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Neurol Neuroimmunol Neuroinflamm. 2018 Sep 13;5(6):e498. doi: 10.1212/NXI.0000000000000498. eCollection 2018 Nov.

Rituximab-induced hypogammaglobulinemia in patients with neuromyelitis optica spectrum disorders.

Author information

1
Neuroscience Institute Cavalieri Ottolenghi (NICO) (A.M., P.V., S.M., A. Balbo, A. Bertolotto, F.M., G.P.), Orbassano, Turin, Italy; Neurologia-CRESM (A.M., P.V., S.M., A. Balbo, A. Bertolotto, F.M., M.C.), AOU San Luigi Gonzaga, Orbassano, Turin, Italy; "Rita Levi Montalcini" Neuroscience Department (F.M., G.P.), University of Turin, TO, Italy; and Humanitas Hospital Gradenigo (A.D., M.L.), Turin, Italy.

Abstract

Objective:

To evaluate the long-term effects of rituximab (RTX) on total and specific immunoglobulins (Igs) in patients with neuromyelitis optica spectrum disorders (NMOSDs).

Methods:

Total IgG, IgA, and IgM levels were evaluated in 15 patients with NMOSDs treated with RTX (median follow-up 70 months). Anti-aquaporin 4 (AQP4)-IgG titration was performed on samples from 9 positive patients. Anti-tetanus (TET), anti-varicella-zoster virus (VZV), and anti-Epstein-Barr virus nuclear antigen (EBNA) IgGs were also tested in patients with NMOSDs and in 6 healthy controls (HCs).

Results:

RTX reduced total IgG by 0.42 g/L per year, IgA by 0.08 g/L per year, and IgM by 0.07 g/L per year. Hypogammaglobulinemia (hypo-IgG) (IgG < 7 g/L) developed in 11/15 patients. Severe hypo-IgG (IgG < 4 g/L) was found in 3/15 patients, of whom 2 patients developed serious infectious complications. In group analysis, anti-AQP4 IgG titers were reduced by RTX over time, and a significant correlation between anti-AQP4 IgG titers and total IgG levels was found. The effects of RTX were observed on pathogen-specific IgGs as well. In particular, the levels of anti-TET IgG in patients were significantly lower than those in HCs. The half-life of anti-TET IgG was reduced by about 50% in patients compared with the general population.

Conclusions:

Long-term RTX treatment is associated with the risk of hypo-Ig and reduction of anti-TET protection in patients with NMOSDs. Results obtained in this study suggest the importance of monitoring total and specific Ig levels before and during treatment with anti-CD20 drugs to prevent hypo-Ig-related complications and to optimize clinical management.

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