PMID- 21565792
OWN - NLM
STAT- MEDLINE
DCOM- 20110912
LR  - 20211020
IS  - 1945-7197 (Electronic)
IS  - 0021-972X (Print)
IS  - 0021-972X (Linking)
VI  - 96
IP  - 7
DP  - 2011 Jul
TI  - Dominant suppression of Addison's disease associated with HLA-B15.
PG  - 2154-62
LID - 10.1210/jc.2010-2964 [doi]
AB  - CONTEXT: Autoimmune Addison's disease (AD) is the major cause of primary adrenal 
      failure in developed nations. Autoantibodies to 21-hydroxylase (21OH-AA) are 
      associated with increased risk of progression to AD. Highest genetic risk is 
      associated with the Major Histocompatibility region (MHC), specifically human 
      leukocyte antigen (HLA)-DR3 haplotypes (containing HLA-B8) and HLA-DR4. 
      OBJECTIVE: The objective of the study was the further characterization of AD risk 
      associated with MHC alleles. DESIGN, SETTING, AND PARTICIPANTS: MHC genotypes 
      were determined for HLA-DRB1, DQA1, DQB1, MICA, HLA-B, and HLA-A in 168 total 
      individuals with 21OH-AA (85 with AD at referral and 83 with positive 21OH-AA but 
      without AD at referral). MAIN OUTCOME MEASURE(S): Genotype was evaluated in 
      21OH-AA-positive individuals. Outcomes were compared with general population 
      controls and type 1 diabetes patients. RESULTS: In HLA-DR4+ individuals, HLA-B15 
      was found in only one of 55 (2%) with AD vs. 24 of 63 (40%) 21OH-AA-positive 
      nonprogressors (P = 2 x 10(-7)) and 518 of 1558 (33%) HLA-DR4 patients with type 
      1 diabetes (P = 1 x 10(-8)). On prospective follow-up, none of the 
      HLA-B15-positive, 21-hydroxylase-positive individuals progressed to AD vs. 25% 
      non-HLA-B15 autoantibody-positive individuals by life table analysis (P = 0.03). 
      Single nucleotide polymorphism analysis revealed the HLA-DR/DQ region associated 
      with risk and HLA-B15 were separated by multiple intervening single-nucleotide 
      polymorphism haplotypes. CONCLUSIONS: HLA-B15 is not associated with protection 
      from 21OH-AA formation but is associated with protection from progression to AD 
      in 21OH-AA-positive individuals. To our knowledge, this is one of the most 
      dramatic examples of genetic disease suppression in individuals who already have 
      developed autoantibodies and of novel dominant suppression of an autoimmune 
      disease by a class I HLA allele.
FAU - Baker, Peter R
AU  - Baker PR
AD  - Barbara Davis Center for Childhood Diabetes, University of Colorado Denver, 
      Aurora, Colorado 80045-6511, USA.
FAU - Baschal, Erin E
AU  - Baschal EE
FAU - Fain, Pam R
AU  - Fain PR
FAU - Nanduri, Priyaanka
AU  - Nanduri P
FAU - Triolo, Taylor M
AU  - Triolo TM
FAU - Siebert, Janet C
AU  - Siebert JC
FAU - Armstrong, Taylor K
AU  - Armstrong TK
FAU - Babu, Sunanda R
AU  - Babu SR
FAU - Rewers, Marian J
AU  - Rewers MJ
FAU - Gottlieb, Peter A
AU  - Gottlieb PA
FAU - Barker, Jennifer M
AU  - Barker JM
FAU - Eisenbarth, George S
AU  - Eisenbarth GS
LA  - eng
GR  - N01AI15416/AI/NIAID NIH HHS/United States
GR  - M01 RR000069/RR/NCRR NIH HHS/United States
GR  - R37 DK032493/DK/NIDDK NIH HHS/United States
GR  - K12 HD000850/HD/NICHD NIH HHS/United States
GR  - AI050864/AI/NIAID NIH HHS/United States
GR  - U19 AI050864/AI/NIAID NIH HHS/United States
GR  - M01 RR000051/RR/NCRR NIH HHS/United States
GR  - MO1RR00069/RR/NCRR NIH HHS/United States
GR  - R37 DK032083/DK/NIDDK NIH HHS/United States
GR  - R01 DK032493/DK/NIDDK NIH HHS/United States
GR  - MO1 RR00051/RR/NCRR NIH HHS/United States
GR  - K12-HD000850/HD/NICHD NIH HHS/United States
GR  - P30 DK057516/DK/NIDDK NIH HHS/United States
GR  - R01 DK032083/DK/NIDDK NIH HHS/United States
GR  - AI15416/AI/NIAID NIH HHS/United States
GR  - DK32493/DK/NIDDK NIH HHS/United States
GR  - DK32083/DK/NIDDK NIH HHS/United States
GR  - P30 DK57516/DK/NIDDK NIH HHS/United States
GR  - U01 DK062418/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110511
PL  - United States
TA  - J Clin Endocrinol Metab
JT  - The Journal of clinical endocrinology and metabolism
JID - 0375362
RN  - 0 (Autoantibodies)
RN  - 0 (HLA-B Antigens)
RN  - 0 (HLA-B15 Antigen)
RN  - EC 1.14.14.16 (Steroid 21-Hydroxylase)
SB  - IM
MH  - Addison Disease/*genetics/immunology
MH  - Adult
MH  - Alleles
MH  - Autoantibodies/*genetics/immunology
MH  - Female
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - HLA-B Antigens/*genetics/immunology
MH  - HLA-B15 Antigen
MH  - Haplotypes
MH  - Humans
MH  - Male
MH  - Polymorphism, Single Nucleotide
MH  - Steroid 21-Hydroxylase/*genetics/immunology
PMC - PMC3135206
EDAT- 2011/05/14 06:00
MHDA- 2011/09/13 06:00
PMCR- 2012/07/01
CRDT- 2011/05/14 06:00
PHST- 2011/05/14 06:00 [entrez]
PHST- 2011/05/14 06:00 [pubmed]
PHST- 2011/09/13 06:00 [medline]
PHST- 2012/07/01 00:00 [pmc-release]
AID - jc.2010-2964 [pii]
AID - 10-2964 [pii]
AID - 10.1210/jc.2010-2964 [doi]
PST - ppublish
SO  - J Clin Endocrinol Metab. 2011 Jul;96(7):2154-62. doi: 10.1210/jc.2010-2964. Epub 
      2011 May 11.