1842: Social Vulnerability Index, Type 2 Lupus Symptoms, and Select Dysregulated Immune Features Identify Stage 2 (Pre-classification) SLE in the Lupus Autoimmunity in Relatives (LAUREL) Follow-up Cohort

Background/Purpose: Socioeconomic environmental factors are associated with SLE disease activity and early mortality and may contribute to disease progression in at-risk populations. Blood relatives (BRs) of lupus patients have an increased risk of SLE; identification of those at greatest risk of disease transition is essential for early intervention strategies and prevention trial enrollment. The goal of this study is to determine factors associated with the Social Vulnerability Index (SVI; Flanagan et al. 2011. JHSEM. 8[1]: Article 3) that distinguish previously healthy BRs who progress to SLE compared to those who remain stable.

Methods: We evaluated domains/sub-domains of the census-tract informed SVI in follow-up Pre-SLE (n=54) vs. stable (n=315) BRs of SLE patients with available geographical location data who previously enrolled in a genetics study (mean time to follow-up = 6.3 yrs) and did not meet SLE classification (≥4 ACR criteria) at baseline (BL). ACR classification criteria were determined by medical record review. BRs completed the connective tissue disease questionnaire (CSQ), type 2 symptom questions, and provided demographic and geographic information. Census-tract based percentile rankings of the overall SVI and its domains/subdomains were calculated. BL sample data included serum ANA and SLE-associated autoantibody specificities, as well as 52 plasma immune mediators (xMAP and ELISA assay available for 54 Pre-SLE vs.137 matched stable BRs).

Results: The overall SVI, as well as household composition domain and single parent household, no vehicle, and neighborhood poverty subdomains differentiated Pre-SLE from stable relatives (p< 0.05, Fig. 1A) with increased vulnerability (percentile) in Pre-SLE BRs, even after adjusting for race, age, and ANA positivity (Fig. 1B). Type 2 symptoms, including anxiety, depression, and chronic fatigue, as well as < 7 hours of sleep/night were consistently associated with SVI/domains (p< 0.05; representative features shown in Fig. 2) and specifically affected Pre-SLE vs. stable BRs to varying degree (Fig. 2). In addition to BMI and its associated immune mediator leptin (Spearman r >0.2, p< 0.01), the SLE-CSQ and associated inflammatory factors CRP, BLyS, IL-8/CXCL8, and IL-21 consistently correlated (Spearman r >0.2, p< 0.01) and associated with SVI/domain percentiles/quartiles and specifically affected Pre-SLE vs. stable BRs to varying degree, with IL-8/CXL8 increased with less vulnerability, while other inflammatory and symptomatic factors, including CRP, BLyS, IL-21 and SLE-CSQ scores being increased with greater vulnerability (p< 0.05, representative characteristics shown in Fig. 3).

Conclusion: The SVI was associated with type 2 and inflammatory features, distinguishing BRs at risk of SLE disease transition vs. BRs who remained stable. Addressing aspects of socioeconomic vulnerability, including poverty, single parent households, and access to vehicle transportation, may be required to advance early intervention strategies and prevention trial participation to decrease chronic inflammation and type 2 symptoms associated with SLE in at-risk populations.