Background/Purpose: Adverse childhood experiences (ACEs) have been linked to incident childhood-onset SLE (cSLE) and poorer patient-reported outcomes, raising the possibility that early-life stress may contribute to worse cSLE trajectories. This study characterizes ACE exposure in a predominantly African American cSLE cohort and examines its association with physician-assessed and patient-reported outcomes, alongside pilot single-cell transcriptomic data exploring biological pathways related to ACE-related differences.

Methods: Potential participants aged 12–21 years with a rheumatologist-confirmed diagnosis of cSLE and attending a rheumatology clinic visit at a referral center in Louisiana were recruited for this study. Following consent, ACEs were gathered using the Pediatric ACEs and related life events screener (PEARLS), clinical data were obtained through medical record review, and patients completed the PHQ-9 and GAD-7 questionnaires during the same visit. Blood samples were collected from participants, and PBMCs were isolated for downstream single-cell RNA-seq and single-nuclei ATAC-seq. Clinical data are reported for 27 patients, and pilot transcriptomic findings are presented for a subset of 8 patients. Clinical analyses were conducted using GraphPad Prism, and transcriptomic data were analyzed using Python. ACEs were categorized as low (0–1), medium (2–3), and high (≥4).

Results: 24/27 enrolled patients were female and 19 identified as African American. The mean age was 16.1 years (SD ±4.6). The mean SLICC score at diagnosis was 7.4 (SD ±5.35), and the mean SLEDAI at enrollment was 1.77 (SD ±3.0). Median highest lifetime SLEDAI recorded across the cohort was 10 (IQR 8.5). ACEs were reported in 12 of 27 patients, with 7 reporting an ACE score ≥4. No differences in median SLEDAI scores collected at time of ACE evaluation were observed between low, medium and high ACE groups (Fig 1). Patients in low ACE group demonstrated lower peak lifetime SLEDAI compared to the high ACE group (Fig 2) although the association did not reach statistical significance likely due to limited sample size at this early stage of this study. A statistically significant difference between ACEs groups and PHQ-9 scores was found (p< 0.039) (Fig 3), suggesting a link between ACE exposure and depressive symptoms. GO pathway analysis derived from scRNA-seq from eight patients revealed that interferon signaling was most enriched among patients with low ACE exposure, whereas negative regulation of DNA repair was most enriched among those with high ACE exposure.   

Conclusion: In this predominantly African American cohort of adolescents with cSLE, greater depressive symptomatology was observed in those with higher ACE burden. Although there was no difference between disease activity and ACEs at the same visit, a non-statistically significant increase in peak lifetime SLEDAI was observed in high versus low ACE group. Transcriptomic differences between low- and high-ACE groups suggest that psychosocial stress may influence distinct immunologic pathways. Ongoing analyses will assess medication effects, particularly cumulative corticosteroid exposure, as key confounders. 
 

SLEDAI at enrollment visit

Worst lifetime SLEDAI

PHQ9

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/prevalence-and-impact-of-adverse-childhood-experiences-in-pediatric-systemic-lupus-erythematosus/