Autoantibody reactive with three classes of RNA polymerases in sera from patients with systemic sclerosis.

260

225

Objective. To clarify the clinical features and prognosis of systemic sclerosis (SSc) based on serum antinuclear antibodies (ANA). Methods. We studied 275 consecutive Japanese patients newly diagnosed as having SSc, who were first evaluated during the period 1971—1990. Eight SSc–related ANA were identified using indirect immunofluorescence, double immunodiffusion, or immunoprecipitation assays. Clinical and prognostic features were retrospectively analyzed in patient groups, categorized by their serum ANA. Results. Cumulative survival rates at 10 years after diagnosis of SSc were 93% in patients with anticentromere antibodies (ACA), 72% in those with anti—U1 RNP, 66% in those with anti—DNA topoisomerase I (anti—topo I), and 30% in those with anti‐RNA polymerases I, II, and III (anti‐RNAP). Major organ involvement linked to cause of death included biliary cirrhosis in patients with ACA, isolated pulmonary arterial hypertension and cerebral hemorrhage in those with anti—U1 RNP, pulmonary interstitial fibrosis in those with anti—topo I, and cardiac and renal involvement in those with anti‐RNAP. Conclusion. Determinations of serum ANA in SSc patients are useful in predicting organ involvement and long‐term outcome.

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Clinical and Prognostic Associations Based on Serum Antinuclear Antibodies in Japanese Patients with Systemic Sclerosis

Kuwana

Kaburaki

Okano

et al. 1994

260

225

“…These SSc-associated antibodies are useful in the diagnosis of SSc and classification of patients, and thus are widely used in clinical settings (1,2). In addition, sera from a subset of SSc patients recognize 1 or more subtypes of RNA polymerase (RNAP) (2)(3)(4). Autoantibodies to RNAP I and RNAP III always coexist, and this pattern of antibody response is highly specific for SSc (2)(3)(4).…”

mentioning

confidence: 99%

Enzyme‐linked immunosorbent assay for detection of Anti–RNA polymerase III antibody: Analytical accuracy and clinical associations in systemic sclerosis

Kuwana

Okano

Pandey

et al. 2005

Objective. We have recently developed an enzymelinked immunosorbent assay (ELISA) for detection of anti-RNA polymerase III (anti-RNAP III) antibody, using a recombinant fragment containing the immunodominant epitope as the antigen source. This study was conducted to assess the analytical accuracy and clinical associations of the anti-RNAP III ELISA in patients with systemic sclerosis (SSc).Methods. To evaluate analytical sensitivity and specificity of the ELISA, both immunoprecipitation tests and ELISA were used to detect anti-RNAP III antibody in 534 SSc sera from patients at 3 medical centers. Sera from 522 SSc patients and 516 controls, including patients with other connective tissue diseases and blood bank donors, were also evaluated to assess the clinical sensitivity and specificity of the ELISA. Clinical findings in anti-RNAP III antibody-positive SSc patients were compared between patient groups stratified according to anti-RNAP III antibody levels determined by the ELISA.Results. In SSc patients, our ELISA showed analytical sensitivity of 91% and analytical specificity of 99% compared with the immunoprecipitation assay (a gold standard for detection of anti-RNAP III antibody). The additional analysis using a large series of SSc and control sera showed that clinical sensitivity and specificity of the ELISA with respect to the diagnosis of SSc were 17% and 98%, respectively. A high level of anti-RNAP III antibody was associated with diffuse cutaneous SSc, higher maximum total skin score, and increased frequency of tendon friction rubs.Conclusion. The anti-RNAP III ELISA is analytically accurate and clinically specific. With this assay, testing for anti-RNAP III antibody can be made routinely available.

“…tween hnRNPs and RNA polymerase, since some hnRNP proteins assemble on RNA polymerase I1 transcripts as soon as they are synthesized (1,35) and autoantibodies to RNA polymerases occur specifically in SSc (36,37). We believe that studies on the association of anti-hnRNP I with different SSc-associated autoantibodies might provide new insights on co-localization and function of the hnRNP I protein.…”

Section: Discussionmentioning

confidence: 92%

Identification of autoantibodies to the I protein of the heterogeneous nuclear ribonucleoprotein complex in patients with systemic sclerosis

Montecucco

Caporali

Cobianchi

et al. 1996

Objective. To assess the presence of autoantibodies to the I protein (polypyrimidine‐tract binding protein) of the heterogeneous nuclear RNPs (hnRNP) in different connective tissue diseases. Antibodies to other hnRNP proteins (A1, A2, and B) have been previously found in patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCTD).Methods. Sera from 101 patients with various connective tissue diseases and 25 normal controls were investigated by enzyme‐linked immunosorbent assay and immunoblotting, for their reactivity to highly purified recombinant hnRNP I. Moreover, reactivity to cellular hnRNP I protein was investigated by immunoblotting using a partially purified preparation of hnRNP proteins (including A1, A2, B, and I), and by indirect immunofluorescence. For the analysis of the fluorescence pattern, affinity‐purified antibodies to hnRNP I, obtained from a selected patient, were tested on HEp‐2 cells.Results. By immunoblotting, antibodies reacting to recombinant hnRNP I were found in 22 of 40 patients with systemic sclerosis (SSc), 3 of 32 with RA, 0 of 23 with SLE, and 0 of 6 with MCTD. Antibodies to recombinant hnRNP I were more frequently found in patients with pre‐SSc or limited SSc (15 of 24) than in those with intermediate or diffuse SSc (7 of 16). In indirect immunofluorescence studies, affinity‐purified anti—hnRNP I autoantibodies gave a diffuse nucleoplasmic staining. Using an hnRNP preparation from nuclear extracts, anti—hnRNP I reactivity was detectable in SSc sera, while it was not detectable in RA, SLE, and MCTD sera reacting with hnRNP A/B proteins.Conclusion. Human autoimmune sera show distinct patterns of anti‐hnRNP reactivity, i.e., anti‐A/B in SLE and RA sera, and anti‐I in SSc sera. This suggests that A/B proteins and the I protein may be involved in different dynamic hnRNP complexes that elicit different autoimmune responses. From a clinical perspective, anti—hnRNP I antibodies are frequently associated with pre‐SSc features, suggesting an early appearance of these antibodies during the course of the disease.