Frequency of disease-associated and other nuclear autoantibodies in patients of the German network for systemic scleroderma: correlation with characteristic clinical features

Abstract

IntroductionIn the present study, we analysed in detail nuclear autoantibodies and their associations in systemic sclerosis (SSc) patients included in the German Network for Systemic Scleroderma Registry.MethodsSera of 863 patients were analysed according to a standardised protocol including immunofluorescence, immunoprecipitation, line immunoassay and immunodiffusion.ResultsAntinuclear antibodies (ANA) were detected in 94.2% of patients. In 81.6%, at least one of the autoantibodies highly associated with SSc or with overlap syndromes with scleroderma features was detected, that is, anti-centromere (35.9%) or anti-topoisomerase I (30.1%), followed in markedly lower frequency by antibodies to PM-Scl (4.9%), U1-ribonucleoprotein (U1-RNP) (4.8%), RNA polymerases (RNAPs) (3.8%), fibrillarin (1.4%), Ku (1.2%), aminoacyl-transfer RNA synthetases (0.5%), To (0.2%) and U11-RNP (0.1%). We found that the simultaneous presence of SSc-associated autoantibodies was rare (1.6%). Furthermore, additional autoantibodies were detected in 55.4% of the patients with SSc, of which anti-Ro/anti-La, anti-mitochondrial and anti-p25/p23 antibodies were most frequent. The coexistence of SSc-associated and other autoantibodies was common (43% of patients). SSc-associated autoantibodies disclosed characteristic associations with clinical features of patients, some of which were previously not acknowledged.ConclusionsThis study shows that five autoantigens (that is, centromere, topoisomerase I, PM-Scl, U1-RNP and RNAP) detected more than 95% of the known SSc-associated antibody responses in ANA-positive SSc patients and characterise around 79% of all SSc patients in a central European cohort. These data confirm and extend previous data underlining the central role of the determination of ANAs in defining the diagnosis, subset allocation and prognosis of SSc patients.

Second generation analysis of antinuclear antibody (ANA) by combination of screening and confirmatory testing

“…Recently, ANA detection has been confirmed as the first level test for the serology of SARD by an international expert panel [1]. As a matter of fact, classical ANA testing requires the characterization of positive ANA findings by immunoassays for the detection of specific autoAbs to nuclear and cytoplasmic autoantigenic targets in the framework of the recommended two-tier approach [30][31][32]. However, this diagnostic two-step process has proved to be laborious and created constraints in particular for larger laboratories with high throughput [16,30].…”

Prevalence of Anti–RNA Polymerase III Antibodies in Systemic Sclerosis: New Data From a French Cohort and a Systematic Review and Meta‐Analysis

“…We have extrapolated this number from the total number of patients analyzed for antinuclear antibodies. Therefore, prevalence of anti-RNAP III may have been underestimated in these studies (30)(31)(32)(33)36,38,43). To address this issue, Supplementary Table 1 (available on the Arthritis & Rheumatology web site at http://onlinelibrary.wiley.com/ doi/10.1002/art.38219/abstract) shows the results of the quality evaluation.…”

Four Cases of Anti-PM/Scl Antibody-positive Juvenile Overlap Syndrome with Features of Myositis and Systemic Sclerosis

“…Indeed, these cases illustrate the extended period of time often needed to diagnose these patients and the key role of anti-PM/Scl antibodies in confirming the diagnosis. This antibody correlates strongly with the syndrome 8,9 and results in a nucleolar antinuclear antibody pattern 8,10 . Although it can be observed in isolated DM/JDM or SSc, 80% of patients with anti-PM/Scl antibodies will have overlap SSc/myositis syndrome 4 .…”