Are Extractable Nuclear Antigens (ENA) antibodies, specifically Anti-Ribonucleoprotein (Anti-RNP) and Anti-Smith (Anti-Sm) antibodies, indicated in Systemic Lupus Erythematosus (SLE)?

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Last updated: February 13, 2025 • View editorial policy

From the Guidelines

Yes, Extractable Nuclear Antigens (ENA) antibodies, specifically Anti-Ribonucleoprotein (Anti-RNP) and Anti-Smith (Anti-Sm) antibodies, are indicated in Systemic Lupus Erythematosus (SLE).

Key Points

  • According to the international recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies 1, the detection of ANA is the first level test for laboratory diagnosis of SARD, and anti-ENA antibodies testing should be included in the autoantibodies detection as part of the diagnostic work-up of SARD.
  • The study recommends that in case of a positive ANA test during the diagnostic work-up, it is recommended to perform specific tests for anti-ENA antibodies, including Anti-RNP and Anti-Sm antibodies 1.
  • Another study also recommends confirmatory testing of anti-extractable nuclear antigens autoantibodies (anti-ENA) when ANAs turn out positive during diagnosis 2.
  • The most common targets of the autoantibodies detected in SLE include chromatin, ribosomal P protein, spliceosome small nuclear ribonucleoproteins (Smith), and U1-ribonucleoprotein, which supports the use of Anti-RNP and Anti-Sm antibodies in SLE diagnosis 2.

Testing Recommendations

  • The method used for anti-ENA antibody detection should be reported, and in case of discrepancy with IIFA or with clinical suspicion, the use of an additional method should be considered 1.
  • Results of assays for antibodies to specific ENA should be reported separately, including negative results 1.
  • Quantitative determination of positive anti-RNP antibodies is recommended in case of a clinical suspicion of mixed connective tissue disease 1.

From the Research

Extractable Nuclear Antigens (ENA) Antibodies in Systemic Lupus Erythematosus (SLE)

  • ENA antibodies, including Anti-Ribonucleoprotein (Anti-RNP) and Anti-Smith (Anti-Sm) antibodies, are associated with SLE 3, 4, 5, 6, 7
  • Studies have shown that patients with SLE often have a high frequency of anti-RNP antibodies, which can be used as a marker for the disease 3, 4, 6
  • The presence of anti-Sm antibodies is often accompanied by anti-RNP antibodies, suggesting a relationship between the two 4
  • Patients with anti-RNP antibodies tend to have a lower incidence of renal disease and a higher incidence of Raynaud's phenomenon, swollen hands, and hypergammaglobulinemia 3, 5
  • The combination of anti-ENA antibodies, anti-cardiolipin antibodies, and anti-β2-glycoprotein 1 antibodies has been shown to have high diagnostic value for SLE 7

Clinical Characteristics of Patients with Anti-RNP and Anti-Sm Antibodies

  • Patients with anti-RNP antibodies often have overlapping features of SLE, progressive systemic sclerosis, and polymyositis, and tend to have a low incidence of nephritis 3, 5
  • Patients with anti-Sm antibodies tend to have a more typical SLE presentation, with a higher incidence of Raynaud's phenomenon 5
  • The presence of anti-RNP and anti-Sm antibodies can be used to distinguish a subset of patients with SLE who have a distinct clinical and laboratory profile 3

Diagnostic Value of Anti-ENA Antibodies

  • Anti-ENA antibodies, including anti-RNP and anti-Sm antibodies, can be used as biomarkers for the diagnosis of SLE 6, 7
  • The combination of anti-ENA antibodies, anti-cardiolipin antibodies, and anti-β2-glycoprotein 1 antibodies has been shown to have high diagnostic value for SLE, with a sensitivity of 82.12% and a specificity of 80.03% 7

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.