The syndrome of hemophagocytic lymphohistiocytosis in primary immunodeficiencies: implications for differential diagnosis and pathogenesis.

Autor:	Bode SF; Center of Chronic Immunodeficiency, University Medical Center Freiburg, Germany Center for Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Germany., Ammann S; Center of Chronic Immunodeficiency, University Medical Center Freiburg, Germany Faculty of Biology, University of Freiburg, Germany., Al-Herz W; Department of Pediatrics, Faculty of Medicine, Kuwait University, Safat, Kuwait., Bataneant M; Discipline of Pediatrics III, Victor Babes University of Medicine and Pharmacy Timisoara, Romania., Dvorak CC; Pediatric Allergy, Immunology and Blood and Marrow Transplant Division, UCSF, Benioff Children's Hospital, San Francisco, California, USA., Gehring S; Center for Pediatrics and Adolescent Medicine, Mainz, Germany., Gennery A; Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, UK., Gilmour KC; Camelia Botnar Laboratories, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK., Gonzalez-Granado LI; Immunodeficiencies Unit, Hematology & Oncology Unit, Pediatrics, Hospital 12 Octubre, Madrid, Spain., Groß-Wieltsch U; Pediatric Hematology, Oncology and Immunology, Olga Hospital, Stuttgart, Germany., Ifversen M; Department of Pediatrics, Copenhagen University Hospital, Rigshospitalet, Denmark., Lingman-Framme J; Department of Pediatrics, Halland Hospital, Halmstad, Sweden., Matthes-Martin S; St Anna Children's Hospital, Vienna, Austria., Mesters R; Department of Medicine/Hematology and Oncology, University Hospital Muenster, Germany., Meyts I; Department of Pediatrics, Department of Micriobiology and Immunology, University Hospitals Leuven, Katholieke Universiteit Leuven, Belgium., van Montfrans JM; Department of Pediatric Immunology, Wilhelmina Children's, Hospital/University Medical Centre Utrecht, The Netherlands., Pachlopnik Schmid J; Jeffrey Modell Diagnostic Center for Primary Immunodeficiencies, University Children's Hospital Zurich, Switzerland., Pai SY; Division of Hematology-Oncology, Boston Children's Hospital and Department of Pediatric Oncology, Dana-Farber Children's Hospital, Boston, Massachusetts, USA., Soler-Palacin P; Pediatric Infectious Diseases and Immunodeficiencies Unit. Hospital Universitari Vall d'Hebron, Universitat Autònoma de Barcelona, Spain., Schuermann U; Children's Hospital of Datteln, University of Witten-Herdecke, Datteln, Germany., Schuster V; Hospital for Children and Adolescents, University of Leipzig, Germany., Seidel MG; Pediatric Hematology-Oncology, Medical University of Graz, Austria., Speckmann C; Center of Chronic Immunodeficiency, University Medical Center Freiburg, Germany Center for Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Germany., Stepensky P; Pediatric Hematology-Oncology and Bone Marrow Transplantation, Hadassah Hebrew University Hospital, Jerusalem, Israel., Sykora KW; Pediatric Hematology-Oncology, Medical School Hannover, Germany., Tesi B; Childhood Cancer Research Unit, Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden., Vraetz T; Center for Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Germany., Waruiru C; Sheffield Children's Hospital, NHS Foundation Trust, UK., Bryceson YT; Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, University Hospital Huddinge, Stockholm, Sweden., Moshous D; Unit for Pediatric Immunology, Hematology and Rheumatology (UIHR), Hôpital Necker-Enfants Malades, Paris, France., Lehmberg K; Department of Hematology and Oncology, Children's Hospital, University of Hamburg, Germany., Jordan MB; Division of Bone Marrow Transplantation and Immunodeficiency, Cincinnati Children's Hospital Medical Center, University of Cincinnati Medical School, Ohio, USA., Ehl S; Center of Chronic Immunodeficiency, University Medical Center Freiburg, Germany Center for Pediatrics and Adolescent Medicine, University Medical Center Freiburg, Germany stephan.ehl@uniklinik-freiburg.de.
Jazyk:	angličtina
Zdroj:	Haematologica [Haematologica] 2015 Jul; Vol. 100 (7), pp. 978-88. Date of Electronic Publication: 2015 May 28.
DOI:	10.3324/haematol.2014.121608
Abstrakt:	Hemophagocytic lymphohistiocytosis is a hyperinflammatory syndrome defined by clinical and laboratory criteria. Current criteria were created to identify patients with familial hemophagocytic lmyphohistiocytosis in immediate need of immunosuppressive therapy. However, these criteria also identify patients with infection-associated hemophagocytic inflammatory states lacking genetic defects typically predisposing to hemophagocytic lymphohistiocytosis. These patients include those with primary immunodeficiencies, in whom the pathogenesis of the inflammatory syndrome may be distinctive and aggressive immunosuppression is contraindicated. To better characterize hemophagocytic inflammation associated with immunodeficiencies, we combined an international survey with a literature search and identified 63 patients with primary immunodeficiencies other than cytotoxicity defects or X-linked lymphoproliferative disorders, presenting with conditions fulfilling current criteria for hemophagocytic lymphohistiocytosis. Twelve patients had severe combined immunodeficiency with <100/μL T cells, 18 had partial T-cell deficiencies; episodes of hemophagocytic lymphohistiocytosis were mostly associated with viral infections. Twenty-two patients had chronic granulomatous disease with hemophagocytic episodes mainly associated with bacterial infections. Compared to patients with cytotoxicity defects, patients with T-cell deficiencies had lower levels of soluble CD25 and higher ferritin concentrations. Other criteria for hemophagocytoc lymphohistiocytosis were not discriminative. Thus: (i) a hemophagocytic inflammatory syndrome fulfilling criteria for hemophagocytic lymphohistiocytosis can be the initial manifestation of primary immunodeficiencies; (ii) this syndrome can develop despite severe deficiency of T and NK cells, implying that the pathophysiology is distinct and not appropriately described as "lympho"-histiocytosis in these patients; and (iii) current criteria for hemophagocytoc lymphohistiocytosis are insufficient to differentiate hemophagocytic inflammatory syndromes with different pathogeneses. This is important because of implications for therapy, in particular for protocols targeting T cells. (Copyright© Ferrata Storti Foundation.)
Databáze:	MEDLINE
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