Specificity of glial fibrillary acidic protein IgG autoantibody (GFAP-IgG) for Autoimmune Meningoencephalomyelitis Diagnosis (S20.002)

Objective: To describe the disease specificity of GFAP-IgG for autoimmune meningoencephalomyelitis. Background: We recently identified GFAP-specific-IgG as a marker for a spectrum of autoimmune GFAP astrocytopathy. Design/Methods: Three cohorts were evaluated: 1) 38 Mayo Clinic patients (retrospective, 2000–2016); 2) 25 non-Mayo patients (prospective, April–October 2016); and 3) 740 control subjects. GFAP-IgG was detected in serum, CSF or both by indirect immunofluorescence: 1) tissue-based-assay (IFA) utilizing a composite mouse tissue substrate, and 2) cell-based-assay (CBA) for IgG reactive with individual GFAP isoforms (α, ɛ, or κ). Results: All control CSFs were negative by both assays. Rare positivity was encountered in control sera by IFA (0.5%) or CBA (1.5%), but never by both. IgG in all subject patient specimens reacted with GFAPα. Sensitivity and specificity were not enhanced by detecting other isoform reactivities. Among Mayo Clinic patients, the median onset age was 54 years (range, 19–103); 55% were men. Twenty-eight patients (76%) had meningoencephalomyelitis, or limited form. Ten patients (24%) had other syndromes: neuropathy (n=3), ataxia (n=2), brain tumors (n=2), other (n=3). Among the Mayo cohort (n=38), meningoencephalomyelitis specificity of GFAPα-IgG detection in CSF was 95%, but in serum alone was only 10%. With meningoencephalomyelitis diagnosis, MRI accompaniments included hallmark radial, serpentine or ependymal periventricular enhancement (73%) and longitudinally-extensive spinal cord lesions (37%). Improvement with corticosteroid therapy was brisk in 88%, but some patients required additional immunosuppressants to overcome steroid-dependency. Among the non-Mayo cohort (n=25) GFAPα-IgG specificity for meningoencephalomyelitis diagnosis was 100% when detected in CSF (16 patients) and 0% when detected in serum alone (9 patients). Conclusions: Detection of GFAP-IgG in CSF by IFA and confirmation by GFAPα-CBA, is highly specific for autoimmune GFAP meningoencephalomyelitis. Study Supported by: Mayo Clinic Center for Individualized Medicine and Department of Laboratory Medicine and Pathology. Disclosure: Dr. Flanagan has nothing to disclose. Dr. Dubey has nothing to disclose. Dr. Hinson has received (royalty or license fee or contractual rights) payments from Mayo Foundation. Dr. Lennon has received personal compensation from Mayo Foundation-licensed Laboratories. Dr. Fang has nothing to disclose. Dr. Aksamit has nothing to disclose. Dr. Weinshenker has received personal compensation for activities with Novartis, Mitsubishi Pharmaceuticals, Medimmune and Alexion Pharmaceuticals. Dr. Weinshenker has received (royalty or license fee or contractual rights) payments from RSR Ltd., Oxford University and MVZ Labor PD and Mayo Foundation. Dr. Pittock9s institution has received compensation for Dr. Pittock9s activities with Alexion Pharmaceuticals, Medimmune and Chugai Pharma USA. Dr. Pittock and Dr. Pittock9s institution stand to receive patent payments that relate to patents for functional AQP4/NMO-IgG assays and NMO-IgG as a cancer marker. Dr. Pittock has received research support from NIH, Alexion Pharmaceuticals and Medimmune related to autoimmune NMO/AQP4 channelopathy. Dr. McKeon has received research support from MedImmune and Euroimmun.