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

Abstract

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.

Expression of Signaling Lymphocytic Activation Molecule- Associated Protein Interrupts IFN-γ Production in Human Tuberculosis

“…It has been reported that the relative amounts of SAP and SLAM expression may vary during lymphocyte activation and in some autoimmune disorders (25), and that the ratio of SLAM to SAP abundance could have a role in the context-dependent functions of SLAM (9). In fact, the differential expression of SLAM and SAP was proposed to be related to the activation state of the cells (26).…”

Rapid detection of intracellular SH2D1A protein in cytotoxic lymphocytes from patients with X-linked lymphoproliferative disease and their family members

“…It is possible that the expression of SH2D1A protein can be functionally suppressed in these patients, as has been reported in patients with rheumatoid arthritis. 24 Additional studies are needed to determine the relationship between the function of SH2D1A and life-threatening hemophagocytic syndromes.…”

Role of SLAM-Associated Protein in the Pathogenesis of Autoimmune Diseases and Immunological Disorders

“…It was recently reported that SNPs in 2B4 were associated with disease in Japanese rheumatoid arthritis (RA) and SLE patients (Suzuki et al 2008). In addition, the expression of SAP was reduced in peripheral T cells from RA patients (Chan et al 2006;Sawada and Takei 2005;Takei et al 2001), whereas the expression of SLAM was increased in peripheral B cells from these patients (Isomaki et al 1997). Thus the SLAM family-SAP signaling pathway is important for the development of lupus traits and other autoimmune diseases.…”