title: Good syndrome presenting with CD8⁺ T-Cell large granular lymphocyte leukemia.
abstract: Good Syndrome is an adult-onset combined immunodeficiency defined by hypogammaglobulinemia, low or absent number of B cells, T cell deficiency and thymic tumor. We have characterized CD8+ T cells from a patient with Good syndrome that presented with CD8+T-cell large granular lymphocytic leukemia (LGL). Characterization of peripheral blood CD8+ T cells revealed that majority of CD8+ T cells were terminally differentiated effector memory phenotype (TEMRA; CD8+CCR7-CD45RA+), and were PD-1high (CD279), ICOSlow (CD278), and granzymehigh. Almost all CD8+ T cells were IFN-γ+. CD8 Treg (CD8+CD183+CCR7+CD45RA-) were decreased. TEMRA phenotype along with CD279high, demonstrates that these are exhausted CD8+ T cells. This phenotype along with CD278low may also explain severe T cell functional deficiency in our patient. In the present patient, T-LGL appears to be a clonal expansion of CD279+granzyme+IFN-γ+CD8+TEMRA cells. To best of our knowledge this is the first case of CD8+T-cell LGL leukemia associated with Good syndrome.
authors.affiliation: Program in Primary Immunodeficiency and Aging, Division of Basic and Clinical Immunology, University of California at Irvine, Irvine, California, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Caperton
authors.affiliation: Program in Primary Immunodeficiency and Aging, Division of Basic and Clinical Immunology, University of California at Irvine, Irvine, California, USA.
authors.forename: Sudhanshu
authors.initials: S
authors.lastname: Agrawal
authors.affiliation: Program in Primary Immunodeficiency and Aging, Division of Basic and Clinical Immunology, University of California at Irvine, Irvine, California, USA.
authors.forename: Sudhir
authors.initials: S
authors.lastname: Gupta
mesh_terms: D000361:Agammaglobulinemia / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000276:immunology; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D054066:Leukemia, Large Granular Lymphocytic / Q000175:diagnosis / Q000276:immunology / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D016511:Severe Combined Immunodeficiency / Q000175:diagnosis / Q000276:immunology / Q000473:pathology*
keywords: ICOS; IFNgamma; PD-1; granzyme; memory T