Human monoclonal antineurofilament antibody cross-reacts with a neuronal surface protein.
Increased titres of anti-neurofilament antibodies have been reported in neurodegenerative disorders, and it has been suggested that such antibodies might be pathogenic. We investigated the specificity of an IgA monoclonal antibody (MAb) from a patient with amyotrophic lateral sclerosis which reacted with neurofilaments and bound to the surface of neuroblastoma cells. In Western blots, the immunoaffinity-purified IgA bound to the 220-kD, high-molecular-weight neurofilament protein (NFH) and cross-reacted with several closely migrating protein bands with apparent mobility of 62-68 kD in neuroblastoma cells and extracts of normal human spinal cord. Following crosslinking to the surface of radiolabeled neuroblastoma cells, the IgA MAb immunoprecipitated a 65-kD protein, indicating that the protein was present on the cell surface and available to the antibodies for binding. Several other MAbs to NFH did not immunostain the surface of neuroblastoma cells or bind to the 65-kD protein, indicating that the protein was not a fragment of NFH. Thus, antibody binding to the 65-kD protein, possibly by cross-reacting with NFH, may have contributed to the neuronal degeneration.
Sadiq
S A
SA
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, New York 10032.
van den Berg
L H
LH
Thomas
F P
FP
Kilidireas
K
K
Hays
A P
AP
Latov
N
N
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000032:analysis; D003429:Cross Reactions; D006801:Humans; D007070:Immunoglobulin A; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000276:immunology*; D009447:Neuroblastoma / Q000737:chemistry; D016900:Neurofilament Proteins / Q000276:immunology*; D009474:Neurons / Q000166:cytology*; D010525:Peripheral Nerves / Q000737:chemistry*; D013116:Spinal Cord / Q000737:chemistry*; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D007070:Immunoglobulin A; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins