PO:02:053 Autoantibody clusters and SIGLEC1 are predictive of systemic lupus erythematosus development

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Objectives Up to one third of patients with suspected systemic lupus erythematosus (SLE) progress to definite disease, but reliable predictive markers are lacking. We previously developed a Lupus Lymphocyte Activation Score (LLAS) based on five immune cell subsets (transitional B cells, age-associated B cells, plasmablasts, Tph, and Tfh cells) associated with SLE development (Horisberger, 2024). Here, we examined the relationship between autoantibody profiles, including anti-dense fine speckled 70 (DFS70) antibodies, blood sialic acid binding Ig-like lectin 1 (SIGLEC1, a monocyte type I interferon biomarker), LLAS, and SLE, and other autoimmune rheumatic disease (SARD) progression among individuals with suspected SLE.Methods Blood samples were collected from 45 patients with new-onset (<5 years) suspected SLE and ANA positivity at the Brigham and Women’s Hospital Lupus Center. At baseline, none met classification criteria for SLE or other SARDs. All received prednisone <10 mg/day and no immunosuppressants. Soluble SIGLEC1 was measured by ELISA, and a comprehensive autoantibody profile was performed: ANA by indirect immunofluorescence on HEp-2 cells (patterns classified per ICAP AC nomenclature), SLE-related autoantibodies (including anti-DFS70) by a fully automated particle-based multi-analyte platform, and anti-C1q and antiphospholipid antibodies by ELISA. Hierarchical clustering defined autoantibody patterns, which were related to disease progression, LLAS (sum of standardized proportions of the five lymphocyte subsets), and SIGLEC1 levels.Results Of 45 patients, 36 had longitudinal follow-up (mean = 13.6 months). Three progressed to classified SLE (2012 SLICC or 2019 EULAR/ACR), and four developed dermatomyositis or Sjögren disease. Five autoantibody clusters were identified ( figure 1A). Cluster A (AC-4 nuclear speckled with multiple autoantibodies: anti-RNP, -dsDNA, -Ro60/SSA) was more likely to develop SLE or another connective tissue disease (OR 1.94, 95% CI 0.42–3.46) than other clusters, particularly Cluster C (no autoantibodies) (figure 1B). Cluster A also showed significantly higher SIGLEC1 levels than Cluster E (figure 1C). LLAS did not differ by cluster (figure 1D).Abstract PO:02:053 Figure 1Conclusions A nuclear speckled autoantibody profile with multiple reactivities (anti-RNP, -dsDNA, -Ro60/SSA) was associated with higher SIGLEC1 and greater risk of SARD progression. Ongoing analyses will assess whether combining LLAS, SIGLEC1, and autoantibody signatures improves early prediction of SLE and other SARD development.

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