1995 Fiscal Year Final Research Report Summary
Study on the pathogenesis of Wegener's granulomatosis
| Project/Area Number |
06671700
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Otorhinolaryngology
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| Research Institution | HOKKAIDO UNIVERSITY |
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Principal Investigator |
INUYAMA Yukio Hokkaido University School of Medicine Professor, 医学部, 教授 (70051480)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Wegener's granulomatosis / ANCA / cytokine / adhesion molecule |
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| Research Abstract |
This study examined the role of adhesion molecules in the pathogenesis of Wegener's granulomatosis (WG). For the cytokine, the titers of tumor necrosis factor-alpha (TNF-alpha) are not so high even in the active stage of the disease. The value of soluble ICAM-1 (inter-cellular adhesion molecule-1) in the active stage are significantly high compared with those in the inactive stage of the disease or in healthy volunteers. When we examined the sera of patients individually, the level of soluble ICAM-1 decreases gradually as the disease recover, and the correlation of them was apparently demonstrated. This result means that adhesion of the neutrophils with LFA-1 on its surface take place with the vascular endothelial cells in this disease. However, SLeX or LFA-1, the ligand of the neutrophil, was not revealed to become apparent when activated with TNF-alpha or cANCA (cytoplasmic-antineutrophil cytoplasmic antibody) lgG.It is supposed that integrin such as LFA-1 has two forms, resting form and active form, and its conformational change alter the affinity for the ligand. Further study is needed for this problem.
The study also examined the association between various human leukocyte antigens (HLA) and cANCA-positive WG in Japanese subjects to determine whether HLA antigens are involved in the pathogenesis of this disease. The study involved 16 subjects with cANCA-positive WG treated in our department. HLA-typing of the lymphocytes was performed using a lymphocyte microcytotoxicity assay. Of the subjects with cANCA-positive WG,62.5% (10/16) were positive for HLA-DR9, compared with 26% of the healthy control subjects. This HLA-DR9 elevation was statistically significant (P<0.01, Pc<0.05) ; we also noted a weaker association between HLA-B55 and cANCA-positive WG (P<0.05). The results indicated that an association may exist between certain HLA-class allotypes and WG.
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