Greek rheumatoid arthritis patients have elevated levels of antibodies against antigens from Proteus mirabilis

Abstract

Patients with rheumatoid arthritis (RA) from different ethnic groups present elevated levels of antibodies against Proteus mirabilis. This finding implicates P. mirabilis in the development of RA. The aim of this study was to investigate the importance of P. mirabilis in the etiopathogenesis of RA in Greek RA patients. In this study, 63 patients with RA and 38 healthy controls were included. Class-specific antibodies IgM, IgG, and IgA against three human cross-reactive and non-cross-reactive synthetic peptides from P. mirabilis-hemolysin (HpmB), urease C (UreC), and urease F (UreF)-were performed in all subjects, using the ELISA method. RA patients had elevated levels of IgM, IgG, and IgA antibodies against HpmB and UreC Proteus peptide which are significantly different compared to healthy controls: p = 0.005, p < 0.001, and p = 0.003 and p = 0.007, p = 0.002, and p < 0.001, correspondingly. Also, elevated levels of IgM, IgG, and IgA antibodies against the UreF Proteus peptide-which are non-cross-reactive with human tissue antigens-were observed and their significant difference compared to healthy controls (p = 0.007, p < 0.001, p < 0.001). Anti-peptide antibodies in RA patients showed a significant correlation with rheumatoid factors (Rf), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP), especially when patients were divided into subgroups according to the receiving treatment. Greek RA patients present elevated levels of antibodies against P. mirabilis antigenic epitopes, such as in North European populations, albeit Greek RA patients presenting the cross-reaction antigen in a low percentage. These results indicate that P. mirabilis through the molecular mimicry mechanism leads to inflammation and damage of the joints in RA.

A single bacterium restores the microbiome dysbiosis to protect bones from destruction in a rat model of rheumatoid arthritis

“…To identify the microbial species or strains along with progression and treatment of arthritis, we next conducted a non-negative elastic-net regularized linear regression of the metagenomic sequencing results at the five TPs for each fecal sample against its related arthritis score. In total, 25 microbes were selected, among which Lachnospiraceae bacterium , Proteus mirabilis , and Corynebacterium urealyticum have been found to be related to RA [7, 19]. The relative abundances of the identified 25 microbes were processed by normalization and then presented as log 10 fold changes at each TPs in comparison to TP 1.…”

Detection of human antibodies binding with smooth and rough LPSs from Proteus mirabilis O3 strains S1959, R110, R45

“…It is suggested by us and others that cross-reactivity between bacterial and human antigens is due to molecular mimicry mechanism, that later on may be involved in RA etiopathogenesis (Lorenz et al 2013 ; Christopoulos et al 2017 ; Konieczna et al 2012 ; Rashid and Ebringer 2007 ). Abs against P. mirabilis were recorded at a significantly high level in sera from RA patients which could be due to frequent UTI and asymptomatic bacteuria (Rashid and Ebringer 2007 ).…”

“…Abs against P. mirabilis were recorded at a significantly high level in sera from RA patients which could be due to frequent UTI and asymptomatic bacteuria (Rashid and Ebringer 2007 ). Elevated levels of IgM, IgG and IgA Abs were detected in sera from RA patients reacting with P. mirabilis UreC, UreF, HpmA, HLA-DR1/4 and collagen type XI peptide epitopes (Christopoulos et al 2017 ; Konieczna et al 2012 ; Rashid and Ebringer 2007 ). The presence of anti- P. mirabilis LPSs-Abs in sera from RA patients was not subject of previous studies (Rashid and Ebringer 2007 ).…”

Early and Short-Term Interventions in the Gut Microbiota Affects Lupus Severity, Progression, and Treatment in MRL/lpr Mice

“…Not only that, the antibodies to Klebsiella were positively correlated with anti-dsDNA antibodies in SLE patients (Harkiss et al, 1988). The genus Proteus was not reported to trigger lupus, but it was the main microbial culprit in the causation of rheumatoid arthritis through Proteus peptide (Christopoulos et al, 2017). The early and short-term interventions in the gut microbiota affected not only lupus severity but also lupus progression in MRL/lpr mice.…”