Humoral Response to Microbial Biomarkers in Rheumatoid Arthritis Patients

Seyedesomaye Jasemi; Gian Luca Erre; Maria Luisa Cadoni; Marco Bo; Leonardo A Sechi

doi:10.3390/jcm10215153

Humoral Response to Microbial Biomarkers in Rheumatoid Arthritis Patients

J Clin Med. 2021 Nov 2;10(21):5153. doi: 10.3390/jcm10215153.

Authors

Seyedesomaye Jasemi¹, Gian Luca Erre^{2

3}, Maria Luisa Cadoni^{2

3}, Marco Bo¹, Leonardo A Sechi^{1

4}

Affiliations

¹ Department of Biomedical Sciences, University of Sassari, Viale San Pietro 43b, 07100 Sassari, Italy.
² Department of Medical, Surgical and Experimental Sciences, University of Sassari, 07100 Sassari, Italy.
³ Dipartimento di Specialità Mediche, Azienda Ospedaliero Universitaria di Sassari, 07100 Sassari, Italy.
⁴ Struttura Complessa di Microbiologia e Virologia, Azienda Ospedaliera Universitaria di Sassari, 07100 Sassari, Italy.

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.

Keywords: A. actinomycetemcomitans; Epstein–Barr virus; M. avium subspecies paratuberculosis; P. gingivalis; human endogenous retroviruses; immune response; rheumatoid arthritis.