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Inherited Susceptibility to Autoimmune Addison's Disease Is Linked to Juman Leukocyte Antigens-DR3 and/or DR4, except when Associated with Type I Autoimmune Poluglandular Syndrome^*

NOEL K. MACLAREN and WILLIAM J. RILEY

Departments of Pathology and Pediatrics, University of Florida, College of Medicine Gainesville, Florida 32610

Address requests for reprints to: Noel K. Maclaren, M.D., Department of Pathology, Box J-275, JHMHC, Gainesville, Florida 32610.

The inherited susceptibility to autoimmune Addison's disease was found to be strongly associated with human leukocyte antigens (HLA)-DR3 and DR4 alleles. In a study of 45 white patients from the United States with the disease, the relative risks (the number of times that an individual is at risk for Addison's disease if they had a marker, compared to those without such marker) were found to be 6.0, 4.6, and 26.5 for the DR3 allele, the DR4 allele, and for DR3/DR4 heterozygotes, respectively. Frequencies of DR2, DR5, and DR7 in the patients with Addison's disease were significantly decreased in comparison to 265 individuals in the control population. These HLA-DR frequencies in patients with Addison's disease were similar to those for 723 patients with insulin-dependent diabetes (IDD).

However, the above HLA-DR associations persisted even when only data from the 37 patients wit Addison's disease who did not have IDD were considered. Adrenocortical autoantibodies in 23 patients with IDD who did not have Addison's disease were equally frequent among those with DR4 and DR3 alleles. In contrast, HLA-DR frequencies in 17 patients with type I autoimmune polyglandular syndrome (chronic mucocutaneous moniliasis, hypoparathyroidism, Addision's disease, etc.) were not differnt from control. We conclude that genetic susceptibility to autoimmune Addison's disease may involve the same HLA-associated genetic determinants as IDD, except when Addison's disease occurs as part of type I autoimmune polyglandular syndrome.

^* This research was supported by Grants RR-082, HD-19469, and AM-36151 from the NIH, Grant 183439 from the Juvenile Diabetes Foundation, and grants from The Humana Hospital Corporation at Orlando, and the Kroc Foundation. Parts ofthis study were presented at the Second Joint Meeting of the Lawson Wilkins Society and European Society for Pediatric Endocrinology, Baltimore, Maryland, June 1984.

Supported by Career Development Award AM-01421 from the NIH.

Received August 8, 1985.

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