TY - JOUR
T1 - 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
AU - Ross, Ian
AU - Boulle, Andrew
AU - Soule, Steven
AU - Levitt, Naomi
AU - Pirie, Fraser
AU - Karlsson, Anders
AU - Mienie, Japie
AU - Yang, Ping
AU - Wang, Hongjie
AU - She, Jin-Xiong
AU - Winter, William
AU - Schatz, Desmond
PY - 2010/9
Y1 - 2010/9
N2 - 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. Design We compiled a national registry of patients from primary care, referral centres and private practices. Patients 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.
AB - 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. Design We compiled a national registry of patients from primary care, referral centres and private practices. Patients 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.
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U2 - 10.1111/j.1365-2265.2010.03807.x
DO - 10.1111/j.1365-2265.2010.03807.x
M3 - Article
C2 - 20455895
AN - SCOPUS:77955719285
SN - 0300-0664
VL - 73
SP - 291
EP - 298
JO - Clinical Endocrinology
JF - Clinical Endocrinology
IS - 3
ER -