phaidra.vetmeduni.ac.at o:4244 DOI 10.1007/s00401-023-02678-7 New insights into neuropathology and pathogenesis of autoimmune glial fibrillary acidic protein meningoencephalomyelitis Anti-glial fibrillary acidic protein (GFAP) meningoencephalomyelitis (autoimmune GFAP astrocytopathy) is a new autoimmune central nervous system (CNS) disease diagnosable by the presence of anti-GFAP autoantibodies in the cerebrospinal fluid and presents as meningoencephalomyelitis in the majority of patients. Only few neuropathological reports are available and little is known about the pathogenic mechanisms. We performed a histopathological study of two autopsies and nine CNS biopsies of patients with anti-GFAP autoantibodies and found predominantly a lymphocytic and in one autopsy case a granulomatous inflammatory phenotype. Inflammatory infiltrates were composed of B and T cells, including tissue-resident memory T cells. Although obvious astrocytic damage was absent in the GFAP-staining, we found cytotoxic T cell-mediated reactions reflected by the presence of CD8+/perforin+/granzyme A/B+ cells, polarized towards astrocytes. MHC-class-I was upregulated in reactive astrocytes of all biopsies and two autopsies but not in healthy controls. Importantly, we observed a prominent immunoreactivity of astrocytes with the complement factor C4d. Finally, we provided insight into an early phase of GFAP autoimmunity in an autopsy of a pug dog encephalitis that was characterized by marked meningoencephalitis with selective astrocytic damage with loss of GFAP and AQP4 in the lesions.Our histopathological findings indicate that a cytotoxic T cell-mediated immune reaction is present in GFAP autoimmunity. Complement C4d deposition on astrocytes could either represent the cause or consequence of astrocytic reactivity. Selective astrocytic damage is prominent in the early phase of GFAP autoimmunity in a canine autopsy case, but mild or absent in subacute and chronic stages in human disease, probably due to the high regeneration potential of astrocytes. The lymphocytic and granulomatous phenotypes might reflect different stages of lesion development or patient-specific modifications of the immune response. Future studies will be necessary to investigate possible implications of pathological subtypes for clinical disease course and therapeutic strategies. eng Humans Animals Dogs Glial Fibrillary Acidic Protein metabolism Encephalomyelitis Pathology Astrocytes Oathology Autoimmune Diseases of the Nervous System Cerebrospinal Fluid Autoimmune Diseases of the Nervous Systemce Therapy Meningoencephalitis Cerebrospinal Fluid Meningoencephalitis Pathology Autoantibodies 2025-07-04T08:43:48.222Z LOMv1.0 Author BEGIN:VCARD VERSION:3.0 N:Yong;Guo; FN:Guo Yong END:VCARD BEGIN:VCARD VERSION:3.0 N:Endmayr;Verena; FN:Verena Endmayr END:VCARD BEGIN:VCARD VERSION:3.0 N:Zekeridou;Anastasia; FN:Anastasia Zekeridou END:VCARD BEGIN:VCARD VERSION:3.0 N:McKeon;Andrew; FN:Andrew McKeon END:VCARD BEGIN:VCARD VERSION:3.0 N:Leypoldt;Frank; FN:Frank Leypoldt END:VCARD BEGIN:VCARD VERSION:3.0 N:Hess;Katharina; FN:Katharina Hess END:VCARD BEGIN:VCARD VERSION:3.0 N:Kalinowska‑Lyszczarz;Alicja; FN:Alicja Kalinowska‑Lyszczarz END:VCARD BEGIN:VCARD VERSION:3.0 N:Klang;Andrea; FN:Andrea Klang X-ORCID:https://orcid.org/0000-0001-5352-5757 END:VCARD BEGIN:VCARD VERSION:3.0 N:Pakozdy;Akos; FN:Akos Pakozdy X-ORCID:https://orcid.org/0000-0001-9816-6970 END:VCARD BEGIN:VCARD VERSION:3.0 N:Höftberger;Elisabeth; FN:Elisabeth Höftberger END:VCARD BEGIN:VCARD VERSION:3.0 N:Hametner;Simon; FN:Simon Hametner END:VCARD BEGIN:VCARD VERSION:3.0 N:Haider;Carmen; FN:Carmen Haider END:VCARD BEGIN:VCARD VERSION:3.0 N:De Simoni;Désirée; FN:Désirée De Simoni END:VCARD BEGIN:VCARD VERSION:3.0 N:Peters;Sönke; FN:Sönke Peters END:VCARD BEGIN:VCARD VERSION:3.0 N:Gelpi;Ellen; FN:Ellen Gelpi END:VCARD BEGIN:VCARD VERSION:3.0 N:Röcken;Christoph; FN:Christoph Röcken END:VCARD BEGIN:VCARD VERSION:3.0 N:Oberndorfer;Stefan; FN:Stefan Oberndorfer END:VCARD BEGIN:VCARD VERSION:3.0 N:Lassmann;Hans; FN:Hans Lassmann END:VCARD BEGIN:VCARD VERSION:3.0 N:Lucchinetti;Claudia F.; FN:Claudia F. Lucchinetti END:VCARD BEGIN:VCARD VERSION:3.0 N:Höftberger;Romana; FN:Romana Höftberger END:VCARD https://w3id.org/kim/hcrt/scheme https://w3id.org/kim/hcrt/text Textdokument Text LOMv1.0 yes https://creativecommons.org/licenses/by/4.0 application/pdf 6995178 https://phaidra.vetmeduni.ac.at/o:4244 https://phaidra.vetmeduni.ac.at/api/object/o:4244/thumbnail LOMv1.0 discipline