| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2000: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
|---|
| Research Abstract |
In this study, we investigated immune mechanism in the pathogenesis in osteoarthritis (OA) focusing on T cell.
1) Hitological study showed infiltration of CD3 positive T cells into the synovial tissues from OA patients. Clonal infiltration of these T cells was proven by the SSCP analysis, and some of the cells had shared CDR3 region (LEFG, VPTGVG, LRGS) in TCR Vβ chain.
2) Osteopontin (OPN) is one of chondrocyte derived protein. Autoantibody against OPN was detected in 9.5% of sera from OA patients and 15% of rheumatoid arthritis (RA) patients.
3) YKL-39, a cartilage-related protein was expressed as a fusion protein using E-coll system. Autoantibody against human recombinant YKL-39 (hrYKL-39) was detected in 11.1% of sera from OA patients and 11.8% of RA patients. PBL response against hrYKL-39 was studied in the patients whose sera was positive for the protein. PBL reacted with hrYKL-39 in 46% of OA patients, it did in only 17 % of RA patients. From the epitope analysis, one third of the N-terminal fragment had strongest antigenicity.
4) Cartilage intermediate layer protein (CILP), which is secreted in aged cartilage, was expressed as a recombinant protein (hrCILP). Autoantibldy against hrCILP was detected 10.5% of OA patients and 7.9% of RA patients. The strongest antigenicity was revealed in fragment ranging from 422 to 555 amino residue of CILP protein. Moreover, hrCILP induced chronic arthritis in mice.
5) When chondrocytes were co-cultured with self PBL, PBL from OA patients showed higher proliferative response than PBL from RA patients by 5.2 times, This proliferative response was inhibited by anti CD4, CD8, HLA class I and HLA class II antibodies.
In conclusion, autoantibody against some proteins derived from cartilage was detected. There was clonality in T cells infiltrating into synovial tissue in OA.Taken together, T cell mediated immune response might be involved in the pathogenesis of OA.The therapeutic strategy focusing T cells was suggested.
|
