Molecular biological study＼ies in a novel peripheral nerve myelin protein and its application to clinical neurology

1999 Fiscal Year Final Research Report Summary

• Project/Area Number: 09670643
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Neurology
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: FURUKAWA Tetsuo Tokyo Medical and Dental University School of Medicine Professor, 医学部, 教授 (80134667)
• Co-Investigator(Kenkyū-buntansha): YAMADA Masahito Tokyo Medical and Dental University Graduate School Associate professor, 大学院・医歯学総合研究科, 助教授 (80191336)
• Project Period (FY): 1997 – 1999
• Keywords: Malignant lymphoma / Peripheral neuropathy / Peripheral nerve myelin / Major myelin protein zero / Monoclonal anti-P0 antibody / Isoform

Research Abstract

We tried to characterize a 35-kd antigen recognized by the serum IgG of a patient with malignant lymphoma and peripheral neuropathy. On western blotting, the serum IgG reacted with a 35-kd antigen in human, bovine and mouse peripheral nerves (PN) but not with other neural and non-neural tissues. Immunohistochemical analysis showed immunoreactivity for the IgG in the compact myelin of PN. We constructed a human sciatic nerve cDNA library and screened it using the patient's IgG. We identified three independent clones. A homology search of the inserts of these clones revealed that the inserts were homologous to P0 cDNA. However, all the inserts corresponded to the 3'-untranslational region of P0 cDNA. Then, to analyze the 35-kd antigen biochmically, myelin fractions of human and bovine sciatic nerve were prepared. Using SDS-polyacrylamide gel electrophresis, the 35-kd antigen was purified from the crude myelin fraction. When the immunoreactivities of the 35-kd antigen for the patient's IgG and monoclonal anti-P0 antibody were compared with those of protein P0 for these antibodies, the 35-kd antigen reacted with both the antibodies, but P0 reacted with only monoclonal anti-P0 antibody. These results indicate the possibility of the 35-kd antigen being an isoform of P0. However, the presence of these autoantibodies against the 35-kd antigen seems to be of little pathological significance, because circulating autoantibodies against the antigen were also found in the sera of patients with malignant lymphoma without associated peripheral neuropathy.