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

Chantal Lagresle-Peyrou; Sonia Luce; Farid Ouchani; Tayebeh Shabi Soheili; Hanem Sadek; Myriam Chouteau; Amandine Durand; Isabelle Pic; Jacek Majewski; Chantal Brouzes; Nathalie Lambert; Armelle Bohineust; Els Verhoeyen; François-Loïc Cosset; Aude Magerus-Chatinet; Frédéric Rieux-Laucat; Virginie Gandemer; Delphine Monnier; Catherine Heijmans; Marielle van Gijn; Virgil A Dalm; Nizar Mahlaoui; Jean-Louis Stephan; Capucine Picard; Anne Durandy; Sven Kracker; Claire Hivroz; Nada Jabado; Geneviève de Saint Basile; Alain Fischer; Marina Cavazzana; Isabelle André-Schmutz

doi:10.1016/j.jaci.2016.04.032

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

Chantal Lagresle-Peyrou, Sonia Luce, Farid Ouchani, Tayebeh Shabi Soheili, Hanem Sadek, Myriam Chouteau, Amandine Durand, Isabelle Pic, Jacek Majewski, Chantal Brouzes, Nathalie Lambert, Armelle Bohineust, Els Verhoeyen, François-Loïc Cosset, Aude Magerus-Chatinet, Frédéric Rieux-Laucat, Virginie Gandemer, Delphine Monnier, Catherine Heijmans, Marielle van GijnVirgil A Dalm, Nizar Mahlaoui, Jean-Louis Stephan, Capucine Picard, Anne Durandy, Sven Kracker, Claire Hivroz, Nada Jabado, Geneviève de Saint Basile, Alain Fischer, Marina Cavazzana, Isabelle André-Schmutz

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

BACKGROUND: 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.

OBJECTIVE: We sought to characterize the genetic defect involved in a new form of X-linked immunodeficiency.

METHODS: We performed genetic analyses and an exhaustive phenotypic and functional characterization of the lymphocyte compartment.

RESULTS: We 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.

CONCLUSION: Our 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.

Original language	English
Pages (from-to)	1681–1689.e8
Journal	Journal of Allergy and Clinical Immunology
Volume	138
Issue number	6
DOIs	https://doi.org/10.1016/j.jaci.2016.04.032
Publication status	Published - Dec 2016

Keywords

Leukopenia
primary immunodeficiency
moesin
ezrin-radixin-moesin protein
adhesion
migration

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10.1016/j.jaci.2016.04.032

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Lagresle-Peyrou, C., Luce, S., Ouchani, F., Soheili, T. S., Sadek, H., Chouteau, M., Durand, A., Pic, I., Majewski, J., Brouzes, C., Lambert, N., Bohineust, A., Verhoeyen, E., Cosset, F.-L., Magerus-Chatinet, A., Rieux-Laucat, F., Gandemer, V., Monnier, D., Heijmans, C., ... André-Schmutz, I. (2016). X-linked primary immunodeficiency associated with hemizygous mutations in the moesin (MSN) gene. Journal of Allergy and Clinical Immunology, 138(6), 1681–1689.e8. https://doi.org/10.1016/j.jaci.2016.04.032

@article{5f8a04f35dc34ed4b02630d75c2aba25,

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

abstract = "BACKGROUND: 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.OBJECTIVE: We sought to characterize the genetic defect involved in a new form of X-linked immunodeficiency.METHODS: We performed genetic analyses and an exhaustive phenotypic and functional characterization of the lymphocyte compartment.RESULTS: We 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.CONCLUSION: Our 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.",

keywords = "Leukopenia, primary immunodeficiency, moesin, ezrin-radixin-moesin protein, adhesion, migration",

author = "Chantal Lagresle-Peyrou and Sonia Luce and Farid Ouchani and Soheili, {Tayebeh Shabi} and Hanem Sadek and Myriam Chouteau and Amandine Durand and Isabelle Pic and Jacek Majewski and Chantal Brouzes and Nathalie Lambert and Armelle Bohineust and Els Verhoeyen and Fran{\c c}ois-Lo{\"i}c Cosset and Aude Magerus-Chatinet and Fr{\'e}d{\'e}ric Rieux-Laucat and Virginie Gandemer and Delphine Monnier and Catherine Heijmans and {van Gijn}, Marielle and Dalm, {Virgil A} and Nizar Mahlaoui and Jean-Louis Stephan and Capucine Picard and Anne Durandy and Sven Kracker and Claire Hivroz and Nada Jabado and {de Saint Basile}, Genevi{\`e}ve and Alain Fischer and Marina Cavazzana and Isabelle Andr{\'e}-Schmutz",

