ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1806

Bisphenol a Methylation Scores Associate with SLE and ClinicalSubphenotypes

Holme Vestin1, Nina Oparina2, Maija-Leena Eloranta1, Martina Frodlund3, Iva Gunnarsson4, Christopher Sjowall5, Elisabet Svenungsson6, Lars Rönnblom1, Ann-Christine Syvänen1, Johanna Sandling1, Juliana Imgenberg-Kreuz1 and Dag Leonard1, 1Uppsala university, Uppsala, Sweden, 2UU, Uppsala, Sweden, 3Department of Biomedical and Clinical Sciences, Division of Inflammation and Infection/Rheumatology, Linköping University, Linköping, Sweden, 4Karolinska Institute, Stockholm, Sweden, 5Linköping University, Linköping, Sweden, 6Karolinska Institutet, Stockholm, Sweden

Meeting: ACR Convergence 2024

Keywords: , ,

Session Information

Date: Monday, November 18, 2024

Title: SLE – Etiology & Pathogenesis Poster

Session Type: Poster Session C

Session Time: 10:30AM-12:30PM

Background/Purpose: Systemic Lupus Erythematosus (SLE) is characterized by production of auto-antibodies, immune complex formation and an activated type I interferon system. Both genetic and environmental factors are important in the pathogenesis of the disease. Bisphenol A (BPA) is a widely used chemical with properties similar to estrogen that can be released from polycarbonate plastics and epoxy resins (1). BPA can alter methylation status in humans (2) and recently increased levels of BPA was shown in urine of patients with SLE (3). The effect of BPA on DNA methylation in patients with SLE has not yet been studied. Therefore, the present study aims to investigate if BPA methylation scores are associated with SLE and clinical subphenotypes.

Methods: To construct the BPA scores, CpG sites were selected based on published human BPA exposure studies. CpGs differentially methylated in ≥2 studies and located at independent genetic loci were identified from Illumina HM450k data. Next, twenty of these CpG sites were selected based on BPA methylation effects in cell lines (https://depmap.org/portal). Two BPA scores were developed; the BPAall score including all 20 CpGs and the BPASLE score based on three of the 20 CpGs located at known SLE genetic risk loci. Patients with SLE (fulfilling the ACR-82 criteria) and controls from Sweden were subjected to whole blood DNA Illumina 450k methylation array analysis. The discovery cohort included 347 SLE patients, and 400 blood donor controls. The replication cohort consisted of 201 SLE patients and 187 population controls. Controls were matched for age and sex. Clinical data were collected at time of sampling.

Results: Patients with SLE had a significant lower BPAall score compared with controls in the combined cohort (OR 0.996, p=0.008). Significant lower BPASLE scores were observed in both the discovery cohort (OR 0.739, p< 0.001) and in the replication cohort (OR 0.783, p< 0.001). The BPAall score was associated with arthritis (OR 0.995, p=0.039) and age at diagnosis ≤30 years (OR 0.992, p< 0.001). The BPASLE score was associated with serositis (OR 0.906, p=0.021), prednisolone treatment at sampling (OR 0.797, p< 0.001) and sum of different antinuclear antibodies ≥3 (OR 0.867, p=0.031).

Conclusion: This is the first study to point towards an association between BPA and DNA methylation changes in SLE, suggesting increased BPA-associated DNA methylation changes in these patients.  The BPA scores were also associated with specific subphenotypes including serositis and arthritis. Further studies are needed to clarify the role of BPA in SLE pathogenesis.

References

1.           Ma Y, et al. Environmental Research. 2019

2.           Besaratinia A. Int J Mol Sci. 2023

3.           Wang Y, et al. Ecotoxicology and Environmental Safety. 2024

Disclosures: H. Vestin: None; N. Oparina: None; M. Eloranta: None; M. Frodlund: None; I. Gunnarsson: None; C. Sjowall: Bristol-Myers Squibb(BMS), 3; E. Svenungsson: None; L. Rönnblom: Ampel Biosolutions, 1, AstraZeneca, 1, 6, Bayer, 2, BMS, 1, UCB, 1; A. Syvänen: None; J. Sandling: None; J. Imgenberg-Kreuz: None; D. Leonard: AstraZeneca, 1.

To cite this abstract in AMA style:

Vestin H, Oparina N, Eloranta M, Frodlund M, Gunnarsson I, Sjowall C, Svenungsson E, Rönnblom L, Syvänen A, Sandling J, Imgenberg-Kreuz J, Leonard D. Bisphenol a Methylation Scores Associate with SLE and ClinicalSubphenotypes [abstract]. Arthritis Rheumatol. 2024; 76 (suppl 9). https://acrabstracts.org/abstract/bisphenol-a-methylation-scores-associate-with-sle-and-clinicalsubphenotypes/. Accessed .

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