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

Abstract

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.

Autoantibodies to fibrillarin in systemic sclerosis (scleroderma). An immunogenetic, serologic, and clinical analysis

“…This study also confirms that antifibrillarin antibodies occur more frequently in blacks than whites (6,14,17); 16% of black SSc patients overall and 60% of those with ANoA were positive for antifibrillarin in this series. Hispanic-Americans with SSc also may show a higher frequency of this autoantibody; however, the number of such patients in this study was too small to adequately assess an association.…”

“…In addition, as reported previously (4,14), males were again overrepresented among antifibrillarinpositive patients compared with their negative counterparts. The majority of antifibrillarin-positive patients had diffuse cutaneous scleroderma, as previously reported (6,14), and differed significantly only from ACApositive patients with respect to this clinical feature. In contrast, cardiac, renal, and gastrointestinal involvement were strongly correlated with the presence of antifibrillarin antibodies when compared with several individual autoantibody subgroups as well as with the group of antifibrillarin-negative patients overall (Table 2).…”

“…In fact, earlier studies have found both black race and male sex, as well as renal, cardiac, and pulmonary involvement, to be poor prognostic signs in SSc (46,47). As autoantibody subgroups of SSc have evolved, more recent studies have indicated that anti-RNA polymerase-and anti-top0 I antibody-positive patients have worse prognoses than other SSc patients, especially those with ACA (6,15). Antifibrillarin-positive patients, however, have not been considered in these studies, probably because of the low prevalence of this antibody.…”

Association of hepatocyte growth factor promoter polymorphism with severity of interstitial lung disease in Japanese patients with systemic sclerosis

“…The criteria used to define individual organ involvement have been described elsewhere (15). ILD was defined as the presence of bibasilar reticulation and/or fibrosis on chest radiograph.…”

“…Serum samples from all SSc patients were analyzed for anticentromere, antitopo I, and anti-U1 small nuclear RNP (anti-U1 snRNP) antibodies, which are major SSc-related ANAs in the Japanese population (15), using indirect immunofluorescence and immunoprecipitation assays (15).…”