Autoantibodies to small nuclear and cytoplasmic ribonucleoproteins in japanese patients with inflammatory muscle disease

Abstract

Objective. To elucidate the profile and clinical significance of autoantibodies to small nuclear and small cytoplasmic ribonucleoproteins in Japanese patients with polymyositis and dermatomyositis (PMBM).Methods. Radioimmunoprecipitation assays were performed with sera from 91 patients with various inflammatory muscle diseases and from 254 control patients with other rheumatic diseases. Patients with PWDM were categorized according to autoantibody specificities, and clinical comparisons were made.Results. Antibodies to aminoacyl transfer RNA (tRNA) synthetases and the signal recognition particle (SRP) were found to be specific for PM/DM. PWDM

Histidyl-tRNA Synthetase

“…Antibodies against an antigen called Jo-1 were found in 20 -30% of the sera of myositis patients (Mathews and Bernstein, 1983;Dang et al, 1985Targoff et al, 1988;Targoff and Arnett, 1990;Marguerie et al, 1990;Goldstein et al, 1990;Tsui and Siminovitch, 1991;Shi et al, 1991;Lopez et al, 1991;Targoff, 1991Targoff, , 1993Hirakata et al, 1992;Treher et al, 1993;Garlepp, 1993;O'Neill and Maddison, 1993;Mitra et al, 1994;O'Hanlon et al, 1994;Chmiel et al, 1995;Fischer et al, 1995;Gelpi et al, 1996;Vazquez-Abad and Rothfield, 1996a;Friedman et al, 1996;Rutjes et al, 1997;Kalenian and Zweiman, 1997;Miller et al, 1998). Immunoblot assays (Williams et al, 1986;Fonong et al, 1990) and ELISA tests were developed (Biswas et al, 1987b;Targoff and Reichlin, 1987) for detection of anti-Jo-1, which does not seem to correlate with cellular muscle damage (Suzuki et al, 1993).…”

“…Noncompetitive inhibition was observed with respect to tRNA His , indicating that the antibodies bind to free and tRNA His -bound HisRS. Autoantibodies from patients with polymyositis and dermatomyositis react with ribonucleoproteins (Hirakata et al, 1992). Anti-Jo-1 antibodies exhibit a stronger inhibition of HisRS if the enzyme has been preincubated with tRNA His .…”

Cloning, sequencing and bacterial expression of human glycine tRNA synthetase

“…Bacterial expression of the GlyRS gene product serum (7,13). The 90 kDa biotinylated GlyRS fusion protein was immunoprecipitated from bacterial extract with EJ serum and…”

Autoantibodies in Connective Tissue Diseases. Clinical Significance and Analysis of Target Autoantigens.

“…African American and Latin American patients are reported to reveal a higher reactivity (20-40%) to U3RNP. Anti-U3RNPare associated with diffuse cutaneous scleroderma but not with obvious internal organ involvements (24 Anti-Jo-1 (histidyl-tRNA synthetase) antibodies Anti-Jo-1 antibodies are the first well-characterized autoantibodies in PM/DM, and are the most commonmyositis-specific autoantibodies found in 20-30% of PM/DMpatients in all ethnic and geographic populations (27,28). Although antiJo-1 is detected by standard Ouchterlony double immunodiffusion, it can also be detected by immunoprecipitation assay in whichsera containing anti-Jo-1 immunoprecipitate a distinct tRNAfor histidine (tRNAHis) and a 50 kDa protein from HeLacell extracts.…”

“…Patients with anti-Jo-1 reveal the characteristic clinical manifestations. These features include polymyositis, chronic pulmonary fibrosis, polyarthritis, and although less frequent, Raynaud' s phenomenon (28,31,32). Pulmonary fibrosis is likely to precede myositis in some patients, and vice versa in other patients (31).…”