Background: Systemic lupus erythematosus (SLE) is a highly heterogeneous disease caused by aberrant activation of the immune system and may present with multi-system organ involvement. Systems biology and bioinformatics approaches have provided critical insights into SLE pathogenesis, revealing dysregulated pathways, potential biomarkers and therapeutic targets [1]. However, translating these results into equitable clinical practice requires transparent and representative baseline data that reflects the diversity of the studied population. Sex and ethnicity are not merely descriptive, as they are biologically relevant and that influence gene expression patterns and disease progression, as well as response to therapy [2]. As well, disease outcomes are also affected by health disparities, as patients in lower socioeconomic status report worse outcomes and higher disease activity [3, 4]. Thus, the applicability of these findings may be hindered by both geographical limitations and lack of transparency. To address this gap, we systematically assessed SLE transcriptomic datasets deposited in publicly available repositories, analyzing the representation of sex, ethnicity and national income.

Objectives: To assess the consistency of baseline demographic variables across datasets deposited in public repositories and the representativity of low- and middle-income countries (LMICs) in SLE transcriptomic studies.

Methods: We systematically searched the Gene Expression Omnibus (GEO) using terms including “SLE”, “RNA-seq”, “microarray”, and tissue-specific keywords (“blood”, “PBMC”, “skin”, “kidney”). Duplicates, pediatric studies, animal models, and non-SLE datasets were excluded. From linked publications, we extracted: publication year, World Bank region and classification, analyzed patients, sex, and ethnicity. Missing data was labeled as non-identifiable (NI). Descriptive statistics were used.

Results: Of 101 identified datasets, 51 were included in the analysis (publication range: 2005–2024). Most originated from North America (n=29) and Europe & Central Asia (n=14), followed by East Asia & Pacific (n=6). Only one dataset originated from Latin American & Caribbean and one from Middle East, North Africa, Afghanistan & Pakistan. Not a single dataset originated from low- or lower-middle income countries. Only 2 datasets origin from upper-middle-income countries, while 49 were conducted in high-income countries (HICs). In total, 2475 patient samples were analyzed: 76% were women (n=1894), and 9% were men (n=224). However, 15% of patients were NI. On the other hand, ethnicity was not reported in 70% of datasets (n=1,018 patients). Among those reported, 50% (n=750) of patients were reported as white, 22% as black (n=321), 11% as Hispanic/Latino (n=164), and 1% as Asian (n=15). 2% were classified as Turkish (n=38), and barely 0.1% as Arab (n=11).

Conclusions: This is the first systematic search conducted in a public repository of transcriptomic profiles of patients with SLE, which highlights the virtual absence of LMICs, even though sociodemographic variables impact patient outcomes in rheumatic diseases. Combined with the lack of transparency when reporting sex and ethnic background as demographic variables, these issues hinder the applicability of translating basic results into clinical practice for patients. This study underscores the need for a standardized reporting guideline in transcriptomic studies. Furthermore, efforts should be assessed at bridging the gap between LMICs and HICs to attain a holistic view on SLE pathogenesis.

REFERENCES: [1] Kim, Ki-Jo et al. “Applications of systems approaches in the study of rheumatic diseases.” The Korean journal of internal medicine vol. 30,2 (2015): 148-60. doi:10.3904/kjim.2015.30.2.148.

[2] Chae, David H et al. “Racial Discrimination, Disease Activity, and Organ Damage: The Black Women’s Experiences Living With Lupus (BeWELL) Study.” American journal of epidemiology vol. 188,8 (2019): 1434-1443. doi:10.1093/aje/kwz105.

[3] Yelin, Edward et al. “Poverty, Neighborhoods, Persistent Stress, and Systemic Lupus Erythematosus Outcomes: A Qualitative Study of the Patients’ Perspective.” Arthritis care & research vol. 71,3 (2019): 398-405. doi:10.1002/acr.23599.

[4] Kaplowitz, Elianna T et al. “Contribution of Socioeconomic Status to Racial/Ethnic Disparities in Adverse Pregnancy Outcomes Among Women With Systemic Lupus Erythematosus.” Arthritis care & research vol. 70,2 (2018): 230-235. doi:10.1002/acr.23263.

Acknowledgments: NIL.

Disclosure of Interests: None declared.