Finding lupus in the ANA haystack

Abstract

Diagnosis of SLE in early stages is challenging due to the heterogeneous nature of presenting symptoms and the poor performance metrics of the screening ANA test. Even the more specific double-stranded DNA autoantibody has relatively low predictive value in early disease. A consequence is delayed referral, with the likelihood that some patients have progression of disease prior to specialist evaluation. Tests that might fill this diagnostic gap are therefore needed. The AVISE Connective Tissue Disease Test that uses a multiplex approach to detect autoantibodies and cell-bound complement products has shown utility in distinguishing SLE from other rheumatological conditions. Whether it might be useful in early disease stages to predict progression is addressed in a recent study by Liang and colleagues, who tested clinic patients who had non-specific findings with the objective of determining whether AVISE could predict onset of SLE. While this test provided more useful prognostic information than other available diagnostics, it had relatively low sensitivity, suggesting that significant numbers of patients with preclinical SLE would be missed by this screening. The need remains for development of diagnostics with robust sensitivity and specificity in early disease that would also deliver prognostic information about risk for SLE. Such tests would have great value as a tool for primary providers to more efficiently triage ANA-positive patients for appropriate specialty evaluation.

Phenotype Risk Score but Not Genetic Risk Score Aids in Identifying Individuals With Systemic Lupus Erythematosus in the Electronic Health Record

“…Identifying individuals with autoimmune diseases, including SLE, can be challenging due to SLE disease heterogeneity. Individuals with SLE and other autoimmune diseases face significant diagnostic delays (5,6,36). While SLE risk models have been developed to identify individuals with SLE, these models have not been validated, deployed in real time in the EHR, or assessed to determine if they improve outcomes (4,37).…”

“…One study demonstrated that it took on average 7 years from symptom onset for SLE diagnosis (4). Delays in diagnosis lead to delays in treatment that result in increased SLE disease damage and associated increased morbidity and mortality (5,6).…”

Identifying antinuclear antibody positive individuals at risk for developing systemic autoimmune disease: development and validation of a real-time risk model

“…Studies have shown that risk models that include race could potentially disadvantage high-risk groups from receiving appropriate care ( 28 , 29 ). We performed a sensitivity analysis where race was included in the model, as studies demonstrate an increased risk of developing autoimmune disease in racial and ethnic underserved populations ( 1 , 5 ).…”

Emerging Molecular Markers Towards Potential Diagnostic Panels for Lupus

“…ANA has a long history serving as a classical clinical marker for the detection and screening of autoantibodies in autoimmune diseases including SLE, however, the sensitivity as well as accuracy of the ANA tests in diagnosis is not satisfactory due to false positives and negatives in previous reports (92)(93)(94)(95). Therefore, standardization of ANA-based diagnostic tests in autoimmune diseases are highly recommended (92,96), including the integration of immunofluorescence ANA (IFA) test with solid phase assays (SPA) such as bead-based highthroughput and/or multiplexing assays (92,96).…”