title: Autoimmunity predominates in a large South African cohort with Addison's disease of mainly European descent despite long-standing disease and is associated with HLA DQB*0201.
abstract: OBJECTIVE
  We sought to determine whether autoimmunity is the predominant cause of Addison's disease in South Africa and whether human leucocyte antigen (HLA) DQ association exists.
  
  
  METHODS
  We compiled a national registry of patients from primary care, referral centres and private practices.
  
  
  METHODS
  A total of 144 patients, 94 of European descent, 34 Mixed Ancestry, 5 Asian and 11 Black Africans (mean age 45.9 years, range 2.7-88 years; mean duration of disease 13.1 years, range 0-50 years) and controls were matched for gender and ethnicity. All potential causes were investigated.
  
  
  RESULTS
  Fifty one per cent of cases (74 patients) were autoimmune in aetiology. Either 21-hydroxylase autoantibodies (72 patients, 50% of entire patient group) or adrenocortical autoantibodies (35 patients, 24%) were present, while 23% of patients had both. None of the Asian (n = 5) or Black (n = 11) patients had evidence of autoimmune disease. Overall 8% of patients had tuberculosis, 4% adrenoleucodystrophy, 1% adrenocorticotrophic hormone resistance syndrome and 6% X-linked adrenal hypoplasia. In those with autoimmune disease primary hypothyroidism (47%), premature ovarian failure (8%) and type 1 diabetes (7%) were the most prevalent accompanying autoimmune conditions. HLA DQB1*0201 alleles predominated in the autoimmune group (DQB1*0201: 65%vs 43% of controls P = 0.017) with the *0201/*0302 heterozygous genotype being the most prevalent (28%vs 8%P = 0.02).
  
  
  CONCLUSIONS
  While autoimmunity accounts for at least half of patients with Addison's disease in South Africa and is associated with HLA DQB1*0201, none of the Black Africans or Asians in this cohort had adrenal autoantibodies. Moreover, 21-hydroxylase autoantibodies were detectable in a higher proportion than adrenocortical autoantibodies, especially in those patients with a long history after disease onset.
authors.affiliation: Division of Endocrinology, University of Cape Town, Observatory, Cape Town, South Africa. ian.ross@uct.ac.za
authors.forename: Ian
authors.initials: I
authors.lastname: Ross
authors.forename: Andrew
authors.initials: A
authors.lastname: Boulle
authors.forename: Steven
authors.initials: S
authors.lastname: Soule
authors.forename: Naomi
authors.initials: N
authors.lastname: Levitt
authors.forename: Fraser
authors.initials: F
authors.lastname: Pirie
authors.forename: Anders
authors.initials: A
authors.lastname: Karlsson
authors.forename: Japie
authors.initials: J
authors.lastname: Mienie
authors.forename: Ping
authors.initials: P
authors.lastname: Yang
authors.forename: Hongjie
authors.initials: H
authors.lastname: Wang
authors.forename: Jin-Xiong
authors.initials: JX
authors.lastname: She
authors.forename: William
authors.initials: W
authors.lastname: Winter
authors.forename: Desmond
authors.initials: D
authors.lastname: Schatz
mesh_terms: D000224:Addison Disease / Q000097:blood / Q000235:genetics* / Q000276:immunology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People / Q000208:ethnology / Q000235:genetics; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D015551:Autoimmunity / Q000276:immunology*; D044383:Black People / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D013019:South Africa; D044465:White People / Q000208:ethnology / Q000235:genetics; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen