The presence of IgG antibodies in serum or cerebrospinal fluid (CSF) against GFAP, an intermediate filament protein of astrocyte cytoskeletons, is considered the hallmark of Glial Fibrillary Acidic Protein (GFAP) astrocytopathy. This rare autoimmune disorder was introduced in 2016 (1) and consists a novel inflammatory central nervous system disorder. Clinical manifestations include encephalitis, meningoencephalitis and encephalomyelitis. Due to its rarity, comprehensive epidemiological data are not well established.
Recently, however, Ebstein-Barr virus (EBV) infection has been identified as a potential cause of GFAP astrocytopathy induction (2, 3, 4). More specifically, strongly positive anti-GFAP antibodies have been reported in patients with confirmed EBV encephalomyelitis. Fever, headache, cognitive dysfunction, meningeal irritation signs and lower limb weakness comprised the initial symptomatology and MRI was compatible with encephalomyelitis, with characteristic meningeal enhancement, linear enhancement oriented radially to the ventricles and longitudinally extensive lesions in the spinal cord. CSF findings included pleocytosis and elevated protein, detection of EBV DNA and IgG anti-GFAP in both tissue- and cell-based assays. Clinical and radiological improvement/recovery was noted after antiviral therapy and immunotherapy, with no relapses during clinical follow-up.
EBV-related autoimmune CNS reactions have been associated with the virus’s latent and lytic life cycle (2, 3). Concurrent or post-infectious GFAP astrocytopathy should be considered in cases of poor response to antiviral treatment and presence of the above-mentioned characteristic radiological sings (1). Molecular mimicry and EBV involvement in CD8+ T cell-dependent antibody response and B cell activation through the EBV-induced gene 2 (EBI2) (3, 4).
Key Points:
- Positive anti-GFAP antibodies have been reported in patients with EBV encephalomyelitis.
- EBV infection potentially induces GFAP astrocytopathy, through molecular mimicry, CD8+ T cell-dependent antibody response and B cell activation.
- Initial symptoms include fever, headache, cognitive dysfunction, meningeal irritation, lower limb weakness.
- Poor response to antiviral treatment with persistent pleocytosis and MRI findings such as midbrain meningeal enhancement, linear enhancement oriented radially to the ventricles and extensive spinal cord lesions, could guide towards a post-infectious autoimmune syndrome.
References:
- Fang B, McKeon A, Hinson SR, Kryzer TJ, Pittock SJ, Aksamit AJ, Lennon VA. Autoimmune Glial Fibrillary Acidic Protein Astrocytopathy: A Novel Meningoencephalomyelitis. JAMA Neurol. 2016 Nov 1;73(11):1297-1307. doi: 10.1001/jamaneurol.2016.2549. PMID: 27618707.
- Li XL, Wang JY, Li LK, Yang CL, Zhao XL, Yang B, Zhang P, Liu B, Li YB, Zhang ZX, Duan RS. Epstein-Barr virus: To be a trigger of autoimmune glial fibrillary acidic protein astrocytopathy? CNS Neurosci Ther. 2023 Dec;29(12):4139-4146. doi: 10.1111/cns.14336. Epub 2023 Jul 17. PMID: 37458208; PMCID: PMC10651959.
- Zhang JR, Zhuang S, Xu XD, Song WL, Li KR, Jiang Y, Cheng XY, Shi JJ, Hu WD, Liu CF, Zhang YL. Overlapping Epstein-Barr virus encephalitis and autoimmune glial fibrillary acidic protein astrocytopathy. J Neuroimmunol. 2023 Sep 15;382:578174. doi: 10.1016/j.jneuroim.2023.578174. Epub 2023 Aug 7. PMID: 37573633.
- Wang L, Dong L, Zhao M, Jiang C, Geng M, Li S, Xing J, Wang T. A case of EBV encephalomyelitis with positive anti-GFAP-IgG antibody with recurrent fever and dysuresia as the main symptoms: Case report and retrospective analysis. Medicine (Baltimore). 2022 Dec 2;101(48):e31995. doi: 10.1097/MD.0000000000031995. PMID: 36482607; PMCID: PMC9726296.
Publish on behalf of the Scientific Panel on Neuroepidemiology