DOCK8 Deficiency: Clinical and Immunological Phenotype and Treatment Options - a Review of 136 Patients

Susanne E. Aydin; Sara Sebnem Kilic; Caner Aytekin; Ashish Kumar; Oscar Porras; Leena Kainulainen; Larysa Kostyuchenko; Ferah Genel; Necil Kütükcüler; Neslihan Karaca; Luis Gonzalez-Granado; Jordan Abbott; Daifulah Al-Zahrani; Nima Rezaei; Zeina Baz; Jens Thiel; Stephan Ehl; László Marodi; Jordan S. Orange; Julie Sawalle-Belohradsky; Sevgi Keles; Steven M. Holland; Özden Sanal; Deniz C. Ayvaz; Ilhan Tezcan; Hamoud Al-Mousa; Zobaida Alsum; Abbas Hawwari; Ayse Metin; Susanne Matthes-Martin; Manfred Hönig; Ansgar Schulz; Capucine Picard; Vincent Barlogis; Andrew Gennery; Marianne Ifversen; Joris van Montfrans; Taco Kuijpers; Robbert Bredius; Gregor Dückers; Waleed Al-Herz; Sung-Yun Pai; Raif Geha; Gundula Notheis; Carl-Philipp Schwarze; Betül Tavil; Fatih Azik; Kirsten Bienemann; Bodo Grimbacher; Valerie Heinz; H. Bobby Gaspar; Roland Aydin; Beate Hagl; Benjamin Gathmann; Bernd H. Belohradsky; Hans D. Ochs; Talal Chatila; Ellen D. Renner; Helen Su; Alexandra F. Freeman; Karin Engelhardt; Michael H. Albert; inborn errors working party of EBMT

doi:10.1007/s10875-014-0126-0

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DOCK8 Deficiency: Clinical and Immunological Phenotype and Treatment Options - a Review of 136 Patients

Journal article

Peer reviewed

DOCK8 Deficiency: Clinical and Immunological Phenotype and Treatment Options - a Review of 136 Patients

Susanne E. Aydin, Sara Sebnem Kilic, Caner Aytekin, Ashish Kumar, Oscar Porras, Leena Kainulainen, Larysa Kostyuchenko, Ferah Genel, Necil Kütükcüler, Neslihan Karaca, …

Journal of clinical immunology, Vol.35(2), pp.189-198

01/02/2015

DOI: https://doi.org/10.1007/s10875-014-0126-0

PMID: 25627830

Abstract

Biomedical and Life Sciences

Biomedicine

Immunology

Infectious Diseases

Internal Medicine

Medical Microbiology

Original Research

Mutations in DOCK8 result in autosomal recessive Hyper-IgE syndrome with combined immunodeficiency (CID). However, the natural course of disease, long-term prognosis, and optimal therapeutic management have not yet been clearly defined. In an international retrospective survey of patients with DOCK8 mutations, focused on clinical presentation and therapeutic measures, a total of 136 patients with a median follow-up of 11.3 years (1.3–47.7) spanning 1693 patient years, were enrolled. Eczema, recurrent respiratory tract infections, allergies, abscesses, viral infections and mucocutaneous candidiasis were the most frequent clinical manifestations. Overall survival probability in this cohort [censored for hematopoietic stem cell transplantation (HSCT)] was 87 % at 10, 47 % at 20, and 33 % at 30 years of age, respectively. Event free survival was 44, 18 and 4 % at the same time points if events were defined as death, life-threatening infections, malignancy or cerebral complications such as CNS vasculitis or stroke. Malignancy was diagnosed in 23/136 (17 %) patients (11 hematological and 9 epithelial cancers, 5 other malignancies) at a median age of 12 years. Eight of these patients died from cancer. Severe, life-threatening infections were observed in 79/136 (58 %); severe non-infectious cerebral events occurred in 14/136 (10 %). Therapeutic measures included antiviral and antibacterial prophylaxis, immunoglobulin replacement and HSCT. This study provides a comprehensive evaluation of the clinical phenotype of DOCK8 deficiency in the largest cohort reported so far and demonstrates the severity of the disease with relatively poor prognosis. Early HSCT should be strongly considered as a potential curative measure.

