Clonality of isolated eosinophils in the hypereosinophilic syndrome

The idiopathic hypereosinophilic syndrome (IHES) is a rare disorder charact erized by unexplained, persistent eosinophilia associated with multiple org an dysfunction due to eosinophilic tissue infiltration. In the absence of k aryotypic abnormalities, there is no specific test to detect clonal eosinop hilia in IHES. Analysis of X-chromosome inactivation patterns can be used t o determine whether proliferative disorders are clonal in origin. Methylati on of HpalI and Hha I sites near the polymorphic trinucleotide repeat of th e human androgen receptor gene (HUMARA) has been shown to correlate with X- inactivation. In this study, we have used the polymerase chain reaction (PC R) with nested primers to analyze X-inactivation patterns of the HUMARA loc i in purified eosinophils from female patients with eosinophilia. Periphera l blood eosinophils were isolated by their autofluoresence using flow cytom etric sorting. Eosinophils purified from a female patient presenting with I HES were found to show a clonal pattern of X-inactivation. Eosinophil-deple ted leukocytes from this patient were polyclonal by HUMARA analysis, thus e xcluding skewedness of random X-inactivation. After corticosteroid suppress ion of her brood eosinophilia, a clonal population of eosinophils could no longer be detected in purified eosinophils. In contrast, eosinophils purifi ed from a patient with Churg-Strauss syndrome and from six patients with re active eosinophilias attributed to allergy parasitic infection, or drug rea ction 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. Furthe r, the method described can be used to monitor disease progression. (C) 199 9 by The American Society of Hematology.