title: Low C4, C4A and C4B gene copy numbers are stronger risk factors for juvenile-onset than for adult-onset systemic lupus erythematosus.
abstract: OBJECTIVE
  Complete deficiency of Complement C4 component is a strong genetic risk factor for SLE. C4 is encoded by two different genes, C4A and C4B, which show considerable gene copy number (GCN) variation. This study investigates the association of total C4, C4A and C4B GCN with JSLE.
  
  
  METHODS
  Ninety JSLE patients, 170 adult-onset SLE (aSLE) patients and 200 healthy individuals were evaluated for C4A and C4B GCN by quantitative real-time PCR.
  
  
  RESULTS
  JSLE patients had lower GCN for C4A (mean = 1.7; 95% CI: 1.5, 1.9) and C4B (mean = 1.5; 95% CI: 1.3, 1.6) compared with healthy individuals (mean C4A = 2.3; 95% CI: 2.2, 2.5, P < 0.001; C4B = 2.0; 95% CI: 1.8, 2.1; P < 0.001) or with aSLE patients (mean C4A = 1.9; 95% CI: 1.8, 2.1, P = 0.006; mean C4B = 1.8; 95% CI: 1.7, 1.9, P < 0.001). Low total C4 GCN (<4 copies) was more frequent in JSLE than in healthy individuals (59% vs 28%; P < 0.001). The same was observed for low C4A (⩽1 copy) (52% vs 18%; P < 0.001) and for low C4B (60% vs 31%; P < 0.001). JSLE had a stronger association with low total C4 (OR = 3.68, 95% CI: 2.19, 6.20), C4A (OR = 4.98, 95% CI: 2.88, 8.62) and C4B (OR = 3.26; 95% CI: 1.95, 5.47) than aSLE (C4 OR = 2.03; 95% CI: 1.32, 3.13; C4A OR = 2.36; 95% CI: 1.46, 3.81; C4B OR = 1.13; 95% CI: 0.73, 1.74). In addition, pericarditis in JSLE patients was associated with low C4 (OR = 4.13; 95% CI: 1.02, 16.68; P = 0.047) and low C4A (OR = 5.54; 95% CI: 1.37, 22.32; P = 0.016).
  
  
  CONCLUSIONS
  Low total C4, C4A and C4B GCN were associated with a stronger risk for developing JSLE than aSLE. Additionally, low total C4 and C4A GCN are risk factors for pericarditis in JSLE.
authors.affiliation: Rheumatology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo.
authors.forename: Kaline M C
authors.initials: KM
authors.lastname: Pereira
authors.affiliation: Rheumatology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo.
authors.forename: Atila G A
authors.initials: AG
authors.lastname: Faria
authors.affiliation: Children's Hospital and.
authors.forename: Bernadete L
authors.initials: BL
authors.lastname: Liphaus
authors.affiliation: Children's Hospital and.
authors.forename: Adriana A
authors.initials: AA
authors.lastname: Jesus
authors.affiliation: Children's Hospital and Department of Pediatrics, Disciplina de Reumatologia, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: Clovis A
authors.initials: CA
authors.lastname: Silva
authors.affiliation: Children's Hospital and.
authors.forename: Magda
authors.initials: M
authors.lastname: Carneiro-Sampaio
authors.affiliation: Rheumatology Division, Escola Paulista de Medicina, Universidade Federal de São Paulo, luis.andrade@unifesp.br.
authors.forename: Luis E C
authors.initials: LE
authors.lastname: Andrade
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D000368:Aged; D016022:Case-Control Studies; D003181:Complement C4 / Q000172:deficiency / Q000235:genetics*; D015934:Complement C4a / Q000235:genetics; D015935:Complement C4b / Q000235:genetics; D005260:Female; D018628:Gene Dosage; D020022:Genetic Predisposition to Disease; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010493:Pericarditis / Q000209:etiology / Q000235:genetics / Q000276:immunology; D012307:Risk Factors; D055815:Young Adult
chemical_list: D003181:Complement C4; D015934:Complement C4a; D015935:Complement C4b
keywords: Complement system; gene copy number; immunogenetics; juvenile SLE; pediatric rheumatology; systemic lupus erythematosus