year = "2016",

month = dec,

doi = "10.1016/j.jaci.2016.04.032",

language = "English",

volume = "138",

pages = "1681–1689.e8",

journal = "Journal of Allergy and Clinical Immunology",

issn = "0091-6749",

publisher = "Mosby Inc.",

number = "6",

}

Lagresle-Peyrou, C, Luce, S, Ouchani, F, Soheili, TS, Sadek, H, Chouteau, M, Durand, A, Pic, I, Majewski, J, Brouzes, C, Lambert, N, Bohineust, A, Verhoeyen, E, Cosset, F-L, Magerus-Chatinet, A, Rieux-Laucat, F, Gandemer, V, Monnier, D, Heijmans, C, van Gijn, M, Dalm, VA, Mahlaoui, N, Stephan, J-L, Picard, C, Durandy, A, Kracker, S, Hivroz, C, Jabado, N, de Saint Basile, G, Fischer, A, Cavazzana, M & André-Schmutz, I 2016, 'X-linked primary immunodeficiency associated with hemizygous mutations in the moesin (MSN) gene', Journal of Allergy and Clinical Immunology, vol. 138, no. 6, pp. 1681–1689.e8. https://doi.org/10.1016/j.jaci.2016.04.032

TY - JOUR

T1 - X-linked primary immunodeficiency associated with hemizygous mutations in the moesin (MSN) gene

AU - Lagresle-Peyrou, Chantal

AU - Luce, Sonia

AU - Ouchani, Farid

AU - Soheili, Tayebeh Shabi

AU - Sadek, Hanem

AU - Chouteau, Myriam

AU - Durand, Amandine

AU - Pic, Isabelle

AU - Majewski, Jacek

AU - Brouzes, Chantal

AU - Lambert, Nathalie

AU - Bohineust, Armelle

AU - Verhoeyen, Els

AU - Cosset, François-Loïc

AU - Magerus-Chatinet, Aude

AU - Rieux-Laucat, Frédéric

AU - Gandemer, Virginie

AU - Monnier, Delphine

AU - Heijmans, Catherine

AU - van Gijn, Marielle

AU - Dalm, Virgil A

AU - Mahlaoui, Nizar

AU - Stephan, Jean-Louis

AU - Picard, Capucine

AU - Durandy, Anne

AU - Kracker, Sven

AU - Hivroz, Claire

AU - Jabado, Nada

AU - de Saint Basile, Geneviève

AU - Fischer, Alain

AU - Cavazzana, Marina

AU - André-Schmutz, Isabelle

PY - 2016/12

Y1 - 2016/12

N2 - BACKGROUND: 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.OBJECTIVE: We sought to characterize the genetic defect involved in a new form of X-linked immunodeficiency.METHODS: We performed genetic analyses and an exhaustive phenotypic and functional characterization of the lymphocyte compartment.RESULTS: We 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.CONCLUSION: Our 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.

AB - BACKGROUND: 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.OBJECTIVE: We sought to characterize the genetic defect involved in a new form of X-linked immunodeficiency.METHODS: We performed genetic analyses and an exhaustive phenotypic and functional characterization of the lymphocyte compartment.RESULTS: We 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.CONCLUSION: Our 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.

KW - Leukopenia

KW - primary immunodeficiency

KW - moesin

KW - ezrin-radixin-moesin protein

KW - adhesion

KW - migration

U2 - 10.1016/j.jaci.2016.04.032

DO - 10.1016/j.jaci.2016.04.032

M3 - Article

C2 - 27405666

SN - 0091-6749

VL - 138

SP - 1681–1689.e8

JO - Journal of Allergy and Clinical Immunology

JF - Journal of Allergy and Clinical Immunology

IS - 6

ER -

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

Abstract

Keywords

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