Low C4, C4A and C4B Gene Copy Numbers Are Stronger Risk Factors for Juvenile-Onset Than for Adult-Onset Systemic Lupus Erythematosus

Rheumatology (Oxford). 2016 May;55(5):869-73. doi: 10.1093/rheumatology/kev436. Epub 2016 Jan 22.

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).

Conclusion: 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.

Keywords: Complement system; gene copy number; immunogenetics; juvenile SLE; pediatric rheumatology; systemic lupus erythematosus.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Age of Onset
  • Aged
  • Case-Control Studies
  • Complement C4 / deficiency
  • Complement C4 / genetics*
  • Complement C4a / genetics
  • Complement C4b / genetics
  • Female
  • Gene Dosage*
  • Genetic Predisposition to Disease
  • Humans
  • Lupus Erythematosus, Systemic / complications
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology
  • Male
  • Middle Aged
  • Pericarditis / etiology
  • Pericarditis / genetics
  • Pericarditis / immunology
  • Risk Factors
  • Young Adult

Substances

  • Complement C4
  • Complement C4a
  • Complement C4b