Glial Fibrillary Acidic Protein Immunoglobulin G in CSF

Autoimmunity as a cause of encephalitis is increasingly recognized, fostered by the discovery and clinical validation of diagnostic neural autoantibody biomarkers.¹ Improved recognition of autoimmune encephalitis likely explains its incidence increasing over time to equal or exceed that of infectious encephalitis.² In 2016, an autoimmune disorder targeting the astrocytic intermediate filament protein glial fibrillary acidic protein (GFAP) was described at Mayo Clinic.³ Autoimmune GFAP astrocytopathy is a form of steroid-responsive meningoencephalitis, with or without myelitis, accompanied by elevated CSF white cell count (lymphocyte predominant) and diverse MRI findings in CNS regions that have abundant GFAP, most notably perivascular enhancement radially oriented to the lateral ventricles. In a retrospective series of 101 patients from our institution, we identified that antibodies reactive with the GFAP alpha isoform (GFAPα) in CSF were optimum diagnostic biomarkers.⁴ To ensure high sensitivity and specificity, we and others employ a 2-step diagnostic approach. First, we look for a GFAP-specific pattern of immunoglobulin G (IgG) binding to astrocytic elements by screening on a composite of mouse brain tissues in an indirect immunofluorescence assay format. We then confirm molecular specificity using a GFAPα-transfected cell-based assay.⁴ We have also reported a prospective 1-year experience of 90 patients identified in our laboratory, but drawn from our extramural practice, that revealed similar clinical and radiologic findings among children and adults, but unlike our initial reports, a monophasic course predominated.⁵ A few series (14–22 patients in each) have reported similar findings.^6-8 GFAP-IgG in CSF is the 5th most common autoimmune encephalitis biomarker detected in our laboratory practice (A. McKeon, unpublished observation).