Anti-Th/To Are Common Antinucleolar Autoantibodies in Italian Patients with Scleroderma

Objective.Patients with scleroderma (systemic sclerosis; SSc) can be classified into subsets based on autoantibody profile and clinical features. Specificities such as anti-Th/To and anti-fibrillarin (U3RNP) are detectable mainly by immunoprecipitation (IP), which is not widely used in clinical laboratories. We examined the autoantibody profiles and clinical manifestations in a cohort of Italian patients with SSc, focusing on anti-Th/To and anticentromere (ACA) antibodies, associated with limited cutaneous SSc (lcSSc).Methods.Sera from 216 consecutive patients with SSc were tested for ACA (by indirect immunofluorescence), antitopoisomerase I (topo I; by counterimmunoelectrophoresis), and anti-RNA polymerase III (RNAPIII; by ELISA). Forty-one sera negative for these specificities were tested by IP analysis of proteins (35S-methionine labeled K562 cell extract) and RNA (silver staining).Results.Among 216 SSc patients analyzed, anti-topo I, ACA, and anti-RNAPIII were detected in 38% (81/216), 31% (67/216) and 7% (15/216), respectively. Among 41 sera negative for ACA, anti-topo I, and anti-RNAPIII and which were tested by IP, 14 were nucleolar stain-positive. Eight out of 14 (57%) showed anti-Th/To reactivity, but no anti-U3RNP was found. In comparison with ACA-positive patients, anti-Th/To-positive patients were younger (p = 0.0046) and more commonly were male (p = 0.0006). All 8 anti-Th/To-positive and all but one ACA-positive patients had lcSSc. Interstitial lung disease (ILD) and pericarditis were more frequent in anti-Th/To-positive patients.Conclusion.Anti-Th/To are common in antinucleolar antibody-positive Italian patients with SSc. Anti-Th/To and ACA patients had lcSSc, with excellent prognosis. The anti-Th/To group had frequent pericarditis and ILD, although impairment of pulmonary function appeared mild.

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RNA Polymerase III Antibody Positive Systemic Sclerosis with Cystic Interstitial Lung Disease and Pulmonary Hypertension

10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a3118 ◽

2019 ◽

Author(s):

A. Abdou ◽

A. Kotecha ◽

M. Mandeel ◽

V. Hannosh ◽

G. Krishnamoorthy

Keyword(s):

Pulmonary Hypertension ◽

Systemic Sclerosis ◽

Interstitial Lung Disease ◽

Rna Polymerase ◽

Lung Disease ◽

Rna Polymerase Iii ◽

Polymerase Iii

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Anti-RNA Polymerase III Antibody Prevalence and Associated Clinical Manifestations in a Large Series of French Patients with Systemic Sclerosis: A Cross-sectional Study

The Journal of Rheumatology ◽

10.3899/jrheum.090677 ◽

2009 ◽

Vol 37 (1) ◽

pp. 125-130 ◽

Cited By ~ 41

Author(s):

OLIVIER MEYER ◽

LUC DE CHAISEMARTIN ◽

PASCALE NICAISE-ROLAND ◽

JEAN CABANE ◽

FLORENCE TUBACH ◽

...

Keyword(s):

