Issue Archive

Idiopathic aplastic anemia (IAA) is a hematopoietic stem cell disorder mediated by autoimmune T cells, with bone marrow destruction being class 1 HLA restricted. Pagliuca et al analyzed the molecular landscape of HLA complexes of 300 patients with IAA and 10 times as many controls. They found that class 2 loci in IAA have abnormally low structural divergence and that this pattern contributes to decreasing T-cell receptor diversity, favoring cross-reactivity and perhaps partially explaining autoimmunity.

The immunopathology of idiopathic aplastic anemia (IAA) remains to be fully explained. In this month’s CME article, Zaimoku and colleagues report advances in our knowledge from studying over 400 patients, finding HLA class 1 allele loss in 22% of patients. In this cohort, loss of HLA expression and specific HLA genotypes are correlated with clinical manifestations, especially age of onset and clonal evolution. These data suggest that HLA genotype may be predictive for high-risk malignant clonal evolution.