ANA Screen, IFA, with Reflex to Titer and Pattern/Systemic Sclerosis Panel 1

This panel may be used as part of an initial diagnostic evaluation of individuals with clinical suspicion of systemic sclerosis (SSc). This panel starts with an immunofluorescence assay (IFA) to detect antinuclear antibodies (ANAs). A positive result will reflex to 3 individual autoantibodies (antibodies to Scl-70, centromere B, and RNA polymerase III) that are associated with SSc.

The laboratory evaluation for individuals with clinical suspicion of autoimmune diseases often begins with an ANA screen. The classic ANA IFA on human epithelial type 2 cells is considered by the American College of Rheumatology (ACR) as the current gold standard because of its overall high sensitivity for several autoimmune diseases [1]. ANAs can be detected in 90% to 95% of the patients with SSc; a negative ANA IFA result decreases the likelihood of SSc but does not exclude it. Knowing fluorescent staining patterns of an ANA IFA can be helpful in the differential diagnosis and guide selection of further testing for specific autoantibodies [2].

Antibodies to centromere, Scl-70, and RNA polymerase III are included in this panel as reflex tests when the ANA IFA result is positive. The presence of any of these 3 autoantibodies is part of the ACR/European League Against Rheumatism (EULAR) classification criteria for SSc [3]. Identification of certain SSc-associated autoantibodies can help distinguish the various types of SSc and the organ(s) likely to be involved, which is important for determining prognosis and optimal treatment [2].

Several other autoantibodies associated with SSc are less prevalent or less recently characterized and thus are not included in this panel (eg, antibodies to U1-snRNP, Th/To, and fibrillarin). Detecting these autoantibodies may also be helpful in the evaluation of SSc [2].

The results of this test should be interpreted in the context of pertinent clinical and family history and physical examination findings.

References
1. Methodology of testing for antinuclear antibodies (position statement). 2009. American College of Rheumatology. Updated December 2019. Accessed May 15, 2023. https://assets.contentstack.io/v3/assets/bltee37abb6b278ab2c/blta48818378bc89445/acr-position-statement-methodology-testing-antinuclear-antibodies.pdf
2. Stochmal A, et al. Clin Rev Allergy Immunol. 2020;58(1):40-51.
3. van den Hoogen F, et al. Arthritis Rheum. 2013;65(11):2737-2747.