title: Early Complement Component Deficiency in a Single-Centre Cohort of Pediatric Onset Lupus.
abstract: OBJECTIVE
  To assess complement levels C1q, C2, C3 and C4 in children with pediatric-onset lupus during the quiescent stage of disease.
  
  
  METHODS
  Thirty-four consecutive children with pediatric-onset SLE (onset below 12 years), in the quiescent stage were enrolled for the study. Twenty-nine age and sex matched healthy children were also enrolled for the purpose of comparison. Complement C1q and C2 levels were estimated by enzyme-linked immunosorbent assay (ELISA) whereas C3 and C4 were measured by end-point nephelometry. Genetic mutation analysis and functional assessment of classical complement pathway by ELISA were carried out in children with depressed levels of these complements. The study protocol was approved by the Institute Thesis Committee and the Institute Ethics Committee.
  
  
  RESULTS
  Mean complement C1q, C2, C3 and C4 levels were 50.32, 17.28, 1320 and 236 mg/L respectively. Levels of complements were low in 7/34 children with SLE. An early age at onset, low anti-dsDNA titres and predominant skin manifestations were noted in children with decreased levels of complement C1q. Mutation analysis of C1qA gene revealed a homozygous nonsense mutation: C1QA (NM_015991) c.622C>T, p.Q208X in one child. A homozygous acceptor splice site mutation at the -2 position of intron2 of C1QA (c.164-2A>C) was detected in another child. The age at onset of disease was early in both these children, at 2.5 and 1.5 years respectively.
  
  
  CONCLUSIONS
  Children with inherited deficiency of C1q and other early complement components present with early onset lupus that has a distinct clinical and immunological profile.
authors.affiliation: Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
authors.forename: Sagar
authors.initials: S
authors.lastname: Bhattad
authors.affiliation: Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. rawatamit@yahoo.com.
authors.forename: Amit
authors.initials: A
authors.lastname: Rawat
authors.affiliation: Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
authors.forename: Anju
authors.initials: A
authors.lastname: Gupta
authors.affiliation: Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
authors.forename: Deepti
authors.initials: D
authors.lastname: Suri
authors.affiliation: Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
authors.forename: Ravinder
authors.initials: R
authors.lastname: Garg
authors.affiliation: Blood Cell Research, Sanquin Blood Supply Foundation, Amsterdam, The Netherlands.
authors.forename: Martin
authors.initials: M
authors.lastname: de Boer
authors.affiliation: Blood Cell Research, Sanquin Blood Supply Foundation, Amsterdam, The Netherlands.
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
authors.affiliation: Pediatric Allergy and Immunology Unit, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.
authors.forename: Surjit
authors.initials: S
authors.lastname: Singh
mesh_terms: D000293:Adolescent; D000328:Adult; D058070:Asymptomatic Diseases; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003165:Complement System Proteins / Q000235:genetics / Q000378:metabolism*; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000235:genetics / Q000276:immunology*; D008297:Male; D009154:Mutation / Q000235:genetics; D011110:Polymorphism, Genetic; D055815:Young Adult
chemical_list: D003165:Complement System Proteins
keywords: C1q; Pediatric; complement deficiency; lupus; mutation