Monogenic Systemic Lupus Erythematosus (SLE) in Northern Israel

Background: Systemic Lupus erythematous (SLE) is a heterogenic clinical syndrome with a multifactorial etiology including diverse environmental, immunological and genetic causes and modifiers. Increasingly, utilizing next generation sequencing tooIs, monogenic forms of SLE have been identified. The aim of our study was to identify monogenic causes of SLE in the unique pediatric population of Northern Israel.

Methods: A retrospective and prospective study was carried out between 2010-2021 in a single tertiary pediatric medical center. Genetic testing including Whole exome sequencing (WES) was performed for select patients including family history of SLE, consanguinity and\or clinical findings suggestive of specific disorder.

Results: 76 children were diagnosed with SLE. 12/76 (all females) had one or more relatives with SLE, including a pedigree with 4 affected members. Mean age at presentation was 10.8±4.4. A monogenic disorder was identified in total of 6/76 of pedigrees. Four patients were diagnosed with Prolidase deficiency, one patient with ADAR1 mutation related to Aicardi–Goutières syndrome. Candidate variants in genes related to immune system were identified in one proband and her father requiring further study. Additional WES results are pending.

Conclusions: We detected monogenic causes of SLE in a select cohort of patient in Northern Israel. Identification of a genetic basis for disease has direct clinical implication for patients and families and can also enhance our understanding of the pathogenesis and disease mechanisms involved in the more common sporadic forms of SLE.