ArticleRheumatology (Oxford, England)2023
Panel sequencing links rare, likely damaging gene variants with distinct clinical phenotypes and outcomes in juvenile-onset SLE.
Article in Rheumatology (Oxford, England), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- Development of CARRA/PReS-endorsed consensus Core and Expanded Datasets in childhood-onset systemic lupus erythematosus for international registry-based research.Annals of the rheumatic diseases · 2025Guideline
- How loss-of-function mutations inJournal of translational autoimmunity · 2026Review
- A symposium update on the key perspectives in systemic sclerosis and systemic lupus erythematosus.Journal of translational autoimmunity · 2026Review
- Monogenic lupus with SLC7A7 mutations: a retrospective study from a Chinese center.Orphanet journal of rare diseases · 2026Article
- Insights into the pathogenesis of childhood-onset SLE in the past decade.Nature reviews. Rheumatology · 2026Review
- Juvenile-onset Systemic Lupus Erythematosus: Recent Advances in Pathogenesis and Treatment.Current rheumatology reports · 2025Review
- Genetic Susceptibility in Sinusoidal Obstruction Syndrome/Veno-Occlusive Disease: A Case-Control Study.International journal of molecular sciences · 2025Article
- Next generation sequencing analysis reveals complex genetic architecture of childhood-onset systemic lupus erythematosus.Lupus science & medicine · 2025Article
- Across ancestries, HLA-B∗08:01∼DRB1∗03:01 (DR3) and HLA-DQA∗01:02 (DR2) increase the risk to develop juvenile-onset systemic lupus erythematosus through low complement C4 levels.Journal of translational autoimmunity · 2025Article
- Genetic and epigenetic factors shape phenotypes and outcomes in systemic lupus erythematosus - focus on juvenile-onset systemic lupus erythematosus.Current opinion in rheumatology · 2025Review
- How (Ultra-)Rare Gene Variants Improve Our Understanding of More Common Autoimmune and Inflammatory Diseases.ACR open rheumatology · 2025Review
- Towards precision medicine for systemic lupus erythematosus and neuropsychiatric manifestations.Expert review of precision medicine and drug development · 2025Article
- Profile of juvenile systemic lupus erythematosus patients with a special reference to monogenic lupus and lupus nephritis: a cross-sectional study.Rheumatology international · 2024Article
- Childhood-Onset Systemic Lupus Erythematosus (cSLE): An International Perspective.Current allergy and asthma reports · 2024Review
- Systemic lupus erythematosus genetics: insights into pathogenesis and implications for therapy.Nature reviews. Rheumatology · 2024Review
- Noonan syndrome and Noonan-like syndrome with loose anagen hair: rare phenotypes may emerge during follow-up.Translational pediatrics · 2024Article
- Mendelian Causes of Autoimmunity: the Lupus Phenotype.Journal of clinical immunology · 2024Review
- Lupus Nephritis Biomarkers: A Critical Review.International journal of molecular sciences · 2024Review
- Genetic interrogation for sequence and copy number variants in systemic lupus erythematosus.Frontiers in genetics · 2024Review
- Case Report: p40Frontiers in pediatrics · 2024Article
Corrections and comments
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Authors and funding
26 authors at 20 institutions in 5 countries.
Funding
Abstract
objectivesJuvenile-onset systemic lupus erythematosus (jSLE) affects 15-20% of lupus patients. Clinical heterogeneity between racial groups, age groups and individual patients suggests variable pathophysiology. This study aimed to identify highly penetrant damaging mutations in genes associated with SLE/SLE-like disease in a large national cohort (UK JSLE Cohort Study) and compare demographic, clinical and laboratory features in patient sub-cohorts with 'genetic' SLE vs remaining SLE patients.
methodsBased on a sequencing panel designed in 2018, target enrichment and next-generation sequencing were performed in 348 patients to identify damaging gene variants. Findings were integrated with demographic, clinical and treatment related datasets.
resultsDamaging gene variants were identified in ∼3.5% of jSLE patients. When compared with the remaining cohort, 'genetic' SLE affected younger children and more Black African/Caribbean patients. 'Genetic' SLE patients exhibited less organ involvement and damage, and neuropsychiatric involvement developed over time. Less aggressive first line treatment was chosen in 'genetic' SLE patients, but more second and third line agents were used. 'Genetic' SLE associated with anti-dsDNA antibody positivity at diagnosis and reduced ANA, anti-LA and anti-Sm antibody positivity at last visit.
conclusionApproximately 3.5% of jSLE patients present damaging gene variants associated with younger age at onset, and distinct clinical features. As less commonly observed after treatment induction, in 'genetic' SLE, autoantibody positivity may be the result of tissue damage and explain reduced immune complex-mediated renal and haematological involvement. Routine sequencing could allow for patient stratification, risk assessment and target-directed treatment, thereby increasing efficacy and reducing toxicity.
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