title: A study of the major histocompatibility complex in a Caucasian family with multiple cases of systemic lupus erythematosus: association with the C4AQ0 phenotype.
abstract: OBJECTIVE
  In an epidemiological survey of systemic lupus erythematosus (SLE) in Iceland several families with multiple cases were identified. In one family, 35 individuals (family members and spouses) in 3 generations were studied clinically, tested for autoantibody formation, and typed for HLA and toxicity complement phenotypes.
  
  
  METHODS
  Typing for HLA-A, B, C, DR, and DQ was performed by microlymphocytotoxic assay. In selected samples HLA-DR typing by polymerase chain reaction amplification with sequence specific primers was performed. C4 allotypes were defined by agarose gel protein electrophoresis followed by immunofixation with goat antisera.
  
  
  RESULTS
  Five family members fulfilled 4 or more criteria for SLE. Additionally, 5 family members had clinical manifestations or positive serology but did not fulfill 4 ARA criteria. The mean age at onset of symptoms was 22 yrs (8-40). Other autoimmune diseases were not documented in family members. C4A null seemed to be highly associated with disease in this family. All except one patient with SLE and all those with clinical manifestations and positive serology had C4A null in the homozygous or heterozygous form. The individual with SLE and not carrying C4A null had both HLA haplotypes identical. It is noteworthy that there were 5 different C4A null bearing haplotypes involved, of which 3 originated from the spouses.
  
  
  CONCLUSIONS
  Our results are consistent with the argument that C4A deficiency plays a role in the pathogenesis of SLE. There is, however, the possibility of an unidentified environmental or another genetic factor being involved.
authors.affiliation: Department of Internal Medicine, University Hospital, Reykjavík, Iceland.
authors.forename: K
authors.initials: K
authors.lastname: Steinsson
authors.forename: A
authors.initials: A
authors.lastname: Arnason
authors.forename: K
authors.initials: K
authors.lastname: Erlendsson
authors.forename: R
authors.initials: R
authors.lastname: Fossdal
authors.forename: I
authors.initials: I
authors.lastname: Skaftadóttir
authors.forename: S
authors.initials: S
authors.lastname: Jónsdóttir
authors.forename: M
authors.initials: M
authors.lastname: Fjalarson
authors.forename: J
authors.initials: J
authors.lastname: Thorsteinsson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003181:Complement C4 / Q000235:genetics*; D005260:Female; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000208:ethnology* / Q000235:genetics*; D008285:Major Histocompatibility Complex; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D044465:White People
chemical_list: D003181:Complement C4