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Title: DOCK8 Deficiency: Clinical and Immunological Phenotype and Treatment Options - a Review of 136 Patients
Creators - without role: Susanne E. Aydin - Dr. von Haunersches Children’s Hospital, Ludwig-Maximilians-University
Sara Sebnem Kilic - Uludağ University
Caner Aytekin - Department of Pediatric Immunology, Dr. Sami Ulus Maternity and Children’s Health and Diseases Training and Research Hospital
Ashish Kumar - Cincinnati Children's Hospital Medical Center
Oscar Porras - Hospital Nacional de Niños
Leena Kainulainen - Turku University Hospital
Larysa Kostyuchenko - Pediatric Immunology, Western Ukrainian Specialized Children’s Medical Centre
Ferah Genel - Division of Pediatric Immunology, Behcet Uz State Hospital
Necil Kütükcüler - Ege University
Neslihan Karaca - Ege University
Luis Gonzalez-Granado - Pedriatrics, Immunodeficiencies Unit, Hospital 12 Octubre
Jordan Abbott - National Jewish Health
Daifulah Al-Zahrani - King Saud bin Abdulaziz University for Health Sciences
Nima Rezaei - Tehran University of Medical Sciences
Zeina Baz - Department of Pediatrics, St George Hospital University Medical Center
Jens Thiel - University of Freiburg
Stephan Ehl - University of Freiburg
László Marodi - University of Debrecen
Jordan S. Orange - Texas Children’s Hospital Center for Human Immunobiology
Julie Sawalle-Belohradsky - Dr. von Haunersches Children’s Hospital, Ludwig-Maximilians-University
Sevgi Keles - Necmettin Erbakan University
Steven M. Holland - National Institutes of Health
Özden Sanal - Hacettepe University
Deniz C. Ayvaz - Hacettepe University
Ilhan Tezcan - Hacettepe University
Hamoud Al-Mousa - Pediatric Allergy & Immunology, Department of Pediatrics, King Faisal Specialist Hospital & Research Center Riyadh
Zobaida Alsum - Department of Genetics, Research Center, MBC 03, King Faisal Specialist Hospital and Research Center
Abbas Hawwari - Department of Genetics, Research Center, MBC 03, King Faisal Specialist Hospital and Research Center
Ayse Metin - Ankara
Susanne Matthes-Martin - St Anna Children's Hospital
Manfred Hönig - Department of Pediatric Hematology/Oncology, University Childrens Hospital
Ansgar Schulz - Department of Pediatric Hematology/Oncology, University Childrens Hospital
Capucine Picard - Paris Descartes University
Vincent Barlogis - Aix-Marseille University
Andrew Gennery - Newcastle University
Marianne Ifversen - Rigshospitalet
Joris van Montfrans - University Hospital and Clinics
Taco Kuijpers - Academic Medical Center
Robbert Bredius - Pediatric SCT Unit and Laboratory for Immunology, Department of Pediatrics, LUMC
Gregor Dückers - Helios
Waleed Al-Herz - Kuwait University
Sung-Yun Pai - Dana-Farber Cancer Institute
Raif Geha - Boston Children's Hospital
Gundula Notheis - Dr. von Haunersches Children’s Hospital, Ludwig-Maximilians-University
Carl-Philipp Schwarze - Department of Pediatric Hematology/Oncology, University Childrens Hospital
Betül Tavil - Ankara
Fatih Azik - Ankara
Kirsten Bienemann - Department of Pediatric Hematology/Oncology, University Childrens Hospital
Bodo Grimbacher - University of Freiburg
Valerie Heinz - Dr. von Haunersches Children’s Hospital, Ludwig-Maximilians-University
H. Bobby Gaspar - UCL Australia
Roland Aydin - Dr. von Haunersches Children’s Hospital, Ludwig-Maximilians-University
Beate Hagl - Dr. von Haunersches Children’s Hospital, Ludwig-Maximilians-University
Benjamin Gathmann - University of Freiburg
Bernd H. Belohradsky - Dr. von Haunersches Children’s Hospital, Ludwig-Maximilians-University
Hans D. Ochs - University of Washington
Talal Chatila - Boston Children's Hospital
Ellen D. Renner - Dr. von Haunersches Children’s Hospital, Ludwig-Maximilians-University
Helen Su - Department of Rheumatology and Clinical Immunology, University Hospital Freiburg
Alexandra F. Freeman - Department of Rheumatology and Clinical Immunology, University Hospital Freiburg
Karin Engelhardt - University of Freiburg
Michael H. Albert - Dr. von Haunersches Children’s Hospital, Ludwig-Maximilians-University, Hauner University Childrens Hospital
inborn errors working party of EBMT
Publication Details: Journal of clinical immunology, Vol.35(2), pp.189-198
Publisher: Springer US
Identifiers: 9921798308331
Academic Unit: King Abdulaziz University; King Saud University; King Saud Bin Abdulaziz University for Health Sciences
Language: English
Resource Type: Journal article