Is There an Interactive Effect of Immunoglobulin Levels and CD4+ Cell Counts During Rituximab Treatment? Comment on the Article by Mélet et al


I was pleased to read the recent article by Mélet et al on lymphocyte/CD4+ cell depletion induced by rituximab and its role in determining treatment response in rheumatoid arthritis (RA) patients at 6 months ([1]). I wondered whether the authors considered the interactions between immunoglobulin levels and lymphocyte/CD4+ cell counts after rituximab treatment, in relation to response and infection.

Previous studies have shown that low lymphocyte counts at baseline seem to predict good response in seropositive RA patients treated with rituximab ([2]), whereas high levels of total Ig (>12 gm/liter) at baseline ([3]) and high levels of IgA (>4 gm/liter) at 5 months ([4]) were predictive of poor response in RA. After multiple courses of rituximab, RA patients with low baseline Ig levels tended to develop persistent hypogammaglobulinemia, and relapses tended to be more independent of B cell repopulation in patients with low IgM levels ([5]). It is unknown whether CD4+ cell counts were higher among these RA patients with low IgM levels and relapsing disease.

Mélet and colleagues showed that early rituximab re-treatment (at 6–12 months) led to greater CD4+ cell depletion ([1]). My colleagues and I have observed that after multiple courses of rituximab re-treatment in patients with granulomatosis with polyangiitis (Wegener's) (GPA), those who developed lower immunoglobulin levels and lower CD4+ cell counts were at increased risk of infection ([6]). Thus, allowing B cell repopulation and higher CD4+ cell counts before initiating rituximab re-treatment could reduce the risk of infection both in GPA patients and in susceptible RA patients.