Systemic lupus erythematosus (SLE) is an autoimmune connective tissue disease with a heterogeneous clinical presentation that can affect skin, joints, serosal surfaces, kidneys, nervous system and other organs. Diagnosis typically depends on integrating clinical features with individual serologic tests such as antinuclear antibody (ANA), anti‑double stranded DNA (anti‑dsDNA), and anti‑Smith (anti‑Sm), and with formal classification criteria (for example, EULAR/ACR 2019, SLICC 2012, and ACR criteria) that use combinations of clinical and immunologic findings to assign likelihood of SLE (entry ANA requirement and weighted criteria in the EULAR/ACR system).
Commercially available multianalyte serum biomarker panels (examples include Avise® Lupus / Avise® CTD / AVISE® SLE Monitor and SLE‑Key®) combine multiple autoantibodies and cell‑bound complement activation products (CB‑CAPs) and report results using tiered testing algorithms and proprietary index or risk scores. For example, the Avise® approach uses a tier 1 screen (anti‑Sm, EC4d, BC4d, anti‑dsDNA) with specified positivity cutoffs (e.g., anti‑Sm >10 U/mL; EC4d >75 U/mL; BC4d >200 U/mL; anti‑dsDNA >301 U/mL with Crithidia confirmation) and, when tier 1 is negative, a tier 2 index score calculated from ANA, CB‑CAP measures and additional autoantibodies (index range −5 to 5; −0.1 to 0.1 indeterminate). The SLE‑Key® test reports an algorithmic IgG/IgM risk score across a broader set of biomarkers.
The evidence base evaluating these multianalyte panels is limited. Published data are predominantly observational and retrospective, frequently industry‑sponsored, and many studies evaluated patients with established SLE rather than the intended use population of patients with new or undifferentiated symptoms. Diagnostic accuracy studies report moderate sensitivity and relatively high specificity when distinguishing established SLE from other rheumatic diseases (combined tier 1/tier 2 specificity ~86%; some analyses of combinations report ~87%), but these performance estimates may be inflated by study populations that already met classification criteria.
Prospective data are sparse. One randomized trial (CARE for Lupus) examined the impact of Avise® testing on rheumatologists' estimated likelihood of SLE versus standard laboratory testing and found a greater change in physician likelihood after Avise® testing at 12 weeks, but the trial had short follow‑up (12 weeks), a non‑standardized comparator, no blinding, and did not demonstrate patient‑centered health outcome improvements. Other prospective cohort studies have suggested an association between positive multianalyte scores and later fulfillment of classification criteria, but sample sizes were small and follow‑up limited.