| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1992: ¥200,000 (Direct Cost: ¥200,000)
Fiscal Year 1991: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Research Abstract |
At least one or several genes in human histocompatibility complex (HLA) play roles on the disease process of autoimmune diseases. In Caucasian, it is well established that individuals carrying HLA-DR3,DQ2 are more susceptible to many autoimmune diseases, such as systemic lupus erythematosus (SLE), Sjogren's syndrome (SS), myasthenia gravis (MG), systemic sclerosis (SSc).
In Japanese, however, susceptible gene(s) in the HLA region of diseases listed above are still unclear.
I studied HLA specificities by serological method, restriction fragment length polymorphism (RFLP) of genomic DNA, alleles of class II genes by using polymerase chain reaction-RFLP, and complement 4 (C4) allotypes in 86 patients of SLE, 69 of SS, 74 of MG, 33 of SSc and 36 of polymyositis and/or mixed connective tissue disease (PM/MCTD). The results obtained were as follows.
1) Among SLE patients, individuals positive for HLA-DR4 are more susceptible to lupus nephritis, but resistant to the involvement of central nervou
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s system than those without DR4. The frequency of the null allele of C4A gene (C4AQ0) is higher in SLE patients than in controls, however, deletion of C4A gene was not detected by RFLP method.
2) Higher incidences of HLA-DR53, DPB1*0201 and DQA1*03 were observed in female patients with MG when compared with the controls. The results indicate that Japanese patients with MG can be subdivided into at least two distinct groups. The first group consists of females whose disease onset is early and who have a high frequency of DR53, DPB1*0201 and DQ1*03. The second group consists of males and females with late onset of disease.
No particular HLA allele was found to be associated with the second group. Furthermore at least two distinct HLA class II genes were suggested to play roles on the disease onset of young females with MG.
3) Among SSc, the frequencies of HLA-DR2, C4BQ0 and anti-Scl 70 antibody were higher in patients with pulmonary fibrosis than those without it. Therefore, careful monitoring and treatment at an early stage of disease may necessary in patients the DR2 and C4BQ0. Less
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