Iron loading in <i>HFE p.C282Y</i> homozygotes found by population screening: relationships to HLA-type and T-lymphocyte subsets

<p>Iron loading in <i>p.C282Y</i> homozygous HFE hemochromatosis subjects is highly variable, and it is unclear what factors cause this variability. Finding such factors could aid in predicting which patients are at highest risk and require closest follow-up. The degree of iron loading has previously been associated with certain HLA-types and with abnormally low CD8 + cell counts in peripheral blood. In 183 Norwegian, <i>p.C282Y</i> homozygotes (104 men, 79 women) originally found through population screening we determined HLA type and measured total T-lymphocytes, CD4 + and CD8 + cells, and compared this with data on iron loading. In <i>p.C282Y</i> homozygous men, but not in homozygous women, we found that the presence of two <i>HLA-A*03</i> alleles increased the iron load on average by approximately 2-fold compared to <i>p.C282Y</i> homozygous men carrying zero or one <i>A*03</i> allele. On the other hand, the presence of two <i>HLA-A*01</i> alleles, in male subjects, apparently reduced the iron loading. In <i>p.C282Y</i> homozygous individuals, the iron loading was increased if the CD8 + cell number was below the 25 percentile or if the CD4 + cell number was above the 75 percentile. This effect appeared to be additive to the effect of the number of <i>HLA-A*03</i> alleles. Our data indicate that homozygosity for the <i>HLA-A*03</i> allele significantly increases the risk of excessive iron loading in Norwegian <i>p.C282Y</i> homozygous male patients. In addition, low CD8 + cell number or high CD4 + cell number further increases the risk of excessive iron loading.</p>