Detection of anti-SARS-CoV-2 antibodies in patients with rheumatoid arthritis.

Objectives: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) and the outbreak of COVID-19 was reported in December 2019 in Wuhan, China. Serological test is conducted to discriminate prior infection of SARS-CoV-2. The influence of auto-antibodies on the results of anti-SARS-CoV-2 antibodies was investigated in a few studies. Here, we investigated whether the results of anti-SARS-CoV-2 antibodies would be modified in patients with rheumatoid arthritis (RA). Methods: Patients with RA were recruited at Sagamihara National Hospital from July 2014 to October 2015 (n=38, 2014 cohort) and at Tokyo National Hospital from June to October 2020 (n=93, 2020 cohort). Anti-SARS-CoV-2 antibodies were measured in collected sera from these RA patients by electrochemiluminescence immunoassay (ECLIA) or immunochromatographic assay (ICA). Results: Anti-SARS-CoV-2 antibodies were not detected in all the samples form RA patients in both cohorts by the ECLIA. However, anti-SARS-CoV-2 antibodies were detected in the serum samples from three (7.9%) in 2014 cohort by the ICA and fifteen (16.1%) in 2020 cohort. The IgM rheumatoid factor levels were increased in RA patients with IgM anti-SARS-CoV-2 antibodies by ICA compared with RA without any anti-SARS-CoV-2 antibodies (mean ± standard deviation [IU/ml], 1223.0 ± 1308.7 vs. 503.6 ± 1947.2, P=0.0101). The levels of IgG rheumatoid factor were also upregulated in RA patients with IgM anti-SARS-CoV-2 antibodies by ICA (4.0 ± 0.7 vs. 2.4 ± 0.9, P=0.0013). Conclusion: The results of IgM anti-SARS-CoV-2 antibody by the ICA would be modified by IgM or IgG rheumatoid factors in RA patients.

Role of PIR-B in Autoimmune Glomerulonephritis

PIR-B, an inhibitory receptor expressed on murine B cells and myeloid cells, regulates humoral and cellular immune responses via its constitutive binding to the ligand, MHC class I molecules, on the same cells (cis) or on different cells (trans). Although it has been speculated that PIR-B is important for maintaining peripheral tolerance, PIR-B single deficiency does not cause overt autoimmune diseases. Recently, however, the combination of its deficiency with the Faslprmutation was found to result in augmented production of autoantibodies such as IgG rheumatoid factor and anti-DNA IgG, leading to glomerulonephritis in mice. Although the precise molecular mechanism for the overall scenario is unclear, PIR-B was found to suppress TLR9-mediated production of naturally autoreactive antibodies by innate B cells or B-1 cells by inhibiting the activation of Bruton's tyrosine kinase. Thus, PIR-B is an important regulator of innate immunity mediated by TLR9 in B-1 cells, which can otherwise provoke autoimmunity when overactivated.