128 INHERITED SUSCEPTIBILITY TO AUTOIMMUNE ADDLSON'S DISEASE IS LINKED TO HLA-DR3 AND DR4

Abstract

Inherited susceptibility to Addison's disease has been linked to the leukocyte antigen (HLA)-B8 allele, and by inference because of linkage disequilibrium between B8 and DR3, this susceptibility should be primarily to that of the DR3 antigen. Twenty four patients who had presented with overt Addison's disease, and another 28 patients who had been found to have adrenocortical autoantibodies, were HLA typed. Six of the Addisonian patients and 22 of the adrenal autoantibody positive patients had co-existing insulin dependent diabetes (IDD). In relation to HLA typing data from 253 Caucasian controls, Addison's disease was significantly associated with DR3 (X² 6.0 ; p = 0.014), DR4 (X² 7.4; p = 0.007) and DR3/DR4 heterozygosity (X² 25.4; p < 0.0001). Similiarly, adrenal autoantibodies in patients without Addison's disease (at the time of study) had increased frequencies of DR3 (X² 9.6; p = 0.003), DR4 (X² 12.6;p= 0.007) and DR3/DR4 (X² 15.2; p > 0.0001). Of the 6 Addison's patients who lacked DR3 and DR4 alleles in their HLA phenotype, 3 had type I autoimmune polyglandular syndrome.

In summary, these data indicate that susceptibility to autoimmune Addison's disease is associated with HLA-DR4 as well as DR3.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account

Continue with Google

Continue with ORCiD