Farmand Susan, Sundin Mikael
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.
Curr Opin Hematol. 2015 Jan;22(1):12-22. doi: 10.1097/MOH.0000000000000104.
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).
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.
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.
本综述概述了有关高免疫球蛋白E综合征（HIES）发病机制、诊断和临床护理的最新数据。HIES是一组具有重叠和独特特征的原发性免疫缺陷病，最常见的病因是信号转导和转录激活因子3（STAT3）或细胞分裂素8（DOCK8）缺乏。
在解读STAT3和DOCK8与B细胞、T细胞和自然杀伤细胞免疫的相关性以及理解过敏特征方面取得了特别进展。例如，STAT3缺陷型HIES的多系统特征，如反复骨折和骨质减少、高度血管病变和脑白质高信号，已得到充分表征。IgG替代疗法可能有助于STAT3缺陷型HIES的临床护理。在DOCK8缺陷型HIES中，早年的高发病率和死亡率似乎使异基因造血干细胞移植成为必要。也有新的HIES实体被报道。
最近的进展扩展了我们对HIES的理解，并改善了诊断和临床护理。然而，仍需要更多研究来充分阐明特定的感染易感性和肺部并发症，特别是在STAT3缺陷型HIES中。未来的研究还需要关注HIES非免疫特征的临床护理和治疗，以及探索治愈性治疗方法。
