Analysis of TCR Vfi Gene Repertoire in Patients with Rheumatoid Arthritis

Jung, Sung Soo; Hong, Kwan Pyo; Kim, Dong Yook; Kim, Tae Hwan; Lee, In Hong; Jun, Jae Bum; Bae, Sang Cheol; Yoo, Dae Hyun; Kim, Seong Yoon; Lee, Eun Young; Chang, Sung Yeoul; Chai, Young Gyu

Abstract

OBJECTIVES
Polymerase chain reaction (PCR) technology was eamine synovial fluid and peripheral T cells in patients with rheumatoid arthritis(RA) to determine the preferential usage of the T cell receptor(TCR) variable region(V) gene.
METHODS
Oligonucleotide primers specific for individual TCR Vfi gene families were used to amplify the TCR gene products in a semiquantitative assay of their relative utilization in unselected T cell populations.
RESULTS
The result of Vfi utilization was generally heterogenous, similar with previous reports. However, the mean expression of Vfi16 and Vfi18 in RA was more preferentially utilized compared to normal donors. The usage of Vfi in peripheral blood from 3 patients with RA demonstrated restrictions in Vfi16, Vfi 20 and Vfi18 genes, respectively. Analyses of synovial fluid resulted in restriction in Vfi12, Vfi20 and Vfi20, respectively. Although there was no significant pattern of skewed Vfi gene mean usage when comparing the synovial fluids with the peripheral blood T cells from RA patients, there were significant biased Vfi genes, Vfi12, V~I and Vfi20, each 3 patients. As the HLA type is a determining factor in shaping TCR repertoire of peripheral T cells, we compared the Vfi utilization in HLA-DR4 expressing groups that have susceptibility and gene dosage effect in disease progression. It was a little different that comparing the pattern of Vfi usage in peripheral blood and synovial fluid from RA patients between HLA-DR4 positive and negative group.
CONCLUSION
The results were consistent with the conclusion that the increased Vfi family T cells infiltrate synovium and are dependent on each patient and may be involved in inducing and maintaining the synovitis that characterizes RA. The different outcome of each patient may be due to the difference in disease duration, genetic background and geographic region. A more important factor may be the stage of disease, because epitope 'induced immune reaction may change over time. Therefore, selecting patients early in the course of disease may be important and may facilitate the need for more in-depth TCR analysis in the future.