LAUSR

Evidence about the influence of microbes in autoimmune diseases such as rheumatoid arthritis (RA) has grown in recent years. However, the precise role of specific bacteria remains largely unknown. Previous investigations identified several oral pathobionts to be specifically targeted by serum antibodies in RA patients.1 In addition, Pianta et al.2 identified recognition of Prevotella copri by the immune system of RA patients. It has to be noted, however, that such findings have neither been reproduced, nor studied in different disease stages. Also, the assumptions made for P. copri relied on a single strain, the type strain DSM18205, isolated from a healthy individual.3 However, there is recent evidence suggesting P. copri to be a non-monotypic species, meaning it clusters into several subspecies displaying geno- and phenotypic differences4.This study aimed to quantify serum antibodies targeting different P. copri strains, as well as known oral pathobionts in patients with different rheumatic diseases or in various stages of RA development.We used custom-made ELISA assays measuring pathogen-specific IgG levels in patient’s serum. Samples were tested against P. copri strains isolated from stool samples of healthy donors and RA patients, as well as the following oral pathobionts: Porphyromonas gingivalis, Prevotella intermedia and Prevotella melaninogenica. We analyzed 120 samples from a Swiss cohort of first-degree relatives, individuals in various pre-clinical RA stages (SCREEN-RA), and 45 samples of patients with established RA (SCQM cohort). These participants were categorized as asymptomatic seronegative individuals (FDR), individuals with ‘systemic autoimmunity associated with RA’ (ACPA and/or RF autoantibodies) (preRA 1), individuals with ’clinically suspect arthralgia’ or ‘undifferentiated arthritis’ with/without autoantibodies (preRA 2) and chronic RA patients (cRA). Additionally, we included 92 serum samples from new-onset patients diagnosed with RA, psoriatic arthritis (PsA) axial spondyloarthritis (SpA), or other non-rheumatic diseases (NRD) recruited via the german RheumaVOR cohort (Table 1).Table 1.Overview human cohort studiescohortSCREEN-RASCQMRheumaVORpatient groupFDRpreRA 1preRA 2cRANRDRAPsAaxSpAtotal numbers4240384532143016age median5454595643.551.550.533sex (F/M)32/1035/534/435/1019/139/515/1510/6ACPA positivity0259310700RF positivity0198340700Overall, there were no significant differences in the IgG reactivity profiles between the patient groups against the distinct P. copri strains or oral pathobionts (Figure 1). However, performing this assay with P. copri strains from distinct subspecies identified clear differences and revealed important variability in the IgG reactivity.Figure 1.Serum IgG responses against different microbes from individuals recruited via SCREEN-RA, SCQM or RheumaVOR cohortOur study failed to reproduce previous results and could confirm neither P. copri nor the three oral pathobionts to be particularly targeted by systemic IgG immune reactions in RA patients. However, we identified strain-specific differences in the IgG reactivity against P. copri, regardless of disease type or state. The latter suggests that the overall immunostimulatory potential of P. copri might be dependent on its strain/subspecies level. Our findings underline the necessity of P. copri strain-level characterization when studying host-microbiota immune interactions.[1]Ogrendik et al. MedGenMed (2005)[2]Pianta et al. Arthritis Rheumatol. (2017)[3]Hayashi et al. Int. J. Syst. Evol. Microbiol. (2007)[4]Tett et al. Cell Host & Microbe (2019)None declared