Expanding the Clinical and Immunological Phenotypes and Natural History of MALT1 Deficiency.

Diarrhea Failure to Thrive Genetic Association Studies Hematopoietic Stem Cell Transplantation Humans Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein / genetics Phenotype Reinfection
Inborn errors of immunity MALT1 combined immune deficiency failure to thrive hematopoietic stem cell transplantation immune dysregulation primary immunodeficiency recurrent infections skin involvement

Journal

Journal of clinical immunology
ISSN: 1573-2592
Titre abrégé: J Clin Immunol
Pays: Netherlands
ID NLM: 8102137

Informations de publication

Date de publication:
04 2022
Historique:
received: 22 08 2021
accepted: 02 12 2021
pubmed: 27 1 2022
medline: 21 4 2022
entrez: 26 1 2022
Statut: ppublish

Résumé

MALT1 deficiency is a combined immune deficiency characterized by recurrent infections, eczema, chronic diarrhea, and failure to thrive. Clinical and immunological characterizations of the disease have not been previously reported in large cohorts. We sought to determine the clinical, immunological, genetic features, and the natural history of MALT-1 deficiency. The clinical findings and treatment outcomes were evaluated in nine new MALT1-deficient patients. Peripheral lymphocyte subset analyses, cytokine secretion, and proliferation assays were performed. We also analyzed ten previously reported patients to comprehensively evaluate genotype/phenotype correlation. The mean age of patients and disease onset were 33 ± 17 and 1.6 ± 0.7 months, respectively. The main clinical findings of the disease were recurrent infections (100%), skin involvement (100%), failure to thrive (100%), oral lesions (67%), chronic diarrhea (56%), and autoimmunity (44%). Eosinophilia and high IgE were observed in six (67%) and two (22%) patients, respectively. The majority of patients had normal T and NK cells, while eight (89%) exhibited reduced B cells. Immunoglobulin replacement and antibiotics prophylaxis were mostly ineffective in reducing the frequency of infections and other complications. One patient received hematopoietic stem cell transplantation (HSCT) and five patients died as a complication of life-threatening infections. Analyzing this cohort with reported patients revealed overall survival in 58% (11/19), which was higher in patients who underwent HSCT (P = 0.03). This cohort provides the largest analysis for clinical and immunological features of MALT1 deficiency. HSCT should be offered as a curative therapeutic option for all patients at the early stage of life.

Identifiants

DOI: 10.1007/s10875-021-01191-4 PMID: 35079916
pubmed: 35079916
doi: 10.1007/s10875-021-01191-4
pii: 10.1007/s10875-021-01191-4
doi:

Substances chimiques

MALT1 protein, human EC 3.4.22.-
Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein EC 3.4.22.-

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

634-652

Subventions

Organisme : Türkiye Bilimsel ve Teknolojik Araştirma Kurumu
ID : 318S202
Organisme : NIAID NIH HHS
ID : R01 AI085090
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI128976
Pays : United States
Organisme : Deutsche Forschungsgemeinschaft
ID : ID 360372040 - SFB 1335 P07

Informations de copyright

© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

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Auteurs

Asena Pinar Sefer (AP)

Division of Pediatric Allergy/Immunology, Marmara University, Istanbul, Turkey.
Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey.
Marmara University, The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey.

Hassan Abolhassani (H)

Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Division of Clinical Immunology, Department of Biosciences and Nutrition, Karolinska Institute, Stockholm, Sweden.
Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden.

Franziska Ober (F)

Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.

Basak Kayaoglu (B)

Department of Biological Sciences, Middle East Technical University, Ankara, Turkey.

Sevgi Bilgic Eltan (S)

Division of Pediatric Allergy/Immunology, Marmara University, Istanbul, Turkey.
Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey.
Marmara University, The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey.

Altan Kara (A)

TUBITAK Marmara Research Center, Gene Engineering and Biotechnology Institute, Gebze, Turkey.

Baran Erman (B)

Institute of Child Health, Hacettepe University, Ankara, Turkey.
Can Sucak Research Laboratory for Translational Immunology, Center for Genomics and Rare Diseases, Hacettepe University, Ankara, Turkey.

Naz Surucu Yilmaz (N)

Department of Biological Sciences, Middle East Technical University, Ankara, Turkey.

Cigdem Aydogmus (C)

Division of Pediatric Allergy and Immunology, University of Health Sciences, Basaksehir Cam Sakura City Hospital, Istanbul, Turkey.

