Rituximab-induced hypogammaglobulinemia in autoimmune cytopenia and associated diseases

Rituximab is used for treating autoimmune cytopenia and associated diseases including autoimmune haemolytic anaemia; immune thrombopenia, systemic lupus erythematosus and antiphospholipid syndrome. However, rituximab may induce acquired immune deficiency in some patients, particularly hypogammaglobulinemia (HG), whose risk factors remain poorly defined.

We conducted a retrospective multicentre study including patients with autoimmune cytopenia and related diseases who received at least one rituximab infusion to validate serum protein electrophoresis (SE) as a screening tool for HG and to assess its incidence, risk factors, and clinical outcomes. Univariate and multivariate Cox analysis were performed to characterize predictor of HG.

Among 47 patients (391.89 person-years follow-up), Gammaglobulin evaluation on SE strongly correlated with IgG (ρ = 0.97, P=2.2×10^-16). HG, defined as gammaglobulin levels <7g/L on SE after rituximab exposure, occurred in 14.9% of patients and was associated with a higher cumulative number of rituximab injections (median 11 vs. 1.5; P=0.033). All immunoglobulin isotypes declined after treatment, and severe infections were more frequent in HG patients. Although cumulative rituximab dose and corticosteroid exposure were associated with HG in univariate analysis, these findings were not confirmed in multivariate models.

SE appears to be a reliable screening tool for HG, but larger studies are needed to clarify risk factors.