Identification and characterization of an anti-glial fibrillary acidic protein antibody with a unique specificity in a demented patient with an autoimmune disorder

Abstract

We detected an antibody to a 48 kd antigen of the central nervous system in the serum from a demented patient with an autoimmune disorder. To identify and characterize the antigen, we screened a human cerebral cDNA library and performed immunoblot analysis following two-dimensional gel electrophoresis (2-D blotting). The sequences of the isolated cDNA fragments were homologous to human glial fibrillary acidic protein (GFAP). Two-D blotting using patient serum revealed that the antibody reacted with a restricted subset of GFAP molecules which exhibited relatively high isoelectric points. Furthermore, to elucidate the importance of the anti-GFAP antibody in dementia, we screened for the presence of an anti-GFAP antibody in the sera of 46 demented patients: 26 with Alzheimer's disease and 20 with vascular dementia (VD). We found an anti-GFAP antibody in the serum of only one patient with VD. Two-D blotting revealed that the anti-GFAP antibody in the serum from the VD patient reacted with a more acidic subset of GFAP molecules compared with the anti-GFAP antibody from our patient. In conjunction with the fact that the GFAP molecule with high isoelectric point was insoluble and less degraded, these results suggested that the anti-GFAP antibody in the serum of our patient was not generated due to a secondary response to soluble and degraded GFAP which leaked through the damaged blood–brain barrier as found in the VD patient, but was generated actively on the basis of dysregulation of the immune system. Possible effects of the autoantibody on astrocytic function and the pathogenesis in dementia are discussed.