ArticleArthritis & rheumatology (Hoboken, N.J.)2017
Brief Report: Deficiency of Complement 1r Subcomponent in Early-Onset Systemic Lupus Erythematosus: The Role of Disease-Modifying Alleles in a Monogenic Disease.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 45 citations in OpenAlex.
- Dysregulation of complement components associated with inflammation and coagulation in virally suppressed people living with HIV.Journal of immunology (Baltimore, Md. : 1950) · 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
- Towards precision medicine for systemic lupus erythematosus and neuropsychiatric manifestations.Expert review of precision medicine and drug development · 2025Article
- Primary immunodeficiency as a cause of immune-mediated kidney diseases.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2024Review
- Monogenic lupus - from gene to targeted therapy.Molecular and cellular pediatrics · 2024Review
- Low C4A copy numbers and higher HERV gene insertion contributes to increased risk of SLE, with absence of association with disease phenotype and disease activity.Immunologic research · 2024Article
- Genetic interrogation for sequence and copy number variants in systemic lupus erythematosus.Frontiers in genetics · 2024Review
- The Relationship between Complement ComponentsGenes · 2023Article
- The complement system and human autoimmune diseases.Journal of autoimmunity · 2023Review
- Vasculitis and vasculopathy associated with inborn errors of immunity: an overview.Frontiers in pediatrics · 2023Review
- Genome-wide DNA methylation pattern in whole blood of patients with Hashimoto thyroiditis.Frontiers in endocrinology · 2023Article
- Childhood-onset systemic lupus erythematosus: characteristics and the prospect of glucocorticoid pulse therapy.Frontiers in immunology · 2023Review
- Non-oral manifestations in adults with a clinical and molecularly confirmed diagnosis of periodontal Ehlers-Danlos syndrome.Frontiers in genetics · 2023Article
- Novel loss-of-function mutations inClinical kidney journal · 2022Article
- Dysregulation of complement factor H in juvenile-onset systemic lupus erythematosus patients.Archives of rheumatology · 2022Article
- The yin and the yang of early classical pathway complement disorders.Clinical and experimental immunology · 2022Review
- Genetic workup as a complementary tool for the diagnosis of primary complement component deficiencies: a multicenter experience.European journal of pediatrics · 2022Article
- Systemic lupus erythematosus as a genetic disease.Clinical immunology (Orlando, Fla.) · 2022Article
- Polygenic autoimmune disease risk alleles impacting B cell tolerance act in concert across shared molecular networks in mouse and in humans.Frontiers in immunology · 2022Review
- Homozygous variant p. Arg90His in NCF1 is associated with early-onset Interferonopathy: a case report.Pediatric rheumatology online journal · 2021Article
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Authors and funding
24 authors at 5 institutions in 3 countries.
Funding
Abstract
objectiveTo identify a genetic cause of early-onset systemic lupus erythematosus (SLE) in a large consanguineous family from Turkey and to study the mechanisms of the disease.
methodsWe performed whole-exome sequencing and single-nucleotide polymorphism array genotyping in family members with and without SLE. Protein and gene expression, cytokine profile, neutrophil extracellular trap (NET) formation, and presence of low-density granulocytes were evaluated in patient primary cells and serum samples.
resultsWe identified a novel, homozygous, loss-of-function mutation (p.Pro445Leufs*11) in the C1R gene. Using the Sanger method of DNA sequencing in 14 family members, we confirmed the presence of the mutation in 4 patients with SLE and in an asymptomatic 9-year-old girl. Complement levels were low in sera from patients with truncated C1r protein. Two siblings with SLE who were available for detailed evaluation exhibited strong type I interferon (IFN) inflammatory signatures despite their disease being clinically inactive at the time of sampling. The type I IFN transcriptional signature in the patients' blood correlated with disease expressivity, whereas the neutrophil signature in peripheral blood mononuclear cells was likely associated with disease severity. The female patient with SLE with the most severe phenotype presented with a stronger neutrophil signature, defined by enhanced NET formation and the presence of low-density granulocytes. Analysis of exome data for modifying alleles suggested enrichment of common SLE-associated variants in the more severely affected patients. Lupus-associated HLA alleles or HLA haplotypes were not shared among the 4 affected subjects.
conclusionOur findings revealed a novel high-penetrance mutation in C1R as the cause of monogenic SLE. Disease expressivity in this family appears to be influenced by additional common and rare genetic variants.
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