Rare variants in genes related to inborn errors of immunity in patients with rheumatoid arthritis and secondary immunodeficiency.
Possibly pathogenic immunity gene variants found in 21.4% of immunodeficient rheumatoid arthritis patients
Rare variants in genes related to inborn errors of immunity in patients with rheumatoid arthritis and secondary immunodeficiency.
Treatment of rheumatoid arthritis (rheumatoid arthritis) relies on immunomodulatory drugs that can compromise immunity, inducing secondary immunodeficiency (secondary immunodeficiency).
With secondary immunodeficiency underwent targeted whole-exome sequencing to identify rare variants in inborn errors of immunity-associated genes.
Among 701 evaluated patients, 70 (10%) had secondary immunodeficiency.
Secondary immunodeficiency was more frequently observed in patients with earlier onset of rheumatoid arthritis, seronegative disease and in those receiving rituximab therapy.
All variants were monoallelic, with 7 of 17 (41.2%) affecting genes involved in canonical NF-κB signalling.
Two patients (3.1%) harboured variants previously reported as pathogenic.
Although rare, underlying inborn errors of immunity can account for immunodeficiency in patients with rheumatoid arthritis.
Identifying patients with inborn errors of immunity among those with rheumatoid arthritis may have important implications for disease management, as it can guide the selection of immunomodulatory therapy and help prevent infectious complications.
Furthermore, it may refine our interpretation of drug safety, particularly in cases of unusual infections that may instead be attributable, rather, to an underlying germline defect.