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

From the Guidelines

Extractable Nuclear Antigens (ENA) antibodies, specifically Anti-Ribonucleoprotein (RNP) and Anti-Smith antibodies, are indicative of Systemic Lupus Erythematosus (SLE).

Key Points

• The presence of Anti-RNP and Anti-Smith antibodies can be used as confirmatory tests when ANAs turn out positive during diagnosis, as recommended by expert panels 1.
• These antibodies are among the most common targets of autoantibodies detected in SLE, along with chromatin, ribosomal P protein, and others 1.
• The detection of ANA is the first level test for laboratory diagnosis of SARD, including SLE, and ANA testing should be accompanied by testing for anti-dsDNA and anti-ENA antibodies 1.
• A positive ANA test, particularly at a dilution of 1:160 or higher, increases the pre-test probability of SLE and warrants further testing, including anti-ENA antibodies such as anti-RNP and anti-Smith 1.
• The use of a double-screening strategy for anti-dsDNA testing, which includes a sensitive assay followed by a specific assay like CLIFT, can help minimize false positives and improve diagnostic accuracy 1.
• In cases where anti-dsDNA results are inconsistent or negative but clinical suspicion remains high, the detection of other antibodies such as antiphospholipid antibodies or anti-nucleosome antibodies can support the diagnosis of SLE 1.
• It is crucial for laboratories to standardize their assays and report methods used for detecting ANA, anti-dsDNA, and anti-ENA antibodies to ensure accurate interpretation of results 1.
• Clinical context and collaboration between clinicians and laboratory professionals are essential for the appropriate use and interpretation of autoantibody tests in the diagnosis and follow-up of SLE 1.

From the Research

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

• ENA antibodies, specifically Anti-Ribonucleoprotein (RNP) and Anti-Smith antibodies, have been studied in relation to SLE diagnosis and clinical characteristics 2, 3, 4, 5, 6
• Studies have shown that patients with anti-RNP antibodies often have overlapping features of SLE, progressive systemic sclerosis, and polymyositis, with a low incidence of nephritis 2, 3
• The presence of anti-Sm antibodies is often associated with anti-RNP antibodies, and this combination is commonly found in SLE patients 4
• Anti-ENA antibodies, including anti-RNP and anti-Sm, have been found to be useful predictors for the diagnosis of SLE, particularly among patients who are positive for antinuclear antibodies (ANA) and negative for anti-double-stranded DNA (anti-dsDNA) 5
• The combined use 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% 6

Clinical Characteristics of SLE Patients with ENA Antibodies

• SLE patients with anti-RNP antibodies tend to have a clinical and laboratory profile similar to that of the mixed connective tissue disease (MCTD) syndrome, with a low prevalence of nephritis and a high frequency of normal complement values 2
• Patients with anti-ENA antibodies, especially anti-Ro/SS-A, tend to have a higher incidence of pleuritis and are more likely to be treated with hydroxychloroquine 5
• The presence of anti-ENA antibodies, including anti-RNP and anti-Sm, is associated with a distinct clinical profile, but does not necessarily distinguish SLE from other rheumatic diseases 3, 4

Diagnostic Value of ENA Antibodies

• Anti-ENA antibodies, particularly anti-RNP and anti-Sm, are useful markers for the diagnosis of SLE, especially when used in combination with other clinical and laboratory criteria 2, 3, 4, 5, 6
• The diagnostic value of anti-ENA antibodies is enhanced when used in conjunction with other antibodies, such as anti-cardiolipin and anti-β2-glycoprotein 1 antibodies 6