Age, low immunoglobulin G, and M serum levels predict infections in people with AQP4-IgG+ NMOSD treated with rituximab-A multicenter cohort study from the German Neuromyelitis Optica Study Group (NEMOS)

Engels, Daniel; Herfurth, Mariella; Havla, Joachim; Schindler, Patrick; Ruprecht, Klemens; Schwake, Carolin; Ringelstein, Marius; Fischer, Katinka; Schubert, Charlotte; Schiffmann, Insa; Hümmert, Martin W; Giglhuber, Katrin; Jarius, Sven; Vardakas, Ioannis; Grothe, Matthias; Etgen, Thorleif; Warnke, Clemens; Naumann, Jasmin; Hoffmann, Frank; Senel, Makbule; Wildemann, Brigitte; Berthele, Achim; Trebst, Corinna; Häußler, Vivien; Aktas, Orhan; Ayzenberg, Ilya; Bellmann-Strobl, Judith; Bergh, Florian Then; Kümpfel, Tania

Age, low immunoglobulin G, and M serum levels predict infections in people with AQP4-IgG+ NMOSD treated with rituximab-A multicenter cohort study from the German Neuromyelitis Optica Study Group (NEMOS)

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Item Type:	Article
Title:	Age, low immunoglobulin G, and M serum levels predict infections in people with AQP4-IgG+ NMOSD treated with rituximab-A multicenter cohort study from the German Neuromyelitis Optica Study Group (NEMOS)
Creators Name:	Engels, Daniel, Herfurth, Mariella, Havla, Joachim, Schindler, Patrick, Ruprecht, Klemens, Schwake, Carolin, Ringelstein, Marius, Fischer, Katinka, Schubert, Charlotte, Schiffmann, Insa, Hümmert, Martin W, Giglhuber, Katrin, Jarius, Sven, Vardakas, Ioannis, Grothe, Matthias, Etgen, Thorleif, Warnke, Clemens, Naumann, Jasmin, Hoffmann, Frank, Senel, Makbule, Wildemann, Brigitte, Berthele, Achim, Trebst, Corinna, Häußler, Vivien, Aktas, Orhan, Ayzenberg, Ilya, Bellmann-Strobl, Judith, Bergh, Florian Then and Kümpfel, Tania
Abstract:	INTRODUCTION: Rituximab is effective and widely used as long-term treatment in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4-IgG+ NMOSD). However, infections remain a significant concern during rituximab treatment. METHODS: We conducted a retrospective multicenter cohort study within the NMO Study Group (NEMOS) in Germany, analyzing demographic and clinical data from people with AQP4-IgG+ NMOSD receiving rituximab or azathioprine by retrospective chart, and compared infection occurrence and severity. For rituximab-treated patients, we collected laboratory data (blood lymphocytes, B-cell counts, serum IgG, IgM, and IgA levels), assessed risk factors for infections, and determined the probability of infection within a 3-month window before and after the laboratory assessment. RESULTS: In 92/170 rituximab and in 12/33 azathioprine treatment episodes, one or more infections were documented. Rituximab and azathioprine showed comparable types and risk of infection (HR = 1.24, 95% CI: 0.68-2.25). Rituximab-treated individuals older than 60 years had a higher risk of infection (HR = 1.62, 95% CI: 1.02-2.57). Hypogammaglobulinemia (IgG < 6.0 g/L: OR = 2.27, 95% CI: 1.15-4.48; IgM < 0.3 g/L: OR = 2.08, 95% CI: 1.05-4.09) predicted infections and the occurrence of both low IgG and IgM serum levels further increased the risk of infection (OR = 2.77, 95% CI: 1.10-6.98) during rituximab treatment. Low IgG and IgA serum levels as well as lymphopenia predicted infection-related hospitalizations. CONCLUSION: Age > 60 years and immunoglobulin serum levels during rituximab treatment may serve as predictors for infection and help to individualize treatment decisions in NMOSD.
Keywords:	AQP4-IgG, Hypogammaglobulinemia, Infections, NMOSD, Rituximab
Source:	European Journal of Neurology
ISSN:	1351-5101
Publisher:	Wiley
Volume:	33
Number:	2
Page Range:	e70520
Date:	February 2026
Official Publication:	https://doi.org/10.1111/ene.70520
PubMed:	View item in PubMed

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