Objective:

To discuss cases of autoimmune neurologic disease with hypogammaglobulinemia independent of immunotherapy.

Background:

Autoimmune neurologic diseases are commonly treated with immune modulating medications, some of which may directly (e.g. PLEX) or indirectly (e.g. B cell-depleting therapies) lead to hypogammaglobulinemia. Hypogammaglobulinemia can be identified during initial laboratory screening or while receiving ongoing immunotherapy for the management of these conditions. Identification of hypogammaglobulinemia may suggest underlying immunodeficiency, warranting additional investigation and treatment to prevent infections while also preventing clinical relapse or disease progression. 

Design/Methods:

This is a retrospective case series of individuals seen at the University of Utah Autoimmune Neurology Clinic who met the following criteria: (1) diagnosis of autoimmune neurologic disease and (2) diagnosis of hypogammaglobulinemia (low IgG, IgA and/or IgM) prior to initiation or long after discontinuation of immunotherapy, or that was disproportionate to immunotherapy.

Results:

Three individuals with 3 distinct autoimmune neurologic diseases and treatment-independent hypogammaglobulinemia were identified: (1) NMDAR encephalitis (NMDARE), (2) MOGAD, and (3) NMOSD. 1/3 individuals had baseline immunoglobulins prior to treatment initiation. All were treated with rituximab during the course of their disease. The individuals with NMDARE and MOGAD were found to have acquired hypogammaglobulinemia during laboratory monitoring following >6 months from last rituximab dose and in the setting of significant infection. The individual with NMOSD was found to have combined variable immunodeficiency in the setting of a VAV1 gene variant, suggesting hereditary immunodeficiency. All experienced long-term control of their autoimmune neurologic conditions without recurrent infections while on IVIG.

Conclusions:

Hypogammaglobulinemia independent of immunotherapy is a rare condition identified in patients diagnosed with autoimmune neurologic diseases. Clinicians should check quantitative immunoglobulins at baseline to minimize etiologic uncertainty, and monitor levels while treating patients with immunotherapy. Assessing for occult hypogammaglobulinemia and immunodeficiency allows physicians to mitigate associated risks that may be exacerbated while on immunotherapy.