Increased frequency of HLA-DR2 in patients with paroxysmal nocturnal hemoglobinuria and the PNH/aplastic anemia syndrome

Many autoimmune diseases are associated with HLA alleles, and such a relati onship also has been reported for aplastic anemia (AA). AA and paroxysmal n octurnal hemoglobinuria (PNH) are related clinically, and glycophosphoinosi tol (GPI)-anchored protein (AP)-deficient cells can be found in many patien ts with AA. The hypothesis was considered that expansion of a PNH clone may be a marker of immune-mediated disease and its association with HLA allele s was examined. The study involved patients with a primary diagnosis of AA, patients with myelodysplastic syndrome (MDS), and patients with primary PN H. Tests of proportions were used to compare allelic frequencies. For patie nts with a PNH clone (defined by the presence of GPI-AP-deficient granulocy tes), regardless of clinical manifestations, there was a higher than normal incidence of HLA-DR2 (58% versus 28%; z = 4.05). The increased presence of HILA-DR2 was found in all frankly hemolytic PNH and in PNH associated with bone marrow failure (AA/PNH and MDS/PNH). HLA-DR2 was more frequent in AA/ PNH (56%) than in AA without a PNH clone (37%; z = 3.36). Analysis of a sec ond cohort of patients with bone marrow failure treated with immunosuppress ion showed that HLA-DR2 was associated with a hematologic response (50% of responders versus 34% of nonresponders; z = 2.69). Both the presence of HLA -DR2 and the PNH clone were independent predictors of response but the size of PNH clone did not correlate with improvement in blood count. The result s suggest that clonal expansion of GPI-AP-deficient cells is linked to HLA and likely related to an immune mechanism. (C) 2001 by The American Society of Hematology.