The immunological detection of a 21-OH deficiency mutation HLA supratype.

Previous studies have shown that the late-onset and cryptic forms of 21-hydroxylase deficiency are highly associated with the HLA supratype HLA-B14,C4A2,C4B1/2,DR1. Since cells from a number of unrelated normal individuals from different ethnic backgrounds expressing the DR1 associated with this supratype failed to stimulate two different DR1-restricted T-cell clones that proliferated in the presence of most other DR1 cells, we decided to test the hypothesis that cells with this supratype express "abnormal" DR1 molecules that have been affected in some way by the chromosomal mutation responsible for B14,DR1-associated 21-hydroxylase deficiency (21-OH-defL). The results showed an association between "abnormal" DR1 and 21-OH-defL (elevated rates of 17 alpha-hydroxyprogesterone [17-OHP] increase and elevated peak 17-OHP values following ACTH stimulation). The presence of the B14,DR1 supratype can be used to predict the presence of "abnormal" DR1 and the clinical status of individuals not previously known to be 21-OH-defL carriers.