Abstract
Background/Objective: Chronic humoral immune response against multiple microbial antigens may play a crucial role in the etiopathogenesis of rheumatoid arthritis (RA). We aimed to assess the prevalence and magnitude of antibody response against various bacterial and viral immunogen peptides in the sera of RA patients compared with the general population. Methods: Polyclonal IgG antibodies (Abs) specific for peptides derived from Porphyromonas gingivalis (RgpA, Kpg), Aggregatibacter actinomycetemcomitans (LtxA1, LtxA2), Mycobacterium avium subsp. paratuberculosis (MAP4027), Epstein–Barr virus (EBNA1, EBVBOLF), and human endogenous retrovirus (HERV-W env-su) were detected by ELISA in serum samples from 148 consecutive RA patients and 148 sex and age-matched healthy controls (HCs). In addition, the presence of a relationship between the positivity and the titer of antibodies and RA descriptors was explored by bivariate correlation analysis. Results: RA patients exhibit a higher prevalence of humoral immune response against all tested peptides compared to HCs with a statically significant difference for MAP4027 (30.4% vs. 10.1%), BOLF (25.7% vs. 8.1%), RgpA (24.3% vs. 9.4%), HERV W-env (20.3% vs. 9.4%), and EBNA1 (18.9% vs. 9.4%) peptides. Fifty-three (35.8%) out of 148 RA serum and 93 (62.8%) out of 148 HCs were negative for all pathogen-derived peptides. There was a significant correlation between OD values obtained by ELISA test against all peptides (p < 0.0001). We also found an increased titer and prevalence of Abs against LtxA1 and LtxA2 in seropositive vs. seronegative RF (p = 0.019, p = 0.018). Conclusion: This study demonstrates a significantly increased humoral response against multiple pathogens in patients with RA and implies that they could be an important factor in the pathogenesis of the disease. Therefore, the role of each individual pathogen in RA needs to be further investigated.
Highlights
The correlation between OD values obtained by the Enzyme-Linked Immunosorbent Assay (ELISA) test from different peptides, and the rheumatoid arthritis (RA) features, RA activity (DAS-28), systemic inflammation (ESR, C-reactive protein (CRP)), and type of immunosuppressive treatment was explored by bivariate correlation and regression analysis with Stata
We tested the humoral response against selected peptides derived from pathogens previously associated with RA, including P. gingivalis, A. actinomycetemcomitans, Mycobacterium avium subsp. paratuberculosis (MAP), Epstein–Barr virus (EBV), and HERV-W in RA patients in comparison to healthy controls (HCs)
We found that the highest prevalence of humoral response was against MAP, suggesting a contributing role for this microorganism in RA development [8,10]
Summary
The etiology of RA is not well understood Several triggers, such as smoking, infections, and microbiota, have been identified as risk factors for initiating and exacerbating the disease in genetically susceptible individuals [3]. Recent studies have suggested that mucosal surfaces, the periodontium, the gut, and the lungs, might be privileged sites of autoimmunity initiation in RA [5] ignited by a humoral and cytotoxic immune response against mucosal-associated pathogens [6]. Higher prevalence with respect to the general population of the humoral immune response against Mycobacterium avium subsp. This study aimed to evaluate the prevalence and magnitude of the immune response against different highly immunogen microbial peptides derived from P. gingivalis (RgpA, Kpg), A. actinomycetecomitans (LtxA-1, LtxA-2) MAP (MAP_402718–32 ), EBV (EBNA1400–413 , BOLF1305–320 ), and HERV-W env-su. 93–108 in RA patients compared with the general population
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