The investigation of an novel serum autoantibody in patient with chronic inflammatory demyelinating polyneuropathy and paraneoplastic neurological syndeome

Research Project

Project/Area Number	12670594
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Neurology
Research Institution	Kyorin University
Principal Investigator	CHIBA Atsuro Kyorin University, Department of Neurology, Associate Professor, 医学部, 助教授 (30313133)
Co-Investigator(Kenkyū-buntansha)	KUSUNOKI Susumu University of Tokyo, Department of Neurology, Lecturer, 医学部附属病院, 講師 (90195438)
Project Period (FY)	2000 – 2001
Project Status	Completed (Fiscal Year 2001)
Budget Amount *help	¥3,300,000 (Direct Cost: ¥3,300,000) Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000) Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywords	chronic inflammatory demyelinating polyneuropathy / paraneoplastic neurological syndrome / autoantibody / CIDP / anti-nuclear antibody / histone H3 / motor neuron disease / myelin protein / 抗ミエリン蛋白抗体
Research Abstract	Serum autoantibodies were investigated mainly with a Western blot technique using various nervous tissue protein fractions as antigens. During screening with a total protein fraction, extracted from the human sciatic nerve with SDS, the IgM antibody which strongly reacted with a protein of 17.4 kDa was detected in a patient with CIDP. Serum from this patient showed nuclei of Schwann cell stained in IgM class immunohistochemically. The antibody titer did not change before or after IVIg with clinical improvement. Bands of the same mobility on Western blot membranes were also detected in samples from other nervous as well as non-nervous tissues, and protein fraction from the cerebellar cortex showed the strongest reaction with the same amount of total protein. The Further, in an experiment using subcellular fractions prepared from cerebellar tissue, the strongest reaction was detected in the nuclear fraction. The N-terminal amino acid sequencing of the band revealed the antigen was histone H3. However, the patient's serum did not react with histones from bovine thymus, which was available commercially, suggesting that the epitope recognized by the IgM antibody would be portions which was modified postranslationally. Five of 11 patients with CIDP showed antibody titers above the mean +2.5SD (cut-off level) of the healthy controls (n = 20). Moreover, 3 of 10 patient with GBS also showed antibody titers above the cut-off level. When considering antigen localization in the cell and chronological correlation with clinical course, it is unlikely that the detected antibody is directly involved in the pathogenesis of peripheral nerve demyelination in CIDP. However, its significant increase in some patients with CIDP as well as GBS suggests that it may have an association with their immunological or genetical background in these disorders.