ArticleArthritis & rheumatology (Hoboken, N.J.)2022
Complement C4 Copy Number Variation is Linked to SSA/Ro and SSB/La Autoantibodies in Systemic Inflammatory Autoimmune Diseases.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Genetic Architecture of Idiopathic Inflammatory Myopathies From Meta-Analyses.Arthritis & rheumatology (Hoboken, N.J.) · 2025Pooled it
- Methylation and polygenic risk scores capture different features of Systemic Lupus Erythematosus.Rheumatology (Oxford, England) · 2026Article
- Distinct Effects of Complement C4A and C4B Copy Numbers in Systemic Sclerosis Serological and Clinical Subtypes.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Integrating genomic structural equation modeling and experimental validation to unravel the genetic basis of male genital lichen sclerosus.Frontiers in immunology · 2026Article
- Identification of Sjögren's disease-associated T cell receptor motifs through deep sequencing.JCI insight · 2025Article
- HLA loci heterozygosity modulates genetic risk in idiopathic inflammatory myopathies.Annals of the rheumatic diseases · 2025Article
- Plasma C4d levels correlate with treatment response and renal activity in proliferative lupus nephritis.Rheumatology (Oxford, England) · 2025Article
- Cross-Population Analysis of Sjögren's Syndrome Polygenic Risk Scores and Disease Prevalence: A Pilot Study.Genes · 2025Article
- Systemic lupus erythematosus genetics: insights into pathogenesis and implications for therapy.Nature reviews. Rheumatology · 2024Review
- Unique Interplay Between Antinuclear Antibodies and Nuclear Molecules in the Pathogenesis of Systemic Lupus Erythematosus.Arthritis & rheumatology (Hoboken, N.J.) · 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
- [Comparison of clinical and immunological characteristics between primary Sjögren's syndrome patients with positive and negative anti-SSB antibody].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2023Article
- Article
- Genetic Characterization of Blood Group Antigens for Polynesian Heritage Norfolk Island Residents.Genes · 2023Article
- The complement system and human autoimmune diseases.Journal of autoimmunity · 2023Review
- Complement as a Biomarker for Systemic Lupus Erythematosus.Biomolecules · 2023Review
- Low copy numbers of complementAnnals of the rheumatic diseases · 2023Article
- Strong Association of Combined Genetic Deficiencies in the Classical Complement Pathway With Risk of Systemic Lupus Erythematosus and Primary Sjögren's Syndrome.Arthritis & rheumatology (Hoboken, N.J.) · 2022Article
- C4A copy number is associated with autoimmune disease.Nature reviews. Rheumatology · 2022Article
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Authors and funding
42 authors at 15 institutions in 4 countries.
Funding
Abstract
objectiveCopy number variation of the C4 complement components, C4A and C4B, has been associated with systemic inflammatory autoimmune diseases. This study was undertaken to investigate whether C4 copy number variation is connected to the autoimmune repertoire in systemic lupus erythematosus (SLE), primary Sjögren's syndrome (SS), or myositis.
methodsUsing targeted DNA sequencing, we determined the copy number and genetic variants of C4 in 2,290 well-characterized Scandinavian patients with SLE, primary SS, or myositis and 1,251 healthy controls.
resultsA prominent relationship was observed between C4A copy number and the presence of SSA/SSB autoantibodies, which was shared between the 3 diseases. The strongest association was detected in patients with autoantibodies against both SSA and SSB and 0 C4A copies when compared to healthy controls (odds ratio [OR] 18.0 [95% confidence interval (95% CI) 10.2-33.3]), whereas a weaker association was seen in patients without SSA/SSB autoantibodies (OR 3.1 [95% CI 1.7-5.5]). The copy number of C4 correlated positively with C4 plasma levels. Further, a common loss-of-function variant in C4A leading to reduced plasma C4 was more prevalent in SLE patients with a low copy number of C4A. Functionally, we showed that absence of C4A reduced the individuals' capacity to deposit C4b on immune complexes.
conclusionWe show that a low C4A copy number is more strongly associated with the autoantibody repertoire than with the clinically defined disease entities. These findings may have implications for understanding the etiopathogenetic mechanisms of systemic inflammatory autoimmune diseases and for patient stratification when taking the genetic profile into account.
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