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Key findings to expedite the diagnosis of hyper‐IgE syndromes in infants and young children
Author(s) -
Hagl Beate,
Heinz Valerie,
Schlesinger Anne,
Spielberger Benedikt D.,
SawalleBelohradsky Julie,
SennRauh Monika,
Magg Thomas,
Boos Annette C.,
Hönig Manfred,
Schwarz Klaus,
Dückers Gregor,
Bernuth Horst,
Pache Christoph,
KaritnigWeiss Cäcilia,
Belohradsky Bernd H.,
Frank Josef,
Niehues Tim,
Wahn Volker,
Albert Michael H.,
Wollenberg Andreas,
Jansson Annette F.,
Renner Ellen D.
Publication year - 2016
Publication title -
pediatric allergy and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.269
H-Index - 89
eISSN - 1399-3038
pISSN - 0905-6157
DOI - 10.1111/pai.12512
Subject(s) - medicine , atopic dermatitis , immunology , immunoglobulin e , primary immunodeficiency , allergy , asthma , antibody , immune system
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 STAT 3 and DOCK 8 . Methods Here, we assess the clinical and immunologic phenotype of DOCK 8‐ and STAT 3‐ 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 DOCK 8‐ HIES , T‐cell lymphopenia and low IFN ‐gamma secretion after stimulation were common, likely promoting viral infections. In contrast to STAT 3‐ HIES , DOCK 8‐ HIES patients showed more severe inflammation with regard to allergic manifestations, elevated activation markers ( HLA ‐ DR , CD 69, CD 86, and CD 154), and significantly increased inflammatory cytokines ( IL 1‐beta, IL 4, IL 6, 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.