What further tests are recommended for a patient with a positive Antinuclear Antibody (ANA) screen and positive Ribonucleoprotein (RNP) antibody?

From the Guidelines

For a patient with a positive ANA screen and positive RNP antibody, further recommended tests include anti-dsDNA antibodies, anti-Smith antibodies, anti-SSA/Ro and anti-SSB/La antibodies, anti-Scl-70 antibodies, anti-centromere antibodies, and complement levels (C3 and C4). These recommendations are based on the most recent and highest quality study available, which emphasizes the importance of a comprehensive testing approach to differentiate between various connective tissue diseases associated with positive RNP antibodies, particularly mixed connective tissue disease (MCTD), systemic lupus erythematosus, systemic sclerosis, and polymyositis 1. The study also highlights the need for clinical information to guide laboratory testing, and the importance of using a standardized approach to ANA detection, with a cut-off point of 1:80 by the indirect immunofluorescence test on HEp-2 cells (IFI) 1. Some key points to consider when ordering further tests include:

• The use of a double-screening strategy for anti-dsDNA testing, using a last-generation SPA as the first step, followed by the CLIFT as the confirmation test 1
• The importance of reporting the method used for ANA detection, as well as the results obtained by each method, to ensure accurate interpretation of the results 1
• The need for organ-specific testing, depending on symptoms, such as pulmonary function tests for respiratory symptoms, echocardiogram for cardiac involvement, or muscle enzymes (CPK, aldolase) for muscle weakness
• The use of a complete blood count, comprehensive metabolic panel, urinalysis, and inflammatory markers like ESR and CRP to help establish the correct diagnosis and guide appropriate treatment. Overall, a comprehensive testing approach is crucial to establish the correct diagnosis and guide appropriate treatment for patients with positive ANA and RNP antibodies.

From the Research

Further Testing for Positive ANA and RNP Antibody

To determine the appropriate further testing for a patient with a positive Antinuclear Antibody (ANA) screen and positive Ribonucleoprotein (RNP) antibody, consider the following:

• The presence of anti-RNP antibodies can be associated with systemic lupus erythematosus (SLE) and other rheumatic diseases, as well as chronic liver diseases 2, 3.
• Specific ANAs, such as antibodies to Sm, double-stranded DNA (dsDNA), SSA/Ro60, and U1RNP, are included in classification criteria for various rheumatic diseases 4.
• The detection of anti-ENA antibodies, including anti-RNP, by enzyme-linked immunosorbent assay can be useful in predicting the diagnosis of SLE, particularly among patients who are positive for ANA and negative for anti-dsDNA 5.

Recommended Tests

Based on the available evidence, the following tests may be considered:

• Extractable nuclear antigen (ENA) panel to detect antibodies to Sm, dsDNA, SSA/Ro60, and other relevant antigens 4, 5.
• Liver function tests to evaluate for potential liver disease, although the presence of autoantibodies may not be related to liver function tests 3.
• Clinical evaluation for symptoms and signs of SLE and other rheumatic diseases, such as pleuritis, and consideration of hydroxychloroquine use 5.

Interpretation of Results

When interpreting the results of these tests, consider the following:

• The sensitivity and specificity of each assay, as well as the disease context and antibody level 4.
• The presence of anti-RNP antibodies, as well as other anti-ENA antibodies, can provide valuable information for the diagnosis and management of rheumatic diseases 2, 3, 5.