Journal Article

Decreased expression of signaling lymphocytic-activation molecule-associated protein (SAP) transcripts in T cells from patients with rheumatoid arthritis

Masami Takei, Tetsuyoshi Ishiwata, Ko Mitamura, Shigeyoshi Fujiwara, Katsutoshi Sasaki, Tatsunari Nishi, Tetsuro Kuga, Takahiro Ookubo, Takashi Horie, Junnosuke Ryu, Hiroyuki Ohi and Shigemasa Sawada

in International Immunology

Published on behalf of Japanese Society for Immunology

Volume 13, issue 4, pages 559-565
Published in print April 2001 | ISSN: 0953-8178
Published online April 2001 | e-ISSN: 1460-2377 | DOI: http://dx.doi.org/10.1093/intimm/13.4.559
Decreased expression of signaling lymphocytic-activation molecule-associated protein (SAP) transcripts in T cells from patients with rheumatoid arthritis

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The function of Epstein–Barr virus (EBV)-specific cytotoxic T cells is disturbed in rheumatoid arthritis (RA) patients but the mechanism for this disturbance has remained unknown. In a recent study searching for the causative gene of X-linked lymphoproliferative syndrome, the gene possibly linked to EBV-specific cytotoxic T cells or NK cell-mediated cytotoxic activity to EBV-infected cells was discovered, and its product is now referred to as signaling lymphocytic-activation molecule-associated protein (SAP) or Src homology 2 domain-containing protein (SH2D1A). In the present study, we attempted to investigate the involvement of the SAP gene in RA using a quantitative real-time PCR; the expression level of SAP transcripts in peripheral leukocytes or T cells was examined for patients with RA. The expression level of SAP transcripts in peripheral leukocytes of 21 RA patients was significantly lower than that of 13 normal individuals (P = 0.0007), four patients with palindromic RA, 11 with inactive systemic lupus erythematosus (SLE) or 17 with chronic renal diseases. The decreased expression of SAP transcripts in RA patients was also observed in peripheral CD2+ T cells compared with normal individuals. There was no mutation in the coding region of SAP cDNAs derived from peripheral leukocytes of five RA patients. The decreased expression of SAP transcripts in peripheral leukocytes or T cells of RA patients might lead to the failure of the immune system to eliminate the EBV-infected synovial lining cells in joints of RA patients. Our findings have suggested that decreased expression of the SAP gene might be involved in the onset or progress of RA.

Keywords: molecular biology; mRNA; rheumatoid arthritis; T lymphocyte; EBER Epstein–Barr virus-encoded small RNA; EBV Epstein–Barr virus; LMP latent membrane protein; OA osteoarthritis; RA rheumatoid arthritis; RANA RA-associated nuclear antigen; SAP SLAM-associated protein; SHP-2 Src homology 2-domain-containing protein tyrosine phosphatase-2; SLAM signaling lymphocytic-activation molecule; SLE systemic lupus erythematosus; XLP X-linked lymphoproliferative syndrome

Journal Article.  5291 words.  Illustrated.

Subjects: Immunology ; Biological Sciences

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