title: Expansion of CCR4+ activated T cells is associated with memory B cell reduction in DOCK8-deficient patients.
abstract: Hyper-IgE syndrome (HIES) is a genetic disorder characterized by elevated IgE serum levels, mostly due to mutations in STAT3 or DOCK8. Despite clinical heterogeneity between the two forms of the disease, clinical manifestations may not be conclusive for diagnosis and immunological differences are still unclear. Herein, we performed a detailed characterization of the T- and B-cell compartments by flow cytometry in seven HIES patients with homozygous DOCK8 mutations and six patients presenting heterozygous STAT3 mutations. We observed that DOCK8-deficient patients showed a marked reduction of naive and recent thymic emigrant (RTE) T lymphocytes together with a relative increase of activated T cells, most of which co-expressed the chemokine receptor CCR4, a marker of Th2 polarization. Moreover, an extreme reduction of memory B cells was detected, despite a normal/increased proportion of immunoglobulin-secreting cells. These observations indicate that DOCK8-deficient patients display a distinctive immunophenotype which is characteristic of this form of HIES.
authors.affiliation: Department of Clinical and Experimental Medicine, "Angelo Nocivelli" Institute for Molecular Medicine, University of Brescia, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Caracciolo
authors.affiliation: Laboratory of Genetic Disorders of Childhood, "Angelo Nocivelli" Institute for Molecular Medicine, Spedali Civili of Brescia, Brescia, Italy. Electronic address: daniele.moratto@gmail.com.
authors.forename: Daniele
authors.initials: D
authors.lastname: Moratto
authors.affiliation: Department of Clinical and Experimental Medicine, "Angelo Nocivelli" Institute for Molecular Medicine, University of Brescia, Italy; Scuola di Dottorato in Scienze della Riproduzione e dello Sviluppo, University of Trieste, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Giacomelli
authors.affiliation: Department of Clinical and Experimental Medicine, "Angelo Nocivelli" Institute for Molecular Medicine, University of Brescia, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Negri
authors.affiliation: Department of Clinical and Experimental Medicine, "Angelo Nocivelli" Institute for Molecular Medicine, University of Brescia, Italy.
authors.forename: Vassilios
authors.initials: V
authors.lastname: Lougaris
authors.affiliation: Oncoematologia Pediatrica of Brescia, Brescia, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Porta
authors.affiliation: Clinica Pediatrica dell'Università degli Studi di Messina, Messina, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pajno
authors.affiliation: Clinica Pediatrica dell'Università degli Studi di Messina, Messina, Italy.
authors.forename: Annamaria
authors.initials: A
authors.lastname: Salpietro
authors.affiliation: Division of Immunology, Rheumatology and Infectious Diseases, Department of Pediatrics, University of Torino, Torino, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Montin
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO, USA.
authors.forename: Darrell L
authors.initials: DL
authors.lastname: Dinwiddie
authors.affiliation: Center for Pediatric Genomic Medicine, Children's Mercy Hospital, Kansas City, MO, USA.
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Kingsmore
authors.affiliation: Department of Clinical and Experimental Medicine, "Angelo Nocivelli" Institute for Molecular Medicine, University of Brescia, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Plebani
authors.affiliation: Department of Clinical and Experimental Medicine, "Angelo Nocivelli" Institute for Molecular Medicine, University of Brescia, Italy.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Badolato
mesh_terms: D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000172:deficiency / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood; D007156:Immunologic Memory / Q000276:immunology*; D007589:Job Syndrome / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D008297:Male; D054398:Receptors, CCR4 / Q000276:immunology; D050796:STAT3 Transcription Factor / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology*; D055815:Young Adult
chemical_list: C515354:CCR4 protein, human; C516591:DOCK8 protein, human; D020662:Guanine Nucleotide Exchange Factors; D054398:Receptors, CCR4; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D007073:Immunoglobulin E
keywords: DOCK8; Hyper-IgE syndrome; Memory B cells; Recent thymic emigrants; Th2 commitment