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.

We used a new tactile sensor to measure the elastic properties of skin in patients with systemic sclerosis or Raynaud's phenomenon. The sensor consists of a piezoelectric vibrator with vibration pickup to measure frequency changes when the sensor is placed on the skin. The mean frequency change at the skin surface of the proximal third phalanx in patients with systemic sclerosis was significantly lower than in age-and sexmatched controls. The results in systemic sclerosis patients were statistically correlated to the Modified Rodnan Skin Thickness Score. This technique was also used to measure the therapeutic efficacy of salpogrelate, a new specific serotonin receptor antagonist. A greater mean frequency change was seen after treatment. We conclude that this new tactile sensor is useful for quantitatively measuring skin sclerosis and may help determine the efficacy of therapeutic treatments.

Anti-nucleosome antibodies, which recognise conformational epitopes consisting of histone and DNA in chromatin, have been described in autoimmune diseases. In this study, an attempt was made to isolate anti-nucleosome antibodies from the anti-DNA-depleted plasma IgG of two lupus patients either with or without nephritis by nucleohistone affinity chromatography. The purified nucleohistone-binding antibodies bound to nucleohistone in a specific manner and contained enriched anti-histone antibodies. However, adsorption of the purified antibodies with histone revealed that the nephritis patient-derived antibodies contained nucleohistone-specific antibodies. Although such purified antibodies may not recognise native structures of nucleosomes, this chromatography may provide a method to isolate and determine the fine specificity of anti-nucleosome antibodies in various autoimmune diseases.

SUMMARYThe effect of fibronectin on IL-1a, IL-1j3, tumour necrosis factor-alpha (TNF-a), and IL-6 production was investigated with cultured monocytes isolated from human peripheral blood. Monokine concentrations were determined by both ELISA and bioassay. Fibronectin markedly stimulated the secretion of IL-1 a, IL-1,6, TNF-a and IL-6 from cultured monocytes in a dosedependent manner, with the maximal effect apparent within 24 h. Northern blot analysis revealed a marked increase in the abundance ofmRNA specific for each monokine on exposure ofmonocytes to fibronectin. Monoclonal antibodies to the a chain of very late antigen (VLA)-5, the,61 integrin, the a chain of Mac-I, and the ,62 integrin, as well as the synthetic peptide of GRGDSP (which corresponds to the cell-binding domain of fibronectin), inhibited (>50%) fibronectin-induced monokine production. Monoclonal antibodies to the a chain ofVLA-4, and the a chain of LFA-I, as well as the synthetic peptide CS-I (which corresponds to the alternatively spliced connecting segment of fibronectin) and the control peptide GRADSP, had no inhibitory effect on monokine production. A MoAb, R60, that recognizes an epitope of the fibronectin molecule that includes the RGD sequence, inhibited monokine production, whereas the MoAb Y16, which recognizes another epitope of fibronectin not including RGD, did not. These results indicate that fibronectin-induced production of IL-Ia, IL-1,6, TNF-a and IL-6 from cultured monocytes is mediated predominantly by interaction of the cell-binding domain of fibronectin with VLA-5, although Mac-1 also may contribute to this effect of fibronectin. Our results indicate that the interaction of fibronectin with integrins may contribute to the cytokine network in inflammatory response.