Susan Farmand1, Mikael Sundin. 1. aDepartment of Microbiology, Tumor and Cell Biology bDivision of Pediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet cSection of Hematology, Immunology and HSCT, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden.
Abstract
PURPOSE OF REVIEW: This review provides an overview on recent data regarding pathogenesis, diagnostics and clinical care of hyper-IgE syndromes (HIES). HIES are a group of primary immunodeficiencies with overlapping and distinct features, most frequently caused by deficiency in signal transducer and activator of transcription 3 (STAT3) or dedicator of cytokinesis 8 (DOCK8). RECENT FINDINGS: Particular progress has been made in deciphering the relevance of STAT3 and DOCK8 for B-cell, T-cell and natural killer-cell immunity as well as in understanding allergic features. Multisystemic features of STAT3-deficient HIES, for example, recurrent fractures and osteopenia, a high degree of vasculopathy and brain white matter hyperintensities, have been thoroughly characterized. IgG replacement may add to the clinical care in STAT3-deficient HIES. In DOCK8-deficient HIES, the high morbidity and deaths in early age seem to justify allogeneic hematopoietic stem cell transplantation. New HIES entities have also been reported. SUMMARY: The recent advances expand our understanding of HIES, and improve the diagnostics and clinical care. Yet, more research is required to fully elucidate the specific infection susceptibilities and lung complications, particularly in STAT3-deficient HIES. Future studies also need to focus on clinical care and treatment of nonimmunologic features of HIES, as well as on exploring curative treatments.
PURPOSE OF REVIEW: This review provides an overview on recent data regarding pathogenesis, diagnostics and clinical care of hyper-IgE syndromes (HIES). HIES are a group of primary immunodeficiencies with overlapping and distinct features, most frequently caused by deficiency in signal transducer and activator of transcription 3 (STAT3) or dedicator of cytokinesis 8 (DOCK8). RECENT FINDINGS: Particular progress has been made in deciphering the relevance of STAT3 and DOCK8 for B-cell, T-cell and natural killer-cell immunity as well as in understanding allergic features. Multisystemic features of STAT3-deficient HIES, for example, recurrent fractures and osteopenia, a high degree of vasculopathy and brain white matter hyperintensities, have been thoroughly characterized. IgG replacement may add to the clinical care in STAT3-deficient HIES. In DOCK8-deficient HIES, the high morbidity and deaths in early age seem to justify allogeneic hematopoietic stem cell transplantation. New HIES entities have also been reported. SUMMARY: The recent advances expand our understanding of HIES, and improve the diagnostics and clinical care. Yet, more research is required to fully elucidate the specific infection susceptibilities and lung complications, particularly in STAT3-deficient HIES. Future studies also need to focus on clinical care and treatment of nonimmunologic features of HIES, as well as on exploring curative treatments.
Authors: Natalia I Dmitrieva; Avram D Walts; Dai Phuong Nguyen; Alex Grubb; Xue Zhang; Xujing Wang; Xianfeng Ping; Hui Jin; Zhen Yu; Zu-Xi Yu; Dan Yang; Robin Schwartzbeck; Clifton L Dalgard; Beth A Kozel; Mark D Levin; Russell H Knutsen; Delong Liu; Joshua D Milner; Diego B López; Michael P O'Connell; Chyi-Chia Richard Lee; Ian A Myles; Amy P Hsu; Alexandra F Freeman; Steven M Holland; Guibin Chen; Manfred Boehm Journal: J Clin Invest Date: 2020-08-03 Impact factor: 14.808
Authors: Ian A Myles; Erik D Anderson; Noah J Earland; Kol A Zarember; Inka Sastalla; Kelli W Williams; Portia Gough; Ian N Moore; Sundar Ganesan; Cedar J Fowler; Arian Laurence; Mary Garofalo; Douglas B Kuhns; Mark D Kieh; Arhum Saleem; Pamela A Welch; Dirk A Darnell; John I Gallin; Alexandra F Freeman; Steven M Holland; Sandip K Datta Journal: J Clin Invest Date: 2018-07-23 Impact factor: 14.808