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Unusual immunophenotype of CD8+ T cells in familial hemophagocytic lymphohistiocytosis
Journal article   Peer reviewed

Unusual immunophenotype of CD8+ T cells in familial hemophagocytic lymphohistiocytosis

Nitin J Karandikar, Steven H Kroft, Subramanian Yegappan, Beverly B Rogers, Victor M Aquino, Kyung-Mi Lee, Vinay Kumar, F. Javier Guenaga, Elaine S Jaffe, Daniel C Douek, …
Blood, Vol.104(7), pp.2007-2009
10/01/2004
DOI: 10.1182/blood-2004-04-1431
PMID: 15205266

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Abstract

Abstract Familial hemophagocytic lymphohistiocytosis (FHL) is an inherited, fatal disorder of infancy. We report here a 17-day-old female infant who presented with high fever, hepatosplenomegaly, hypertriglyceridemia, hypofibrinogenemia, thrombocytopenia, and liver failure. Leukocytosis was detected with circulating “atypical” lymphoid cells. Flow cytometric studies revealed expanded subpopulations of CD8+ T cells with unusual immunophenotypic features, including a subset that lacked CD5 expression. A liver biopsy showed hemophagocytic lymphohistiocytosis with exuberant infiltrates of CD8+ T cells that lacked perforin. Mutational studies revealed a 666C→A (H222Q) missense mutation in the perforin gene. T-cell receptor studies on flow-sorted T-cell subpopulations revealed no evidence of monoclonality. Analysis of T-cell receptor excision circle levels indicated long proliferative history in the aberrant CD8+ T-cell subsets. This case provides an instructive example of uncontrolled reactive proliferation of CD8+ T cells in FHL, resulting in atypical morphology and unusual immunophenotypic features that might suggest malignancy in other clinical settings.

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