Structural Noninfectious Manifestations of the Central Nervous System in Common Variable Immunodeficiency Disorders

Annick van de Ven; Irina Mader; Daniel Wolff; Sigune Goldacker; Hannah Fuhrer; Sebastian Rauer; Bodo Grimbacher; Klaus Warnatz

doi:10.1016/j.jaip.2019.11.039

Structural Noninfectious Manifestations of the Central Nervous System in Common Variable Immunodeficiency Disorders

J Allergy Clin Immunol Pract. 2020 Mar;8(3):1047-1062.e6. doi: 10.1016/j.jaip.2019.11.039. Epub 2019 Dec 16.

Authors

Annick van de Ven¹, Irina Mader², Daniel Wolff³, Sigune Goldacker⁴, Hannah Fuhrer⁵, Sebastian Rauer⁵, Bodo Grimbacher⁶, Klaus Warnatz⁷

Affiliations

¹ Departments of Internal Medicine and Allergology, Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, the Netherlands; Department of Rheumatology and Clinical Immunology, Division of Immunodeficiency, Medical Center of the University Hospital, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
² Department of Radiology, Schön Klinik, Vogtareuth, Germany; Department of Neuroradiology, University Hospital Freiburg, Freiburg, Germany.
³ Department of Internal Medicine III, University Hospital Regensburg, Regensburg, Germany.
⁴ Department of Rheumatology and Clinical Immunology, Division of Immunodeficiency, Medical Center of the University Hospital, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
⁵ Department of Neurology and Neurophysiology, University Hospital Freiburg, Freiburg, Germany.
⁶ Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center, Faculty of Medicine, Albert-Ludwigs-University of Freiburg, Freiburg, Germany; DZIF - German Center for Infection Research, Satellite Center Freiburg, Freiburg, Germany; CIBSS - Centre for Integrative Biological Signalling Studies, Albert-Ludwigs University, Freiburg, Germany; RESIST - Cluster of Excellence 2155 to Hanover Medical School, Satellite Center Freiburg, Freiburg, Germany.
⁷ Department of Rheumatology and Clinical Immunology, Division of Immunodeficiency, Medical Center of the University Hospital, Faculty of Medicine, University of Freiburg, Freiburg, Germany. Electronic address: Klaus.warnatz@uniklinik-freiburg.de.

PMID: 31857261
DOI: 10.1016/j.jaip.2019.11.039

Abstract

Background: Central nervous system (CNS) disease in adult common variable immunodeficiency (CVID) is rare, and therefore diagnostic and therapeutic protocols are lacking.

Objective: To provide clinical information aiming to establish awareness and first experience-based recommendations.

Methods: We reviewed clinical manifestations, genetic and immunological characteristics, diagnostic evaluation, and treatment of patients with CVID with abnormal magnetic resonance imaging (MRI) of the CNS disease in our cohort.

Results: Seventeen patients with CNS manifestation and a previous diagnosis of CVID were identified. Presenting symptoms of the CNS disease included loss of sensory or motoric function, headache, or epilepsy. Contrast-enhancing lesions of the brain or solely the spinal cord were the most common findings on MRI. The prevalence of splenomegaly, lymphadenopathy, interstitial lung disease, and autoimmune cytopenia was significantly increased compared with control CVID patients. In 8 patients, a molecular defect was identified, including mutations in CTLA4, NFKB1, and CECR1. Patients with CVID with CNS involvement generally displayed lymphopenia, skewed CD4⁺ T-cell subsets, and increased proportions of CD21^low B cells in the peripheral blood. CNS involvement usually responded well to high-dose steroids, but regularly required maintenance therapy to prevent relapse.

Conclusion: CNS disease is a severe but rare complication in CVID disorders, particularly affecting patients with other noninfectious disease symptoms. Diagnostic evaluation needs to rule out infectious causes by all means; a genetic evaluation is recommended given the high probability of an underlying monogenic disorder. Possible treatment consists of steroids with yet to be determined optimal maintenance therapy in case of relapse.

Keywords: CVID; Central nervous system; Common variable immunodeficiency; Encephalitis; MRI; Myelitis; Primary immunodeficiency.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
B-Lymphocytes
Central Nervous System
Cohort Studies
Common Variable Immunodeficiency* / diagnosis
Common Variable Immunodeficiency* / genetics
Humans
Mutation