Naturally acquired adaptive immunity to Streptococcus pneumoniae is impaired in rheumatoid arthritis patients

Abstract

Abstract Purpose: Patients with rheumatoid arthritis (RA) have an increased susceptibility to infection, including those caused by Streptococcus pneumoniae. Why RA is associated with increased susceptibility to S. pneumoniae is poorly understood. This study aims to assess the effects of RA and B cell depletion therapy on naturally acquired antibody responses to 289 S. pneumoniae protein antigens using a novel protein array. Methods: IgG responses to S. pneumoniae were characterized in serum from RA patients and disease controls (myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS)) using whole-cell ELISA, a flow cytometry opsonization assay, and a S. pneumoniae protein array. For the RA patients, results were compared before and after B cell depletion therapy. Results: Compared to a well characterized disease control group of ME/CFS patients, RA patients had reduced antibody responses to multiple S. pneumoniae protein antigens, with significant IgG recognition of approximately half the number of antigens along with reduced median strengths of these responses. Reduction in multiple array antigen-specific responses also correlated with reduced IgG opsonization of S. pneumoniae. Although B cell depletion therapy with rituximab did not reduce overall IgG recognition of S. pneumoniae in the RA group, it was associated with marked disruption of pre-existing IgG repertoire to protein antigens in individual patients. Conclusion: These data show RA is associated with major disruption of naturally acquired adaptive immunity to S. pneumoniae, which can be assessed rapidly using a protein antigen array and is likely to contribute towards the increased incidence of pneumonia in patients with RA.