SLE Panel (includes ANA, dsDNA, Ro, La, Sm, RNP70, Ribo P)

Antinuclear antibodies (ANA) are a diverse group of autoantibodies that recognize nuclear macromolecules and their complexes. The presence of ANA is associated with various rheumatic diseases, including systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), systemic sclerosis (SSc), primary Sjogren’s syndrome, and idiopathic inflammatory myopathies (IIMs).

ANA positivity with a titer of >/=80 is one of the diagnostic criteria for SLE. The interpretation of Hep-2 IIF results is dependent on the titer and pattern. A titer of 80 has a sensitivity of 98% and specificity of 75% for SLE diagnosis (the steering committee for the 2019 SLE classification criteria). ANA can be present in patients with non-rheumatic diseases and in healthy individuals. A nuclear fine dense fine speckled (DFS70) pattern on HEp-2 can sometimes be observed in 1-8% of healthy individuals. A negative test does not rule out diseases associated with certain antibodies such as SSA/Ro60, Ro52, ribosomal P, Jo1 and some IIM-associated autoantibodies. The American College of Rheumatology (ACR) recommends testing for disease-specific autoantibodies when positive ANA titer and clinical suspicion of disease are present.

The antibody pattern can sometimes provide useful information about the disease diagnosis (www.anapatterns.org;ANA Patterns). The more commonly observed nuclear patterns in SLE are speckled (fine or coarse), and homogeneous.

Anti-double stranded DNA (dsDNA) antibodies have a high specificity (92% to 96%) and moderate sensitivity (57%-67%) for SLE. These antibodies constitute a criterion for SLE classification recommended by ACR and may be associated lupus nephritis.

Although less common (sensitivity, 26% to 31%) antibodies to Sm antigen are specific (95% to 99%) for SLE. Detection of Sm is a useful diagnostic marker in patients with SLE but without anti dsDNA antibodies (15% of patients).

Antibodies to SS-A/Ro are found in 25%-35% of ANA-positive SLE patients and 40%-60% of patients with Sjogren syndrome. Clinical or genetic associations with anti-Ro (SS-A) include photosensitive skin rash (lupus), interstitial pneumonia (lupus) , nephritis (lupus), T-cell receptor gene (lupus), vasculitis (Sjogren’s syndrome), thrombocytopenia in lupus, Sjogren’s syndrome or subacute cutaneous LE (SCLE) and primary biliary cirrhosis. SS-A/Ro and SS-B/La have been reported in patients with clinical features of SLE but are ANA-negative.

Antibodies to SS-B antigen are present in 5%-15%% of patients with SLE and 60% of patients with Sjogren syndrome with sicca complex. SS-B antibodies are almost always present simultaneously with SS-A while SS-A can occur alone. Patients with both SS-A and SS-B antibodies generally have milder disease and a lower incidence of lupus nephritis. and are associated with a lower prevalence of renal disease compared to patients with SS-A being positive alone.

Anti-ribosomal P antibodies are highly specific for SLE. The prevalence of ribosomal antibodies in SLE has been reported to range between 8 – 35%. These antibodies are found in 90% of patients with lupus psychosis. By IIF on HEp-2 cells, ribosomal antibodies produce a finely granular cytoplasmic pattern.
Anti RNP antibodies are found in patients with mixed connective tissue disease (MCTD) and SLE. Clinical sensitivity in SLE is between 8% to 69% with specificity between 25% to 82%. RNP antibodies almost always are demonstrable in patients who have anti-Sm antibodies. Anti- RNP antibodies also may occur in a small fraction of patients with Sjogren’s syndrome , rheumatoid arthritis , scleroderma, and polymyositis.

Select References:
1. Bossuyt, X., De Langhe, E., Borghi, M. O., & Meroni, P. L. Understanding and interpreting antinuclear antibody tests in systemic rheumatic diseases. Nature Reviews Rheumatology. 2020; 16(12): 715-726.
2. Jog NR, James JA. Biomarkers in connective tissue diseases. J Allergy Clin Immunol. 2017;140(6):1473-1483
3. Didier K, Bolko L, Giusti D, Toquet S, Robbins A, Antonicelli F, Servettaz A. Autoantibodies Associated With Connective Tissue Diseases: What Meaning for Clinicians? Front Immunol. 2018;9:541.
4. Aringer Met al.2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Arthritis Rheumatol. 2019;71:1400–1412
5. Aringer Met al.2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis. 2019;78:1151–1159 (2019).
6. Tan EM et al. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982;25:1271–1277
7. Damoiseaux J, Andrade LEC, Carballo OG, et al. Clinical relevance of HEp-2 indirect immunofluorescent patterns: the International Consensus on ANA patterns (ICAP) perspective. Ann of the Rheum Dis 2019;78:879-889.