands were split into cohorts dependent on serum CCP levels, with 100% of subjects in the CCP+ cohort positive and 0% of subjects in either CCP-or HC (Healthy Control) cohorts testing positive. Healthy control subjects were recruited and included in this study as described previously (Ayyappan et al, 2020). The present study consisted of 25 subjects split into 3 cohorts, of which 8 were CCP+, 8 were CCP-, and 9 were HC.…”

Differential effects of periodontal microbiome on the rheumatoid factor induction during rheumatoid arthritis pathogenesis

“…Therefore, LPS was considered as a stimulant of polyclonal antibody formation by B cells, thereby inducing RF production. Another recent study has found the positive correlation between LPS-binding protein and RF, suggesting an important role of systemic microbial exposure in development of RF 31 .…”