Systemic Sclerosis ◽

Rna Polymerase ◽

Topoisomerase I ◽

Rna Polymerase Iii ◽

Laboratory Data ◽

Clinical Manifestations ◽

The United States ◽

Cutaneous Disease ◽

Polymerase Iii ◽

Renal Crisis

Objective.To determine the prevalence of anti-RNA polymerase III autoantibodies in French patients with systemic sclerosis (SSc) and to identify the associated clinical manifestations.Methods.Consecutive patients with SSc seen in 3 tertiary centers in Paris were included. Sera samples were collected together with the relevant clinical and immunological data. Anti-RNA polymerase III antibodies were detected by ELISA at a central laboratory. Data on other antibodies were abstracted from the medical records.Results.We included 319 patients: 84% women, 36% with a diffuse cutaneous subtype, 44% with pulmonary fibrosis, 5% with pulmonary hypertension, 4% with renal crisis, among whom 29 (9.4%) had anti-RNA polymerase III antibodies. These antibodies were more prevalent in patients with diffuse than with limited cutaneous disease (14.3% vs 6.0%; OR 2.6, 95% CI 1.2–5.48, p = 0.016). Renal crisis was more prevalent in patients with than in those without anti-RNA polymerase III antibodies (14% vs 3%; OR 5.0, 95% CI 1.4–17.3, p = 0.012). Renal crisis occurred in 2.2% of patients with anti-topoisomerase I and 3.9% of patients with anticentromere antibodies. Of the patients with anti-RNA polymerase III antibodies, 24 (83%) had no other systemic sclerosis-specific autoantibodies.Conclusion.The prevalence of anti-RNA polymerase III antibodies in French patients appeared to be lower than in the United States and similar to that in continental Europe. These antibodies were consistently associated with diffuse cutaneous disease and were the most common immunological marker for renal crisis. Anti-RNA polymerase III determination can help to risk-stratify SSc patients at high risk for this severe manifestation.

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A Unique Presentation of Anti-RNA Polymerase III Positive Systemic Sclerosis Sine Scleroderma

Case Reports in Rheumatology ◽

10.1155/2016/8536341 ◽

2016 ◽

Vol 2016 ◽

pp. 1-4

Author(s):

Cody M. Lee ◽

Diana Girnita ◽

Arundhati Sharma ◽

Surabhi Khanna ◽

Jean M. Elwing

Keyword(s):

Systemic Sclerosis ◽

Rna Polymerase ◽

Wide Spectrum ◽

Rna Polymerase Iii ◽

Clinical Manifestations ◽

Autoimmune Disorder ◽

Scleroderma Renal Crisis ◽

Polymerase Iii ◽

Digital Ischemia ◽

Pulmonary Arterial

Systemic sclerosis is a rare autoimmune disorder with a wide spectrum of clinical manifestations and a multitude of autoantibodies that are associated with it. In the past several years, advances in serologic testing have led to research indicating important prognostic and phenotypic associations with certain subsets of autoantibodies. In particular, anti-RNA polymerase III (anti-RNAP III) has been associated with diffuse cutaneous disease, scleroderma renal crisis, a temporal relationship with malignancy, myositis, synovitis, joint contractures, and gastric antral vascular ectasia. However, anti-RNAP III has not been associated with systemic sclerosis sine scleroderma. We describe a patient with an atypical presentation of anti-RNAP III positive systemic sclerosis sine scleroderma who presented without the typical features of anti-RNAP III disease. Instead, she presented with critical digital ischemia, pulmonary arterial hypertension, gastroesophageal reflux disease, interstitial lung disease, and no clinically detectable sclerodactyly.

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Systemic Sclerosis Sine Scleroderma: A Multicenter Study of 1417 Subjects

The Journal of Rheumatology ◽

10.3899/jrheum.140236 ◽

2014 ◽

Vol 41 (11) ◽

pp. 2179-2185 ◽

Cited By ~ 30

Author(s):

Sehriban Diab ◽

Nathaniel Dostrovsky ◽

Marie Hudson ◽

Solène Tatibouet ◽

Marvin J. Fritzler ◽

...

Keyword(s):

