BACKGROUND: Hyper-IgE syndromes (HIES) are primary immunodeficiency disorders characterized by elevated serum IgE, eczema, and recurrent infections. Despite the availability of confirmatory molecular diagnosis of several distinct HIES entities, the differentiation of HIES particularly from severe forms of atopic dermatitis remains a challenge. The two most common forms of HIES are caused by mutations in the genes STAT3 and DOCK8. METHODS: Here, we assess the clinical and immunologic phenotype of DOCK8- and STAT3-HIES patients including the cell activation, proliferation, and cytokine release after stimulation. RESULTS: Existing HIES scoring systems are helpful to identify HIES patients. However, those scores may fail in infants and young children due to the age-related lack of clinical symptoms. Furthermore, our long-term observations showed a striking variation of laboratory results over time in the individual patient. Reduced memory B-cell counts in concert with low specific antibody production are the most consistent findings likely contributing to the high susceptibility to bacterial and fungal infection. In DOCK8-HIES, T-cell lymphopenia and low IFN-gamma secretion after stimulation were common, likely promoting viral infections. In contrast to STAT3-HIES, DOCK8-HIES patients showed more severe inflammation with regard to allergic manifestations, elevated activation markers (HLA-DR, CD69, CD86, and CD154), and significantly increased inflammatory cytokines (IL1-beta, IL4, IL6, and IFN-gamma). CONCLUSION: Differentiating HIES from other diseases such as atopic dermatitis early in life is essential for patients because treatment modalities differ. To expedite the diagnosis process, we propose here a diagnostic workflow.
BACKGROUND:Hyper-IgE syndromes (HIES) are primary immunodeficiency disorders characterized by elevated serum IgE, eczema, and recurrent infections. Despite the availability of confirmatory molecular diagnosis of several distinct HIES entities, the differentiation of HIES particularly from severe forms of atopic dermatitis remains a challenge. The two most common forms of HIES are caused by mutations in the genes STAT3 and DOCK8. METHODS: Here, we assess the clinical and immunologic phenotype of DOCK8- and STAT3-HIESpatients including the cell activation, proliferation, and cytokine release after stimulation. RESULTS: Existing HIES scoring systems are helpful to identify HIES patients. However, those scores may fail in infants and young children due to the age-related lack of clinical symptoms. Furthermore, our long-term observations showed a striking variation of laboratory results over time in the individual patient. Reduced memory B-cell counts in concert with low specific antibody production are the most consistent findings likely contributing to the high susceptibility to bacterial and fungal infection. In DOCK8-HIES, T-cell lymphopenia and low IFN-gamma secretion after stimulation were common, likely promoting viral infections. In contrast to STAT3-HIES, DOCK8-HIES patients showed more severe inflammation with regard to allergic manifestations, elevated activation markers (HLA-DR, CD69, CD86, and CD154), and significantly increased inflammatory cytokines (IL1-beta, IL4, IL6, and IFN-gamma). CONCLUSION: Differentiating HIES from other diseases such as atopic dermatitis early in life is essential for patients because treatment modalities differ. To expedite the diagnosis process, we propose here a diagnostic workflow.
Authors: Zeinab A El-Sayed; Dalia H El-Ghoneimy; José A Ortega-Martell; Nesrine Radwan; Juan C Aldave; Waleed Al-Herz; Maryam A Al-Nesf; Antonio Condino-Neto; Theresa Cole; Brian Eley; Nahla H H Erwa; Sara Espinosa-Padilla; Emilia Faria; Nelson A Rosario Filho; Ramsay Fuleihan; Nermeen Galal; Elizabeth Garabedian; Mary Hintermeyer; Kohsuke Imai; Carla Irani; Ebtihal Kamal; Nadia Kechout; Adam Klocperk; Michael Levin; Tomas Milota; Monia Ouederni; Roberto Paganelli; Claudio Pignata; Farah N Qamar; Isabella Quinti; Sonia Qureshi; Nita Radhakrishnan; Nima Rezaei; John Routes; Surjit Singh; Sangeetha Siniah; Intisar Abdel-Hakam Taha; Luciana K Tanno; Ben Van Dort; Alla Volokha; Kathleen Sullivan Journal: World Allergy Organ J Date: 2022-06-17 Impact factor: 5.516
Authors: Joëlle Khourieh; Peng Zhang; Franck Rapaport; Qian Zhang; Anne Puel; Vivien Béziat; Jean-Laurent Casanova; Bertrand Boisson; Takaki Asano; András N Spaan; Juan Li; Wei-Te Lei; Simon J Pelham; David Hum; Maya Chrabieh; Ji Eun Han; Antoine Guérin; Joseph Mackie; Sudhir Gupta; Biman Saikia; Jamila E I Baghdadi; Ilham Fadil; Aziz Bousfiha; Tanwir Habib; Nico Marr; Luckshman Ganeshanandan; Jane Peake; Luke Droney; Andrew Williams; Fatih Celmeli; Nevin Hatipoglu; Tayfun Ozcelik; Capucine Picard; Laurent Abel; Stuart G Tangye; Stéphanie Boisson-Dupuis Journal: J Exp Med Date: 2021-06-17 Impact factor: 14.307