Hypogammaglobulinemia: A contributing factor to multiple sclerosis fatigue?

Objective: Fatigue is one of the most disabling and difficult to treat symptoms of autoimmune diseases and frequently presents in people with multiple sclerosis (PwMS). Hypogammaglobulinemia for immunoglobulin G (IgG) affects approximately 8-25% of PwMS. We performed a retrospective analysis to investigate the association of MS-fatigue and IgG hypogammaglobulinemia.
Methods: PwMS, treated at Eginition University Hospital Athens or at the University Hospital Bern, were included (n = 134 patients (Bern n = 99; Athens n = 35)). Mann Whitney U-test (MWT), ANOVA test, Chi ² test and multivariable linear regression models were run.
Results: 97/134 (72.4%) PwMS reported fatigue. In the multivariable linear regression analysis, IgG serum concentration (-1.6, 95%CI -2.7 - -0.5, p = 0.006), daytime sleepiness (0.8, 95%CI 0.2-1.4, p = 0.009), and a depressive mood (1.1, 95%CI 0.8-1.4, p < 0.001) were significantly associated with fatigue. The impact of IgG serum concentration (-2.9 95%CI -4.7 - -1.1, p = 0.002) remained significant also in the subcohort of PwMS without depressive symptoms or daytime sleepiness.
Conclusions: We found an association between IgG hypogammaglobulinemia and fatigue in PwMS (Level of Evidence IV), which might be translated to other autoimmune diseases. It bears a potential therapeutic consequence considering IgG supplementation strategies, if our finding can be validated prospectively.
Competing Interests: Declaration of Competing Interest Diem L received travel grants from Merck, Biogen, Roche and Bayer Schweiz. She also received advisory honoraria or speaker's honoraria from Biogen, Novartis and Merck. All not related to that work. Evangelopoulos ME received travel grants and consulting fees from Biogen, Novartis, Genzyme, Teva, Merck, and Roche. All not related to that work. Karathanassis D has no conflicts of interest. Natsis V has no conflicts of interest. Hammer H received research support and travel grants within the last 5 years from Biogen, Merck, Roche & BMS Friedli C has received travel grants from Biogen, travel grants and advisory honoraria from Sanofi Genzyme, as well as speaker honoraria from Biogen, Novartis and Merck and research support from Chiesi, not related to this work. He reports no conflicts of interest related to this manuscript. Kamber N received travel and/or speaker honoraria and served on advisory boards for Alexion, Biogen, Merck, Sanofi Genzyme and Roche and received research support by Biogen. Salmen A received speaker honoraria and/or travel compensation for activities with Almirall Hermal GmbH, Biogen, Merck, Novartis, Roche, and Sanofi Genzyme and research support by the Swiss MS Society. Chan A has served on advisory boards for, and received funding for travel or speaker honoraria from, Actelion-Janssen, Almirall, Bayer, Biogen, Celgene, Sanofi-Genzyme, Merck, Novartis, Roche, and Teva, all for hospital research funds; and research support from Biogen, Genzyme and UCB. Chan A is associate editor of the European Journal of Neurology and serves on the editorial board for Clinical and Translational Neuroscience and as topic editor for the Journal of International Medical Research. Helbling A has no conflicts of interest. Penner IK has received honoraria for speaking at scientific meetings, serving at scientific advisory boards and consulting activities from Adamas Pharma, Almirall, Bayer Pharma, Biogen, BMS, Celgene, Genzyme, Janssen, Merck, Novartis, Roche, and Teva. She has received research support from the German MS Society, Celgene, Novartis, Roche, and Teva. Walther S received honoraria from Janssen, Lundbeck, Mepha, Neurolite, Otsuka and Sunovion. He served on advisory boards for Lundbeck and Sunovion in 2019. All interests are unrelated to this work. Dr. Walther is associate editor of the European Archives of Psychiatry and Clinical Neuroscience and Frontiers in Psychiatry, in addition, he serves on the editorial board of Neuropsychobiology. Stegmayer K received honoraria from Janssen, Lundbeck, Mepha, and Sunovion. All interests are unrelated to this work. Hoepner R received speaker/advisor honorary from Merck, Novartis, Roche, Biogen, Alexion, Sanofi, Bristol-Myers Squibb, and Almirall. He received research support within the last 5 years from Roche, Merck, Sanofi, Biogen, and Bristol-Myers Squibb. He also received research grants from the Swiss MS Society. All not related to that work.
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