Citations 1
Development and Temporal Validation of AI ‐Enhanced Human Epithelial Type 2 Indirect Immunofluorescence Image Analysis for Specific Autoantibody Prediction in Systemic Autoimmune Rheumatic Diseases
Vanderboom, Patrick, Dasari, Surendra, Sandino-Bermúdez, Marlon J , Tebo, Anne E. , Snyder, Melissa, Duarte‐García, Alí
Arthritis & Rheumatology | August 28, 2026 | Volume: No volume available | Issue: No issue available | Pages: No page available
Objective Antinuclear antibody (ANA) indirect immunofluorescence (IIF) is the reference standard but depends on subjective pattern interpretation. We tested whether artificial intelligence (AI) applied to ANA IIF images could identify specific autoantibodies. Methods We assembled a cohort of ANA‐positive patients (human epithelial type 2 IIF titer ≥1:80) with anti–double‐stranded DNA (dsDNA), anti‐Smith (Sm) antibody, ribonucleoprotein (RNP), anti‐Sjögren's disease‐related antigen A (SSA), anti‐Sjögren's disease‐related antigen B (SSB), anti‐topoisomerase I (Scl‐70), or centromere antibody (CMA) testing within 90 days. The development cohort (December 12, 2016–December 31, 2022) included the first ANA test per patient. Two AI architectures were trained for each autoantibody. Performance was assessed using area under the receiver operating characteristic curve (AUROC), sensitivity, specificity, and accuracy; comparisons with IIF patterns were summarized as pattern‐antibody agreement. A prospective cohort (January 1, 2023–August 20, 2024), including a dsDNA assay transition, provided temporal validation. Results Among 512,959 patients, 47,890 met inclusion criteria (mean age 55 [SD 17.6], 78% female). Models for CMA, dsDNA, Sm, SSA, and SSB achieved AUROC ≥0.80 (CMA highest: AUROC 0.95, accuracy 94.2%, specificity 95.3%). Compared with associated IIF patterns, dsDNA and Sm models more often classified antibody‐negative cases as negative (dsDNA 88.2% vs 54.7%; Sm 82.6% vs 60.3%) while similarly classifying antibody‐positive cases. Performance for RNP (AUROC 0.68) and Scl‐70 (AUROC 0.59) was lower. In the prospective cohort (n = 21,427), performance was similar; dsDNA discrimination remained stable across assays (AUROC ~0.85). Conclusion AI applied to ANA IIF images identified specific autoantibodies and often improved classification of antibody‐negative cases versus simplified pattern‐based comparators. These findings support its potential to standardize ANA interpretation and triage or reduce confirmatory testing. image