Immunopathology of autoantibody-associated encephalitides: clues for pathogenesis

• DOI: 10.1093/brain/aws082
• Publication Date: 2012-04-27T01:05:02Z
• Authors: C. G. Bien; A. Vincent; M. H. Barnett; A. J. Becker; I. Blumcke; F. Graus; K. A. Jellinger; D. E. Reuss; T. Ribalta; J. Schlegel; I. Sutton; H. Lassmann; J. Bauer
• Keywords: Adult; Male; Microscopy, Confocal; Cell Death; Glutamate Decarboxylase; Brain; Electroencephalography; Middle Aged; Magnetic Resonance Imaging; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; ELAV Proteins; Antigens, CD; Antigens, Neoplasm; In Situ Nick-End Labeling; Encephalitis; Humans; Female; Autopsy; Microtubule-Associated Proteins; Aged; Autoantibodies

Classical paraneoplastic encephalitis syndromes with 'onconeural' antibodies directed to intracellular antigens, and the recently described or non-paraneoplastic encephalitides against both neural surface antigens (voltage-gated potassium channel-complexes, N-methyl-d-aspartate receptors) (glutamic acid decarboxylase-65), constitute an increasingly recognized group of immune-mediated brain diseases. Evidence for specific immune mechanisms, however, is scarce. Here, we report qualitative quantitative immunopathology in tissue (biopsy autopsy material) 17 cases either (Hu, Ma2, glutamic decarboxylase) antigenic targets channel-complex receptors). We hypothesized that (intracellular antigen-onconeural antigen-glutamic decarboxylase groups) would show neurodegeneration mediated by T cell cytotoxicity be antibody-mediated less involvement. found a higher CD8/CD3 ratio more frequent appositions granzyme-B(+) cytotoxic cells neurons, associated neuronal loss, (anti-Hu anti-Ma2 cases) compared patients (anti-N-methyl-d-aspartate receptors anti-voltage-gated channel complex cases). One antibody group) showed multiple GrB-positive neurons. Generally, intense inflammation also had relatively low ratios cases. Conversely, complement C9neo deposition on neurons acute death antigen only, specifically voltage-gated patients. receptors-antibody no evidence complement-mediated injury were distinguished from all other absence clear pathology density inflammatory cells. Although samples varied location stage disease, our findings strongly support central role cell-mediated antigens. In encephalitis, subset encephalitides, antibody- response appears responsible loss cerebral atrophy; apparent these mechanisms intriguing requires further study.