X-linked primary immunodeficiency associated with hemizygous mutations in the moesin (MSN) gene

详细信息    查看全文

• 作者：Chantal Lagresle-Peyrou ; PhD^a ; ^b ; ^c ; Sonia Luce ; MSc^a ; ^b ; Farid Ouchani ; PhD^a ; ^b ; Tayebeh Shabi Soheili ; PhD^a ; ^b ; Hanem Sadek ; MSc^a ; ^b ; Myriam Chouteau ; MSc^a ; ^b ; Amandine Durand ; MSc^a ; ^b ; Isabelle Pic ; MSc^a ; ^b ; Jacek Majewski ; PhD^d ; Chantal Brouzes ; MD^e ; Nathalie Lambert ; MSc^f ; Armelle Bohineust ; PhD^g ; ^h ; Els Verhoeyen ; PhDⁱ ; ^j ; Franç ; ois-Loï ; c Cosset ; PhDⁱ ; Aude Magerus-Chatinet ; PhD^b ; ^k ; Fré ; dé ; ric Rieux-Laucat ; PhD^b ; ^k ; Virginie Gandemer ; MD ; PhD^l ; Delphine Monnier ; PhD^m ; Catherine Heijmans ; MDⁿ ; ^o ; Marielle van Gijn ; PhD^p ; Virgil A. Dalm ; MD^q ; Nizar Mahlaoui ; MD ; MSc^b ; ^r ; ^s ; ^t ; Jean-Louis Stephan ; MD^u ; Capucine Picard ; MD ; PhD^b ; ^f ; ^r ; ^s ; ^t ; Anne Durandy ; MD ; PhD^a ; ^b ; Sven Kracker ; PhD^a ; ^b ; Claire Hivroz ; PhD^g ; ^h ; Nada Jabado ; MD ; PhD^d ; ^v ; Geneviè ; ve de Saint Basile ; MD ; PhD^b ; ^f ; ^w ; Alain Fischer ; MD ; PhD^b ; ^r ; ^s ; ^x ; ^y ; Marina Cavazzana ; MD ; PhD^a ; ^b ; ^c ; Isabelle André ; -Schmutz ; PhD^a ; ^b ; ^c ; ^{isabelle.andre-schmutz@inserm.fr}
• 关键词：Leukopenia ; primary immunodeficiency ; moesin ; ezrin-radixin-moesin protein ; adhesion ; migration
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2016
• 出版时间：December 2016
• 年：2016
• 卷：138
• 期：6
• 页码：1681-1689.e8
• 全文大小：4100 K
• 卷排序：138

文摘

We investigated 7 male patients (from 5 different families) presenting with profound lymphopenia, hypogammaglobulinemia, fluctuating monocytopenia and neutropenia, a poor immune response to vaccine antigens, and increased susceptibility to bacterial and varicella zoster virus infections.ObjectiveWe sought to characterize the genetic defect involved in a new form of X-linked immunodeficiency.MethodsWe performed genetic analyses and an exhaustive phenotypic and functional characterization of the lymphocyte compartment.ResultsWe observed hemizygous mutations in the moesin (MSN) gene (located on the X chromosome and coding for MSN) in all 7 patients. Six of the latter had the same missense mutation, which led to an amino acid substitution (R171W) in the MSN four-point-one, ezrin, radixin, moesin domain. The seventh patient had a nonsense mutation leading to a premature stop codon mutation (R533X). The naive T-cell counts were particularly low for age, and most CD8+ T cells expressed the senescence marker CD57. This phenotype was associated with impaired T-cell proliferation, which was rescued by expression of wild-type MSN. MSN-deficient T cells also displayed poor chemokine receptor expression, increased adhesion molecule expression, and altered migration and adhesion capacities.ConclusionOur observations establish a causal link between an ezrin-radixin-moesin protein mutation and a primary immunodeficiency that could be referred to as X-linked moesin-associated immunodeficiency.