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International Immunology, Vol. 13, No. 4, 559-565, April 2001
© 2001 Japanese Society for Immunology

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

Masami Takei1, Tetsuyoshi Ishiwata6, Ko Mitamura1, Shigeyoshi Fujiwara2, Katsutoshi Sasaki6, Tatsunari Nishi6, Tetsuro Kuga6, Takahiro Ookubo1,5, Takashi Horie1, Junnosuke Ryu3, Hiroyuki Ohi4 and Shigemasa Sawada1,5

1 First Department of Internal Medicine,
2 Department of Microbiology,
3 Department of Orthopedic Surgery,
4 Second Department of Internal Medicine and
5 Nerima Hikarigaoka Nihon University Hospital, Nihon University School of Medicine, 30-1 Oyaguchi Itabashi, Tokyo 173-8610, Japan
6 Tokyo Research Laboratories, Kyowa Hakko Kogyo Co., Ltd, Machida-shi, Tokyo 194-8533, Japan

Correspondence to: S. Sawada, First Department of Internal Medicine, Nihon University School of Medicine, 30-1 Oyaguchi Itabashi, Tokyo 173-8610, Japan

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

Transmitting editor: K. Okumura


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