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Disease Progression of WHIM Syndrome in an International Cohort of 66 Pediatric and Adult Patients.
Geier, Christoph B; Ellison, Maryssa; Cruz, Rachel; Pawar, Sumit; Leiss-Piller, Alexander; Zmajkovicova, Katarina; McNulty, Shannon M; Yilmaz, Melis; Evans, Martin Oman; Gordon, Sumai; Ujhazi, Boglarka; Wiest, Ivana; Abolhassani, Hassan; Aghamohammadi, Asghar; Barmettler, Sara; Bhar, Saleh; Bondarenko, Anastasia; Bolyard, Audrey Anna; Buchbinder, David; Cada, Michaela; Cavieres, Mirta; Connelly, James A; Dale, David C; Deordieva, Ekaterina; Dorsey, Morna J; Drysdale, Simon B; Ehl, Stephan; Elfeky, Reem; Fioredda, Francesca; Firkin, Frank; Förster-Waldl, Elizabeth; Geng, Bob; Goda, Vera; Gonzalez-Granado, Luis; Grunebaum, Eyal; Grzesk, Elzbieta; Henrickson, Sarah E; Hilfanova, Anna; Hiwatari, Mitsuteru; Imai, Chihaya; Ip, Winnie; Jyonouchi, Soma; Kanegane, Hirokazu; Kawahara, Yuta; Khojah, Amer M; Kim, Vy Hong-Diep; Kojic, Marina; Koltan, Sylwia; Krivan, Gergely; Langguth, Daman.
Afiliación
  • Geier CB; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center University of Freiburg Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Ellison M; Department of Rheumatology and Clinical Immunology, Center for Chronic Immunodeficiency, Medical Center University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Cruz R; Division of Pediatric Allergy and Immunology, Department of Pediatrics, University of South Florida, St. Petersburg, FL, USA.
  • Pawar S; Division of Pediatric Allergy and Immunology, Department of Pediatrics, University of South Florida, St. Petersburg, FL, USA.
  • Leiss-Piller A; Morsani College of Medicine, University of South Florida, Tampa, FL, USA.
  • Zmajkovicova K; X4 Pharmaceuticals (Austria) GmbH, Vienna, Austria.
  • McNulty SM; Immunology Outpatient Clinic, Vienna, Austria.
  • Yilmaz M; X4 Pharmaceuticals (Austria) GmbH, Vienna, Austria.
  • Evans MO; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
  • Gordon S; Division of Pediatric Allergy and Immunology, Department of Pediatrics, University of South Florida, St. Petersburg, FL, USA.
  • Ujhazi B; Blanchfield Army Community Hospital, Fort Campbell, KY, USA.
  • Wiest I; Division of Pediatric Allergy and Immunology, Department of Pediatrics, University of South Florida, St. Petersburg, FL, USA.
  • Abolhassani H; Division of Pediatric Allergy and Immunology, Department of Pediatrics, University of South Florida, St. Petersburg, FL, USA.
  • Aghamohammadi A; X4 Pharmaceuticals (Austria) GmbH, Vienna, Austria.
  • Barmettler S; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
  • Bhar S; Division of Clinical Immunology, Department of Laboratory Medicine, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden.
  • Bondarenko A; Research Center for Immunodeficiencies, Pediatrics Center of Excellence, Children's Medical Center, Tehran University of Medical Sciences, Tehran, Iran.
  • Bolyard AA; Allergy and Clinical Immunology Unit, Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital, Boston, MA, USA.
  • Buchbinder D; Department of Pediatrics, Section of Hematology/Oncology and Critical Care Medicine, Bone Marrow Transplantation, Baylor College of Medicine, Texas Children's Hospital, Houston, TX, USA.
  • Cada M; Shupyk National Medical Academy of Postgraduate Education, Kyiv, Ukraine.
  • Cavieres M; Severe Chronic Neutropenia International Registry, University of Washington, Seattle, WA, USA.
  • Connelly JA; Division of Hematology, CHOC Children's Hospital, Orange, CA, USA.
  • Dale DC; Division of Hematology and Oncology, Hospital for Sick Children, Toronto, Ontario, Canada.
  • Deordieva E; Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
  • Dorsey MJ; Hematology Unit, Dr Luis Calvo Mackenna Children's Hospital, Santiago, Chile.
  • Drysdale SB; Vanderbilt University Medical Center, Nashville, TN, USA.
