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Blood, Vol. 93 No. 5 (March 1), 1999:
pp. 1651-1657
Clonality of Isolated Eosinophils in the Hypereosinophilic Syndrome
Hsiao-Wen Chang,
Kah-Hoo Leong,
Dow-Rhoon Koh, and
Szu-Hee Lee
From the Department of Pathology, the National University Medical
Institutes; the Department of Physiology, National University of
Singapore; and the Division of Haematology, National University
Hospital, Singapore.
The idiopathic hypereosinophilic syndrome (IHES) is a rare disorder
characterized by unexplained, persistent eosinophilia associated with
multiple organ dysfunction due to eosinophilic tissue infiltration. In
the absence of karyotypic abnormalities, there is no specific test to
detect clonal eosinophilia in IHES. Analysis of X-chromosome
inactivation patterns can be used to determine whether proliferative
disorders are clonal in origin. Methylation of HpaII and
Hha I sites near the polymorphic trinucleotide repeat of the
human androgen receptor gene (HUMARA) has been shown to correlate with
X-inactivation. In this study, we have used the polymerase chain
reaction (PCR) with nested primers to analyze X-inactivation patterns
of the HUMARA loci in purified eosinophils from female patients with
eosinophilia. Peripheral blood eosinophils were isolated by their
autofluoresence using flow cytometric sorting. Eosinophils purified
from a female patient presenting with IHES were found to show a clonal
pattern of X-inactivation. Eosinophil-depleted leukocytes from this
patient were polyclonal by HUMARA analysis, thus excluding skewedness
of random X-inactivation. After corticosteroid suppression of her blood
eosinophilia, a clonal population of eosinophils could no longer be
detected in purified eosinophils. In contrast, eosinophils purified
from a patient with Churg-Strauss syndrome and from six patients with
reactive eosinophilias attributed to allergy, parasitic infection, or
drug reaction showed a polyclonal pattern of X-inactivation by HUMARA
analysis. The finding of clonal eosinophilia in a patient presenting
with IHES indicates that such patients may have, in reality, a
low-grade clonal disorder that can be distinguished from reactive
eosinophilias by HUMARA analysis. Further, the method described can be
used to monitor disease progression.

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