Defining the CSF Cytokine and Chemokine Profile of Patients with Autoimmune GFAP Meningoencephalomyelitis

ObjectiveTo describe the cytokine/chemokine profile in the cerebrospinal fluid (CSF) of patients with autoimmune GFAP meningoencephalomyelitis. BackgroundGFAP meningoencephalomyelitis is one of the most common antibody-associated diseases of the central nervous system. The intracellular nature of the antigen suggests a cytotoxic T-cell mediated process, yet the pathophysiology remains poorly understood and patients often have good recovery. Histopathological findings reveal two distinct phenotypes in humans (lymphocytic and granulomatous). Defining the CSF cytokine/chemokine signature in this disease will help elucidate disease mechanisms. Design/MethodsWe utilized a recently validated multiplexed automated immunoassay (Ella by Biotechne) to measure 17 analytes (IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8/CXCL8, IL-10, IL-12p70, IL-13, IL-17A, GM-CSF, TNF-alpha, IFN-gamma, CXCL9, CXCL10, CXCL13, BAFF) in the CSF of GFAP-IgG positive patients tested in a neural antibody clinical service laboratory over a seven-month period. Additionally, CSF of all GFAP-IgG positive patients with clinical data (2016-2024) were evaluated. Results were compared to non-inflammatory disease controls (n=42); comparisons were made with the Wilcoxon rank-sum test. ResultsSeventy-nine patient CSFs were tested so far. IL-5, IL-6, IL-10, IL-8/CXCL8, CXCL9, CXCL10 CXCL13, IFN-gamma, TNF-alpha, GM-CSF and BAFF were significantly elevated in CSF from GFAP patients compared to non-inflammatory controls (P<0.01 for all). Analysis of clinical characteristics of patients, correlations to cytokine elevations, and a comparison to infectious and inflammatory controls are in progress. ConclusionsGFAP meningoencephalomyelitis is associated with significant CSF elevations of cytokines and chemokines associated with T-cell and B-cell responses, as well as macrophage activation; neural cell inflammatory responses might also contribute to these findings. These observations comply with previously reported histopathological findings, but further studies are necessary to identify signatures predicting of outcome and underlying histopathology type.