Altered chemotactic response to CXCL12 in patients carrying GATA2 ă mutations

Anna Maciejewski-Duval, Floriane Meuris, Alexandre Bignon, Marie-Laure Aknin, Karl Balabanian, Laurence Faivre, Marlène Pasquet (), Vincent Barlogis, Claire Fieschi, Christine Bellanné-Chantelot, Jean Donadieu, Geraldine Schlecht-Louf, Viviana Marin-Esteban and Françoise Bachelerie ()
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Anna Maciejewski-Duval: RTMG - Régulation de la transcription et maladies génétiques - CNRS - Centre National de la Recherche Scientifique - CNRS - Centre National de la Recherche Scientifique
Alexandre Bignon: LabEX LERMIT - Laboratoire de Recherche sur le Médicament et l'Innovation Thérapeutique - INSERM - Institut National de la Santé et de la Recherche Médicale, Cytokines, chimiokines et immunopathologie - UP11 - Université Paris-Sud - Paris 11 - IFR13 - INSERM - Institut National de la Santé et de la Recherche Médicale
Karl Balabanian: Cytokines, chimiokines et immunopathologie - UP11 - Université Paris-Sud - Paris 11 - IFR13 - INSERM - Institut National de la Santé et de la Recherche Médicale
Laurence Faivre: GAD - Génétique des Anomalies du Développement - UB - Université de Bourgogne - IFR100 - Structure fédérative de recherche Santé-STIC
Marlène Pasquet: Sercice Hématologie, immunologie et oncologie pédiatrique [CHU Toulouse] - Pôle Enfants [CHU Toulouse] - CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
Vincent Barlogis: Pédiatrie et oncologie pédiatrique [Hôpital de la Timone - APHM] - AMU - Aix Marseille Université - APHM - Assistance Publique - Hôpitaux de Marseille - TIMONE - Hôpital de la Timone [CHU - APHM]
Claire Fieschi: Différenciation des cellules B, hémopathies, lymphoïdes et déficit de l'immunité humorale - UPD7 - Université Paris Diderot - Paris 7, Service d'immunologie clinique - AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) - UPD7 - Université Paris Diderot - Paris 7 - Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris] - AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP)
Christine Bellanné-Chantelot: CHU Pitié-Salpêtrière [AP-HP] - AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) - SU - Sorbonne Université
Jean Donadieu: Registre français des neutropénies chroniques sévères, CHU Trousseau [APHP] - AP-HP - Assistance publique - Hôpitaux de Paris (AP-HP) - SU - Sorbonne Université
Françoise Bachelerie: Cytokines, chimiokines et immunopathologie - UP11 - Université Paris-Sud - Paris 11 - IFR13 - INSERM - Institut National de la Santé et de la Recherche Médicale

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Abstract: GATA2 deficiency formerly described as MonoMAC syndrome; dendritic ă cells, monocytes, B cells, and natural killer cell deficiency; familial ă myelodysplastic syndrome/acute myeloid leukemia; or Emberger syndrome ă encompasses a range of hematologic and nonhematologic anomalies, mainly ă characterized by monocytopenia, B lymphopenia, natural killer cell ă cytopenia, neutropenia, immunodeficiency, and a high risk of developing ă acute myeloid leukemia. Herein, we present 7 patients with GATA2 ă deficiency recruited into the French Severe Chronic Neutropenia ă Registry, which enrolls patients with all kinds of congenital ă neutropenia. We performed extended immunophenotyping of their whole ă blood lymphocyte populations, together with the analysis of their ă chemotactic responses. Lymphopenia was recorded for B and CD4(+) T cells ă in 6 patients. Although only 3 patients displayed natural killer cell ă cytopenia, the CD56(bright) natural killer subpopulation was nearly ă absent in all 7 patients. Natural killer cells from 6 patients showed ă decreased CXCL12/CXCR4-dependent chemotaxis, whereas other lymphocytes, ă and most significantly B lymphocytes, displayed enhanced CXCL12induced ă chemotaxis compared with healthy volunteers. Surface expression of CXCR4 ă was significantly diminished in the patients' natural killer cells, ă although the total expression of the receptor was found to be equivalent ă to that of natural killer cells from healthy individual controls. ă Together, these data reveal that GATA2 deficiency is associated with ă impaired membrane expression and chemotactic dysfunctions of CXCR4. ă These dysfunctions may contribute to the physiopathology of this ă deficiency by affecting the normal distribution of lymphocytes and thus ă potentially affecting the susceptibility of patients to associated ă infections.

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Date: 2016-06
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Published in Journal of Leukocyte Biology, 2016, 99 (6), pp.1065-1076

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Persistent link: https://EconPapers.repec.org/RePEc:hal:journl:hal-01482522

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