Systemic Sclerosis Antibodies

  • Indicated when suspicion for SSc is high and patient presents with features of overlap syndrome
  • Individual tests in panel may be ordered separately. (See Related Tests.)
  • Indicated for patients with distinct features of SSc
  • Negative results do not rule out SSc; if test is negative and suspicion for SSc is high, consider testing for U3 RNP (fibrillarin), PM/Scl-100, U1RNP, Th/Tho, or other connective tissue disease autoantibodies based on patient’s clinical presentation

Systemic sclerosis (SSc), also called scleroderma, is a chronic autoimmune disorder characterized by fibrosis of the skin and various organs.   Early diagnosis and classification are important so that patients can be evaluated for organ involvement and/or damage.  However, because SSc is a heterogeneous disease, clinical presentation and disease course vary, and manifestations may overlap with those of other rheumatic disorders, all of which can complicate diagnosis.    The initial testing strategy includes CBC with platelet count and automated differential and nuclear antibody (ANA) by IFA, IgG. Confirmatory or secondary testing should be performed based on ANA IFA patterns (centromere, nucleolar, and speckled patterns), clinical presentation, and/or ethnicity.

Disease Overview

Prevalence

0.3-2.8/100,000 worldwide 

Age of Onset

20-50 years of age 

Sex

M<F, 1:3 

Diagnostic Issues

Autoimmune connective tissue diseases may present with similar features, particularly early in disease, making diagnosis difficult. The following considerations may assist in determining a diagnosis of SSc:

  • ANA IFA patterns may help define diagnostic pathways
    • Most patients with SSc will have either :
      • Centromere antibodies
      • Scl-70 antibodies
      • RNA polymerase III antibodies
    • These three antibody tests are required for the initial evaluation of SSc although the use of other autoantibody markers may improve diagnostic sensitivity for disease
  • The presence of SSc-specific antibodies may help predict disease phenotypes, which include:
    • CREST (calcinosis, Raynaud phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasia) syndrome: antibodies against centromere are most common 
    • Diffuse cutaneous SSc: antibodies against Scl-70 and RNA polymerase III most common
  • Antibody patterns may differ by ethnicity 
    • Antibodies against U3-RNP are more common in African Americans
    • Th/To autoantibodies are more common in Caucasians with limited cutaneous SSc

Test Interpretation

Clinical Sensitivity 

  • ANA by IFA for SSc: 90-95%
  • Individual SSc-specific marker: may vary based on ethnicity

Results

  • ANA patterns (including centromere) are reported
  • If positive, pattern and titers are reported

Limitations

  • Negative antibody test result does not exclude SSc (5-10% of patients with SSc are ANA IFA negative)  
  • Panel does not include Th/To

References