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Blood, 15 December 2001, Vol. 98, No. 13, pp. 3513-3519
PLENARY PAPER
Increased frequency of HLA-DR2 in patients with paroxysmal
nocturnal hemoglobinuria and the PNH/aplastic anemia syndrome
Jaroslaw P. Maciejewski,
Dean Follmann,
Ryotaro Nakamura,
Yogen Saunthararajah,
Candido E. Rivera,
Toni Simonis,
Kevin E. Brown,
John A. Barrett, and
Neal S. Young
From the Hematology Branch and Office of Biostatistics
Research, National Heart, Lung and Blood Institute; and the
HLA-Laboratory, Department of Transfusion Medicine, and Department of
Laboratory Medicine, Hematology Section, Clinical Center, National
Institutes of Health, Bethesda, MD.
Many autoimmune diseases are associated with HLA alleles, and such
a relationship also has been reported for aplastic anemia (AA). AA and
paroxysmal nocturnal hemoglobinuria (PNH) are related clinically, and
glycophosphoinositol (GPI)-anchored protein (AP)-deficient cells can
be found in many patients 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 alleles was examined. The study involved
patients with a primary diagnosis of AA, patients with myelodysplastic
syndrome (MDS), and patients with primary PNH. Tests of proportions
were used to compare allelic frequencies. For patients with a PNH clone
(defined by the presence of GPI-AP-deficient granulocytes), regardless
of clinical manifestations, there was a higher than normal incidence of
HLA-DR2 (58% versus 28%; z = 4.05). The increased
presence of HLA-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 second cohort of patients with
bone marrow failure treated with immunosuppression 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 results suggest that clonal expansion of GPI-AP-deficient cells is linked to HLA and likely related to an immune mechanism.
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