Systemic Sclerosis ◽

Interstitial Lung Disease ◽

Rna Polymerase ◽

Lung Disease ◽

Multicenter Study ◽

Research Group ◽

Rna Polymerase Iii ◽

Skin Involvement ◽

Anticentromere Antibodies ◽

Clinical Profiles

Objective.To describe the clinical and serological features of systemic sclerosis sine scleroderma (ssSSc) in a multicentered SSc cohort.Methods.Data from 1417 subjects in the Canadian Scleroderma Research Group registry were extracted to identify subjects with ssSSc, defined as SSc diagnosed by an expert rheumatologist, but without any sclerodactyly or skin involvement prior to baseline study visit or during followup. Clinical and serological features of ssSSc subjects were compared to limited (lcSSc) and diffuse cutaneous SSc (dcSSc) subjects.Results.At the first registry visit, only 57 subjects (4.0%) were identified as having ssSSc. Of these, 30 (2.1%) were reclassified as lcSSc within 1.9 years. Thus, only 27 ssSSc subjects (1.9%) remained, with mean followup of 2.4 years. Clinical profiles of ssSSc were generally similar or milder compared to lcSSc, and milder than dcSSc, including rates of interstitial lung disease (25.9% ssSSc, 25.4% lcSSc, 40.3% dcSSc). Patients with ssSSc had serological profiles similar to those with lcSSc, including high rates of anticentromere antibodies (50.0% ssSSc, 47.5% lcSSc, 12.1% dcSSc), and low rates of antitopoisomerase I (16.7% ssSSc, 7.0% lcSSc, 21.8% dcSSc) and anti-RNA polymerase III (0 ssSSc, 11.1% lcSSc, 34.9% dcSSc).Conclusion.The condition ssSSc is rare and resembles lcSSc. These observations suggest that ssSSc is most likely a forme fruste of lcSSc, and that the absence of skin involvement may in part be related to misclassification arising from early or subtle skin involvement. There is little evidence to consider ssSSc as a distinct clinical or serological subset of SSc.

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A Rare Case of Anti-RNA Polymerase III Autoantibody-Associated Interstitial Lung Disease in Systemic Sclerosis Sine Scleroderma

10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a3104 ◽

2019 ◽

Author(s):

W.S. Tam ◽

A.M. Nambiar

Keyword(s):

Systemic Sclerosis ◽

Interstitial Lung Disease ◽

Rna Polymerase ◽

Lung Disease ◽

Rare Case ◽

Rna Polymerase Iii ◽

Polymerase Iii

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Anti-RNA polymerase III antibodies in patients with suspected and definite systemic sclerosis: Why and how to screen

Journal of Scleroderma and Related Disorders ◽

10.1177/2397198318786158 ◽

2018 ◽

Vol 3 (3) ◽

pp. 214-220 ◽

Cited By ~ 1

Author(s):

Maria-Grazia Lazzaroni ◽

Paolo Airò

Keyword(s):

Systemic Sclerosis ◽

Rna Polymerase ◽

Topoisomerase I ◽

Rna Polymerase Iii ◽

Clinical Manifestations ◽

Enzyme Linked Immunosorbent Assay ◽

Scleroderma Renal Crisis ◽

American College Of Rheumatology ◽

Polymerase Iii ◽

European League Against Rheumatism

Anti-RNA Polymerase III antibodies are the most frequent anti-nuclear antibodies in systemic sclerosis, after anti-centromere and anti-Topoisomerase I. Considering their specificity for systemic sclerosis, they have been included in 2013 American College of Rheumatology/European League Against Rheumatism classification criteria for systemic sclerosis. They were first identified in 1993 using an immunoprecipitation method; the subsequent diffusion of commercial assays, based on the enzyme-linked immunosorbent assay or multiplex line immunoblot techniques, has allowed an increasing number of systemic sclerosis patients to be tested for this autoantibody; nevertheless, the diffusion of this test in systemic sclerosis patients is probably still sub-optimal. Anti-RNA Polymerase III antibodies have been associated with important clinical manifestations: rapid and diffuse cutaneous involvement, joint contractures, scleroderma renal crisis, gastric antral vascular ectasia and malignancies synchronous to systemic sclerosis onset. Moreover, other possible clinical associations, including pulmonary hypertension, still need confirmation. Since the correct approach for screening for anti- RNA Polymerase III antibodies in patients with suspected or definite systemic sclerosis is still debated, possible strategies are proposed here. Moreover, issues that are still controversial are discussed, including the interpretation of multiple simultaneous positivity for anti-RNA Polymerase III antibodies and other autoantibodies in line immunoassay, and the possible relevance of anti-RNA Polymerase III antibodies titre.

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