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

Abstract

Objective. Studies assessing the prevalence of anti-RNA polymerase III (anti-RNAP III) antibodies in systemic sclerosis (SSc) have yielded a wide range of results. The aim of the present study was to describe a new SSc cohort tested for presence of anti-RNAP III and perform a systematic review and meta-analysis to assess the prevalence of anti-RNAP III in patients worldwide and the potential factors of variability.Methods. Seropositivity for anti-RNAP III was evaluated in a French cohort of SSc patients. A systematic review of the literature was carried out in PubMed and EMBase. Meta-analysis was performed using available data on prevalence, clinical characteristics of SSc patients, and the types of assays used for anti-RNAP III testing.Results. One hundred thirty-three French SSc patients were tested for anti-RNAP III, and a prevalence of 6-9% was found in these patients. Thirty studies representing a total population of 8,437 SSc patients were included in the meta-analysis. Prevalence of anti-RNAP III in this population was highly variable (range 0-41%). The overall pooled prevalence of anti-RNAP III was 11% (95% confidence interval 8-14), but heterogeneity was high among studies (I 2 ‫؍‬ 93%, P < 0.0001). Geographic factors such as continent or country of study origin partially explained this heterogeneity and correlated with the prevalence. No other baseline SSc characteristics were significantly correlated with the prevalence of anti-RNAP III.Conclusion. Data on our new cohort and our meta-analysis of the literature confirmed that anti-RNAP III prevalence in SSc varies among centers. Geographic factors were significantly associated with prevalence, which underscores the probable implication that genetic background and environmental factors play a role. Heterogeneity among studies remained largely unexplained.

Are autoantibodies to RNA-polymerase III to be incorporated in routine diagnostic laboratory algorithms for systemic autoimmune rheumatic diseases?

“…Bonroy et al recently calculated that in routine laboratory settings a patient/control ratio of 0.002 is realistic,2 that is, only 2 out of each 1000 patients being suspected for SARD, and thus are tested for autoantibodies according to local algorithms, eventually are diagnosed with SSc. The ARA prevalence in SSc is about 11% (95% CI 8% to 14%; being in line with data obtained in the validation cohort),3 while the specificity of the distinct test systems varies between 99.0% and 99.5% 4 5. Taking these data together, at least 25× more false-positive ARA results are to be expected than true positives.…”

Autoantibodies in Systemic Sclerosis: Spectrum, Clinical Associations, and Prognostic Value

“…Частота выявления АРНКП колеблется в широких пределах и в среднем со-ставляет 4-6% [66]. Она высока у европеоидов в США и Великобритании (20-25%) и низка во Франции (5%) [67]. В большой японской когорте АРНКП III при ССД выявлялись методом ИФА в 10,7% случаев, при других РЗ -в 1,2% и не выявлялись у здоровых [68].…”

“…Частота обнаружения АРНКП III зависела от географических факторов. Вероятно, появление этих аутоАТ определяется как генетической предрасположен-ностью, так и влиянием окружающей среды [67]. Наличие этих аутоАТ ассоциируется с носительством HLA-DRB1*0301.…”

A To-Do List at Diagnosis of Systemic Sclerosis with Positive Anti-RNA Polymerase III Antibodies

“…In Northern Europe and North America, about 60% of patients experiencing SRC carry anti-RNAP III antibody 7 . Lower incidence of SRC in Japan, France, and Mediterranean countries is thought to reflect the lower prevalence of anti-RNAP III antibody within these populations when compared with the UK and North America 8 . Despite the lower prevalence of anti-RNAP III antibody in French and Japanese SSc patients, this antibody remains the strongest serological marker for SRC 8,9 .…”

“…Lower incidence of SRC in Japan, France, and Mediterranean countries is thought to reflect the lower prevalence of anti-RNAP III antibody within these populations when compared with the UK and North America 8 . Despite the lower prevalence of anti-RNAP III antibody in French and Japanese SSc patients, this antibody remains the strongest serological marker for SRC 8,9 . On the other hand, analysis involving a large number of patients revealed clinical features potentially associated with anti-RNAP III antibodies, which were previously unnoticed.…”