Naturally acquired adaptive immunity to <i>Streptococcus pneumoniae</i> is impaired in rheumatoid arthritis patients.

Evidence Atlas

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

Ercoli, Giuseppe, Selway-Clarke, Hugh, Truijen, Dena et al. · Clinical & translational immunology · 2024 · DOI

Quick Summary

This study compared how well people with rheumatoid arthritis (RA) and ME/CFS patients can fight off a common bacterial infection called Streptococcus pneumoniae. Researchers found that RA patients had weaker immune responses to this bacteria compared to ME/CFS patients, which may explain why RA patients get pneumonia more often. The study also looked at how a common RA treatment (rituximab, which depletes B cells) affected these immune responses.

Why It Matters

This research is important because it provides evidence that RA-associated immunosuppression differs fundamentally from ME/CFS, validating ME/CFS as a useful disease control group. For ME/CFS researchers and patients, this study demonstrates that ME/CFS patients maintain relatively preserved adaptive immune responses to bacterial antigens, which may have implications for understanding infection susceptibility differences between these conditions. Understanding these immune distinctions could inform research into why certain diseases are associated with increased infection risk.

Observed Findings

RA patients showed reduced IgG recognition of approximately 50% fewer S. pneumoniae protein antigens compared to ME/CFS controls.
The median strength of IgG responses to recognized antigens was significantly lower in RA patients.
Reduced antigen-specific IgG responses correlated with reduced IgG opsonisation (bacterial killing ability) of S. pneumoniae.
B-cell depletion therapy with rituximab disrupted pre-existing IgG repertoires to specific antigens in individual RA patients.

Inferred Conclusions

RA is associated with major disruption of naturally acquired adaptive immunity to S. pneumoniae protein antigens.
The protein antigen array is an effective tool for rapidly assessing adaptive immune responses to bacterial pathogens.
Impaired immunity to S. pneumoniae likely contributes to the increased incidence of pneumonia in RA patients.
B-cell depletion therapy has complex effects on pre-existing antibody repertoires despite maintaining overall IgG levels.

Remaining Questions

Does the impaired S. pneumoniae immunity in RA patients improve after RA remission or with different therapeutic approaches?
Which specific aspects of RA pathology—disease activity, duration, medications, or disease-specific mechanisms—most directly cause the observed immune impairment?

What This Study Does Not Prove

This study does not prove that impaired S. pneumoniae immunity directly causes pneumonia in RA patients—only that the association exists. The findings are specific to this bacterial antigen and cannot be generalized to all infections or immune responses. Additionally, the study does not establish whether RA itself or its treatments are primarily responsible for the observed immune impairment, though rituximab's role is partially explored.

Metadata

DOI: 10.1002/cti2.70012
PMID: 39416767
Review status: Editor reviewed
Evidence level: Single-study or moderate support from human research
Last updated: 12 April 2026

About the PEM badge: “PEM required” means post-exertional malaise was an explicit required diagnostic criterion for participant inclusion in this study — not that PEM was studied, observed, or discussed. Studies using criteria that do not require PEM (e.g. Fukuda, Oxford) are tagged “PEM not required”. How the atlas works →