Sezin Aydemir (S)

Faculty of Medicine, Pediatric Allergy and Immunology, Istanbul University-Cerrahpasa, Istanbul, Turkey.

Louis-Marie Charbonnier (LM)

Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Division of Immunology, Boston, MA, USA.

Burcu Kolukisa (B)

Division of Pediatric Allergy/Immunology, Marmara University, Istanbul, Turkey.
Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey.
Marmara University, The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey.

Gholamreza Azizi (G)

Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran.

Samaneh Delavari (S)

Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.

Tooba Momen (T)

Department of Allergy and Clinical Immunology, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non-Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran.

Simuzar Aliyeva (S)

Faculty of Medicine, Department of Pediatrics, Marmara University, Istanbul, Turkey.

Yasemin Kendir Demirkol (Y)

Division of Pediatric Genetics, University of Health Sciences, Umraniye Education and Research Hospital, Istanbul, Turkey.

Saban Tekin (S)

Hamidiye Faculty of Medicine, Department of Basic Medical Sciences, Division of Medical Biology, University of Health Sciences, Istanbul, Turkey.

Ayca Kiykim (A)

Faculty of Medicine, Pediatric Allergy and Immunology, Istanbul University-Cerrahpasa, Istanbul, Turkey.

Omer Faruk Baser (OF)

Faculty of Medicine, Pediatric Gastroenterology, Hepatology and Nutrition, Istanbul University-Cerrahpasa, Istanbul, Turkey.

Haluk Cokugras (H)

Faculty of Medicine, Pediatric Allergy and Immunology, Istanbul University-Cerrahpasa, Istanbul, Turkey.

Mayda Gursel (M)

Department of Biological Sciences, Middle East Technical University, Ankara, Turkey.

Elif Karakoc-Aydiner (E)

Division of Pediatric Allergy/Immunology, Marmara University, Istanbul, Turkey.
Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey.
Marmara University, The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey.

Ahmet Ozen (A)

Division of Pediatric Allergy/Immunology, Marmara University, Istanbul, Turkey.
Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey.
Marmara University, The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey.

Daniel Krappmann (D)

Research Unit Cellular Signal Integration, Institute of Molecular Toxicology and Pharmacology, Helmholtz Zentrum München - German Research Center for Environmental Health, Neuherberg, Germany.

Talal A Chatila (TA)

Boston Children's Hospital and Department of Pediatrics, Harvard Medical School, Division of Immunology, Boston, MA, USA.

Nima Rezaei (N)

Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
Primary Immunodeficiency Diseases Network (PIDNet), Universal Scientific Education and Research Network (USERN), Tehran, Iran.

Safa Baris (S)

Division of Pediatric Allergy/Immunology, Marmara University, Istanbul, Turkey. safabaris@hotmail.com.
Istanbul Jeffrey Modell Diagnostic and Research Center for Primary Immunodeficiencies, Istanbul, Turkey. safabaris@hotmail.com.
Marmara University, The Isil Berat Barlan Center for Translational Medicine, Istanbul, Turkey. safabaris@hotmail.com.
ORCID: 0000-0002-4730-9422

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Classifications MeSH

questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Signes et symptômes digestifs › Diarrhée › Expanding the Clinical and Immunological...
questionsmedicales.fr › États, signes et symptômes pathologiques › Signes et symptômes › Retard de croissance staturo-pondérale › Expanding the Clinical and Immunological...
questionsmedicales.fr › Techniques d'investigation › Techniques génétiques › Études d'associations génétiques › Expanding the Clinical and Immunological...
questionsmedicales.fr › Procédures de chirurgie opératoire › Transplantation › Transplantation cellulaire › Transplantation de cellules souches › Transplantation de cellules souches hématopoïétiques › Expanding the Clinical and Immunological...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Expanding the Clinical and Immunological...
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Ligases › Ubiquitin-protein ligase complexes › Ubiquitin-protein ligases › Protéine-1 de translocation de lymphome du tissu lymphoïde associé aux muqueuses › Expanding the Clinical and Immunological...
questionsmedicales.fr › Phénomènes génétiques › Phénotype › Expanding the Clinical and Immunological...
questionsmedicales.fr › États, signes et symptômes pathologiques › Processus pathologiques › Caractéristiques de la maladie › Récidive › Réinfection › Expanding the Clinical and Immunological...