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Quantitative profiling of cytokines and chemokines in DOCK 8‐deficient and atopic dermatitis patients
Author(s) -
Jacob Minnie,
Bin Khalaf Duaa,
Alhissi Safa,
Arnout Rand,
Alsaud Bander,
AlMousa Hamoud,
Lopata Andreas L.,
Alazami Anas M.,
Dasouki Majed,
Abdel Rahman Anas M.
Publication year - 2019
Publication title -
allergy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.363
H-Index - 173
eISSN - 1398-9995
pISSN - 0105-4538
DOI - 10.1111/all.13610
Subject(s) - dock , immunology , atopic dermatitis , medicine , atopy , immune dysregulation , immunoglobulin e , cytokine , allergy , chemokine , immune system , biology , antibody , biochemistry
Background Hyper‐IgE syndromes ( HIES ) are a clinically overlapping, heterogeneous group of inborn errors of immunity characterized by elevated serum IgE level, eosinophilia, atopy, and immune dysregulation. Deficiency of DOCK 8 protein is potentially a life‐threatening autosomal recessive HIES and only curable with bone marrow transplantation. Hence, the diagnosis of DOCK 8 deficiency is critical and should be sought at an early stage to initiate definitive therapy. Methods Serum samples from patients with DOCK 8 deficiency and atopic dermatitis were profiled on a cytokine/chemokine panel for potential differential expression. Results CXCL 10 and TNF ‐A were upregulated in DOCK 8 patients when compared to AD , possibly contributing toward increased susceptibility to infections and cancer. In contrast, epidermal growth factor ( EGF ) was significantly downregulated in a subgroup of DOCK 8‐deficient and AD patients, while IL ‐31 expression was comparable between both DOCK 8‐deficient and AD cohorts, possibly contributing toward pruritus seen in both groups. Conclusion This comprehensive cytokine profile in HIES patients reveals distinctive biomarkers that differentiate between the DOCK 8‐deficient and AD patients. The unique expression profile of various inflammatory cytokines in patients with DOCK 8 deficiency vs atopic dermatitis likely reflects disease‐specific perturbations in multiple cellular processes and pathways leading to a predisposition to infections and allergies seen in these patients. These data agree with the role for EGF replacement therapy in EGF ‐deficient individuals with AD as well as DOCK 8 deficiency through a potential shared pathway. In addition, these novel biomarkers may be potentially useful in distinguishing DOCK 8 deficiency from AD allowing early‐targeted treatment options.