ArticleArthritis & rheumatology (Hoboken, N.J.)2022
Strong Association of Combined Genetic Deficiencies in the Classical Complement Pathway With Risk of Systemic Lupus Erythematosus and Primary Sjögren's Syndrome.
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 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 30 citations in OpenAlex.
- Novel HLA class I and II insights into the pathogenesis of systemic sclerosis-associated interstitial lung disease.Annals of the rheumatic diseases · 2026Article
- The Intertwining Between Arthritis and Inborn Errors of Immunity.Journal of clinical medicine · 2026Review
- Overrepresentation of Germline Immune-Related Gene Variants in Patients with Acquired Bone Marrow Failure.Journal of clinical immunology · 2025Article
- Dysregulation of complement components associated with inflammation and coagulation in virally suppressed people living with HIV.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Plasma C4d levels correlate with treatment response and renal activity in proliferative lupus nephritis.Rheumatology (Oxford, England) · 2025Article
- Computational Insights into the Polypharmacological Landscape of BCR-ABL Inhibitors: Emphasis on Imatinib and Nilotinib.Pharmaceuticals (Basel, Switzerland) · 2025Article
- scPrediXcan integrates deep learning methods and single-cell data into a cell-type-specific transcriptome-wide association study framework.Cell genomics · 2025Article
- scPrediXcan integrates advances in deep learning and single-cell data into a powerful cell-type-specific transcriptome-wide association study framework.bioRxiv : the preprint server for biology · 2025Article
- [Analysis of characteristics related to the disease activity of systemic lupus erythematosus and construction of an evaluation model].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2024Article
- Yao syndrome in a child with C2 deficiency.The journal of allergy and clinical immunology. In practice · 2024Article
- 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
- Article
- CXCL9 may serve as a potential biomarker for primary Sjögren's syndrome with extra-glandular manifestations.Arthritis research & therapy · 2024Article
- Comprehensive analysis of IRF8-related genes and immune characteristics in lupus nephritis.Frontiers in pharmacology · 2024Article
- Article
- Observations for Sjögren's Pigment Epithelial Reticular Dystrophy in a 16-Year-Old Boy-An Extremely Rare Retinal Case Report.Journal of clinical medicine · 2023Article
- Sex-specific differences in primary Sjögren's disease.Frontiers in dental medicine · 2023Review
- Nomogram Based on Inflammatory Factor to Predict Therapeutic Response of Thrombocytopenia in Patients with Primary Sjögren's Syndrome.Journal of inflammation research · 2023Article
- Overview on the Link Between the Complement System and Auto-Immune Articular and Pulmonary Disease.Open access rheumatology : research and reviews · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
34 authors at 15 institutions in 3 countries.
Funding
Abstract
objectiveComplete genetic deficiency of the complement component C2 is a strong risk factor for monogenic systemic lupus erythematosus (SLE), but whether heterozygous C2 deficiency adds to the risk of SLE or primary Sjögren's syndrome (SS) has not been studied systematically. This study was undertaken to investigate potential associations of heterozygous C2 deficiency and C4 copy number variation with clinical manifestations in patients with SLE and patients with primary SS.
methodsThe presence of the common 28-bp C2 deletion rs9332736 and C4 copy number variation was examined in Scandinavian patients who had received a diagnosis of SLE (n = 958) or primary SS (n = 911) and in 2,262 healthy controls through the use of DNA sequencing. The concentration of complement proteins in plasma and classical complement function were analyzed in a subgroup of SLE patients.
resultsHeterozygous C2 deficiency-when present in combination with a low C4A copy number-substantially increased the risk of SLE (odds ratio [OR] 10.2 [95% confidence interval (95% CI) 3.5-37.0]) and the risk of primary SS (OR 13.0 [95% CI 4.5-48.4]) when compared to individuals with 2 C4A copies and normal C2. For patients heterozygous for rs9332736 with 1 C4A copy, the median age at diagnosis was 7 years earlier in patients with SLE and 12 years earlier in patients with primary SS when compared to patients with normal C2. Reduced C2 levels in plasma (P = 2 × 10
conclusionWe demonstrate that a genetic pattern involving partial deficiencies of C2 and C4A in the classical complement pathway is a strong risk factor for SLE and for primary SS. Our results emphasize the central role of the complement system in the pathogenesis of both SLE and primary SS.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.