  • Ehl S; Department of Medicine, University of Washington, Seattle, WA, USA.
  • Elfeky R; Immunology, the Dmitry Rogachev National Medical Center of Pediatric Hematology, Oncology and Immunology, Moscow, Russia.
  • Fioredda F; Division of Allergy, Immunology and Blood and Marrow Transplantation, Department of Pediatrics, UCSF Benioff Children's Hospital, San Francisco, CA, USA.
  • Firkin F; Paediatric Infectious Diseases Research Group, St George's University Hospitals NHS Foundation Trust, London, UK.
  • Förster-Waldl E; Institute for Immunodeficiency, Center for Chronic Immunodeficiency, Medical Center University of Freiburg Faculty of Medicine, University of Freiburg, Freiburg, Germany.
  • Geng B; Department of Clinical Immunology, Royal Free Hospital, London, UK.
  • Goda V; Haematology Unit, IRCCS Istituto Giannina Gaslini, Genoa, Italy.
  • Gonzalez-Granado L; Department of Medicine, St Vincent's Hospital, University of Melbourne, Vic, Fitzroy, Australia.
  • Grunebaum E; Department of Clinical Haematology, St Vincent's Hospital, Vic, Fitzroy, Australia.
  • Grzesk E; Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
  • Henrickson SE; Division of Neonatology, Pediatric Intensive Care & Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria.
  • Hilfanova A; Center for Congenital Immunodeficiencies, Medical University of Vienna & Jeffrey Modell Diagnostic and Research Center, Vienna, Austria.
  • Hiwatari M; Divisions of Adult and Pediatric Allergy and Immunology, University of California, San Diego, CA, USA.
  • Imai C; Department for Pediatric Hematology and Hemopoietic Stem Cell Transplantation, Central Hospital of Southern Pest - National Institute of Hematology and Infectious Diseases, Budapest, Hungary.
  • Ip W; Immunodeficiencies Unit, Department of Pediatrics, University Hospital 12 de Octubre, Research Institute Hospital 12 Octubre, Madrid, Spain.
  • Jyonouchi S; Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada.
  • Kanegane H; Division of Immunology and Allergy, Hospital for Sick Children, Toronto, Ontario, Canada.
  • Kawahara Y; Department of Pediatrics, Hematology and Oncology Collegium Medicum, Bydgoszcz Nicolaus Copernicus University, Torun, Poland.
  • Khojah AM; Division of Allergy and Immunology, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
  • Kim VH; Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Kojic M; Institute for Immunology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Koltan S; Shupyk National Medical Academy of Postgraduate Education, Kyiv, Ukraine.
  • Krivan G; Department of Pediatrics, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
  • Langguth D; Department of Pediatrics, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
J Clin Immunol ; 42(8): 1748-1765, 2022 11.
Article en En | MEDLINE | ID: mdl-35947323
Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%). All variants affect the same CXCR4 region and impair CXCR4 internalization resulting in hyperactive signaling. The median age of diagnosis in our cohort (5.5 years) indicates WHIM syndrome can commonly present in childhood, although some patients are not diagnosed until adulthood. The prevalence and mean age of recognition and/or onset of clinical manifestations within our cohort were infections 88%/1.6 years, neutropenia 98%/3.8 years, lymphopenia 88%/5.0 years, and warts 40%/12.1 years. However, we report greater prevalence and variety of autoimmune complications of WHIM syndrome (21.2%) than reported previously. Patients with versus without family history of WHIM syndrome were diagnosed earlier (22%, average age 1.3 years versus 78%, average age 5 years, respectively). Patients with a family history of WHIM syndrome also received earlier treatment, experienced less hospitalization, and had less end-organ damage. This observation reinforces previous reports that early treatment for WHIM syndrome improves outcomes. Only one patient died; death was attributed to complications of hematopoietic stem cell transplantation. The variable expressivity of WHIM syndrome in pediatric patients delays their diagnosis and therapy. Early-onset bacterial infections with severe neutropenia and/or lymphopenia should prompt genetic testing for WHIM syndrome, even in the absence of warts.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Verrugas / Agammaglobulinemia / Síndromes de Inmunodeficiencia / Linfopenia / Neutropenia Tipo de estudio: Diagnostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: J Clin Immunol Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Países Bajos
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Verrugas / Agammaglobulinemia / Síndromes de Inmunodeficiencia / Linfopenia / Neutropenia Tipo de estudio: Diagnostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: J Clin Immunol Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Países Bajos