Evaluation of Patients With Systemic Sclerosis Without Specific or Associated Autoantibodies (SCLERONAB)

Phenotypic Evaluation of Patients With Systemic Sclerosis Without Specific or Associated Autoantibodies

Systemic sclerosis (SSc) is a complex systemic autoimmune disease with variable phenotype and prognosis. Autoantibodies are important diagnostic biomarkers in SSc. More than 90% of patients with SSc had anti-nuclear antibodies. Autoantibodies specific to SSc (anti-topoisomerase I antibodies, anti-centromeres, anti-RNA polymerase III, anti-Th/To, anti-fibrillarin, anti-NOR90) or associated with overlap syndromes (anti-RNA polymerase III antibodies -PM/Scl, anti-KU, anti-U1RNP, anti-TRIM21) are detected in most patients. Excluding anti-TRIM21 antibodies, autoantibodies are usually mutually exclusive and are associated with distinct phenotypes.

Around 5 to 10% of patients with SSc have no autoantibodies detectable with routine biological tests. Recently, new autoantibody specificities have been described in SSc (anti-eIF2B, anti-RuvBL1/2, anti-BICD2, anti-U11/U12 RNP antibodies).

"Seronegative" patients could represent new specificities of autoantibodies (unknown or not currently routinely evaluated) associated with different phenotypes of the disease.

Primary objective is to compare the phenotype of patients with systemic sclerosis with or without detectable specific or associated autoantibodies.

Secondary objectives are:

• to determine homogeneous groups of patients with systemic sclerosis without detectable specific or associated autoantibodies
• to compare the phenotype of patients with systemic sclerosis without detectable specific or associated autoantibodies according to anti-nuclear antibodies status

Study Overview

• Status: Not yet recruiting
• Conditions: Systemic Sclerosis
• Intervention / Treatment: Other: disease phenotype

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Paul Decker, MD; Phone Number: +33383157240; Email: p.decker@chru-nancy.fr

Study Locations

• France
  • Angers, France
    • Chu Angers
    • Contact: Christian Lavigne
  • Brest, France
    • Chu Brest
    • Contact: Claire De Moreuil
  • Dunkerque, France
    • CH Dunkerque
    • Contact: Amélie Leurs
  • Grenoble, France
    • CHU Grenoble
    • Contact: Alban Deroux
  • Lille, France
    • CHU Lille
    • Contact: David Launay
  • Lyon, France
    • Hospices Civils De Lyon
    • Contact: Claire Grange
  • Marseille, France
    • AP-HM
    • Contact: Brigitte Granel
  • Nice, France
    • CHU Nice
    • Contact: Viviane Queyrel
  • Paris, France
    • APHP
    • Contact: Benjamin Chaigne
  • Poitiers, France
    • Chu Poitiers
    • Contact: Mickaël Martin
  • Reims, France
    • CHU Reims
    • Contact: Amélie Servettaz
  • Rennes, France
    • Chu Rennes
    • Contact: Alain Lescoat
  • Strasbourg, France
    • Hopitaux Universitaires de Strasbourg
    • Contact: Emmanuel Chatelus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients followed in internal medicine or rheumatology units until December 2021

Description

Inclusion Criteria:

• Patient with systemic sclerosis defined according to ACR/EULAR 2013 classification criteria
• Patient with a minimum follow-up of 3 years since the diagnosis of systemic sclerosis
• Patient evaluated for the following systemic sclerosis specific and/or associated autoantibodies: anti-topoisomerase I, anti-centromere, anti-RNA polymerase III (RP155 and RP11), anti-Th/To antibodies , anti-fibrillarin, anti-NOR90, anti-PM/Scl, anti-KU, anti-U1RNP and anti-SSA antibodies (independently of antinuclear antibodies status)

Exclusion Criteria:

• Patient with equivocal results for one or more systemic sclerosis specific and/or associated autoantibodies
• Patient initially negative but with a positive result for systemic sclerosis specific and/or associated autoantibodies during follow-up

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
SSc patients without specific or associated autoantibodies ("seronegative" patients)	Other: disease phenotype; evaluation of SSc phenotypes
SSc patients with specific or associated autoantibodies	Other: disease phenotype; evaluation of SSc phenotypes

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
diagnosis time	duration between date of first symptom (excluding Raynaud's phenomenon) and SSc diagnosis	baseline (J0)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
number of patients with scleroderma	sine scleroderma (no scleroderma), limited scleroderma or diffuse scleroderma	baseline (J0)
number of patients with raynaud's phenomenon		baseline (J0)
number of patients with digital ulcers		baseline (J0), 3 years of follow-up and through study completion (an average of 5 years)
number of patients with calcinosis		baseline (J0), 3 years of follow-up and through study completion (an average of 5 years)
number of patients with telangiectases		baseline (J0)
number of patients with articular involvement		baseline (J0), 3 years of follow-up and through study completion (an average of 5 years)
number of patients with muscular involvement		baseline (J0), 3 years of follow-up and through study completion (an average of 5 years)
number of patients with cardiac involvement		baseline (J0), 3 years of follow-up and through study completion (an average of 5 years)
number of patients with interstitial lung disease		baseline (J0), 3 years of follow-up and through study completion (an average of 5 years)
number of patients with pulmonary arterial hypertension		baseline (J0), 3 years of follow-up and through study completion (an average of 5 years)
number of patients with scleroderma renal crisis		baseline (J0), 3 years of follow-up and through study completion (an average of 5 years)
number of patients with gastrointestinal involvement		baseline (J0), 3 years of follow-up and through study completion (an average of 5 years)
modified Rodnan skin score		baseline (J0), 3 years of follow-up and through study completion (an average of 5 years)
forced vital capacity (FVC)	%predicted FVC values	baseline (J0), 3 years of follow-up and through study completion (an average of 5 years)
diffusing capacity for carbon monoxide (DLCO)	%predicted DLCO values	baseline (J0), 3 years of follow-up and through study completion (an average of 5 years)
rate of patients without death		3 years and 5 years of follow-up

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France

Study record dates

Study Major Dates

• Study Start (Estimated): September 2, 2024
• Primary Completion (Estimated): June 29, 2025
• Study Completion (Estimated): June 29, 2025

Study Registration Dates

• First Submitted: May 6, 2024
• First Submitted That Met QC Criteria: May 8, 2024
• First Posted (Actual): May 14, 2024

Study Record Updates

• Last Update Posted (Actual): May 14, 2024
• Last Update Submitted That Met QC Criteria: May 8, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Connective Tissue Diseases; Sclerosis; Scleroderma, Systemic; Scleroderma, Diffuse
• Other Study ID Numbers: 2024PI015

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No