Quantitative profiling of cytokines and chemokines in DOCK8‐deficient and atopic dermatitis patients

Abstract

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 DOCK8 protein is potentially a life-threatening autosomal recessive HIES and only curable with bone marrow transplantation. Hence, the diagnosis of DOCK8 deficiency is critical and should be sought at an early stage to initiate definitive therapy.Methods: Serum samples from patients with DOCK8 deficiency and atopic dermatitis were profiled on a cytokine/chemokine panel for potential differential expression.Results: CXCL10 and TNF-A were upregulated in DOCK8 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 DOCK8-deficient and AD patients, while IL-31 expression was comparable between both DOCK8-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 DOCK8-deficient and AD patients. The unique expression profile of various inflammatory cytokines in patients with DOCK8 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 DOCK8 deficiency through a potential shared pathway. In addition, these novel biomarkers may be potentially useful in distinguishing DOCK8 deficiency from AD allowing early-targeted treatment options. K E Y W O R D S atopic dermatitis, CXCL10, DOCK8, epidermal growth factor, hyper-IgE syndrome Abbreviations: EGF, epidermal growth factor; EPAS1, endothelial PAS domain protein 1; GCSF, CSF3 is colony-stimulating factor3; HIES, hyper-IgE syndrome; IL-31, interleukin-31; MDC, macrophage-derived chemokine; OPLS-DA, orthogonal projections to latent structures discriminant analysis; PGM3, phosphoglucomutase 3; STAT3, signal transducer activator of transcription 3; TNF, tumor necrosis factor.

Targeted Metabolomics Analysis on Obstructive Sleep Apnea Patients after Multilevel Sleep Surgery

“…The biomarker and the ratio between the top 20 candidates were selected using the area-under-the-curve (AUC) of the Receiver Operating Characteristic (ROC) analysis, with a sample classification based on PLSDA with a latent number 2 [ 34 , 35 ]. The sample-set was first divided into a test set containing 70% of injections, and a validation set with the remaining 30%.…”

Metabolomics Distinguishes DOCK8 Deficiency from Atopic Dermatitis: Towards a Biomarker Discovery

“…The mean red blood cells (RBC) and white blood cellsWBC counts in DOCK8-deficient patients were 4.5 ± 0.5 (10 12 /L) and 10.53 ± 2.3 (10 9 /L), respectively, whereas in AD patients, they were 5.3 ± 0.16 (10 12 /L) and 6.74 ± 0.9 (10 9 /L), respectively. The Severity Scoring of Atopic Dermatitis (SCORAD) and the Visual Analogue Scale (VAS) pruritus scores were calculated for both DOCK8-deficient and AD groups (Table S1) (table was reproduced with permission) [16].…”

“…Apart from cytokine biomarkers capable of distinguishing DOCK8-deficient from AD patients [16], definitive metabolomics biomarkers have not been identified yet. Therefore, we aimed to employ in-depth metabolomics technologies to study the metabolomic profiles of a cohort of patients with DOCK8 deficiency and severe AD to explore biomarkers that potentially reflect disease pathogenesis and may contribute towards improved disease monitoring, and ultimately novel clinical interventions.…”

Therapeutic effect of EGF secreted by human umbilical cord blood-derived mesenchymal stem cells on atopic dermatitis

“…In addition, there is increasing evidence that the EGFR pathway is an important signal transducer in skin biology and has a major impact on in ammatory/immune reactions of the skin [11][12][13][14]. In accordance with the ndings regarding EGFR expression, the serum level of EGF is also signi cantly downregulated in AD patients [15]. EGF plays an essential role in the dermal wound-healing process and stabilization of mast cell degranulation [12].…”