Proteomics Profiling to Distinguish DOCK8 Deficiency From Atopic Dermatitis

Dedicator of cytokinesis 8 deficiency is an autosomal recessive primary immune deficiency disease belonging to the group of hyperimmunoglobulinemia E syndrome (HIES). The clinical phenotype of dedicator of cytokinesis 8 (DOCK8) deficiency, characterized by allergic manifestations, increased infectio...

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Autores principales:	Minnie Jacob, Afshan Masood, Zakiya Shinwari, Mai Abdel Jabbar, Hamoud Al-Mousa, Rand Arnaout, Bandar AlSaud, Majed Dasouki, Ayodele A. Alaiya, Anas M. Abdel Rahman
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	atopic dermatitis dedicator of cytokinesis (DOCK8) hyper IgE syndrome (HIES) label-free proteomics biomarker multiple reaction monitoring Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/d1f6d8850f3e45c4a80647f65242f9cb
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spelling	oai:doaj.org-article:d1f6d8850f3e45c4a80647f65242f9cb2021-12-01T13:30:30ZProteomics Profiling to Distinguish DOCK8 Deficiency From Atopic Dermatitis2673-610110.3389/falgy.2021.774902https://doaj.org/article/d1f6d8850f3e45c4a80647f65242f9cb2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/falgy.2021.774902/fullhttps://doaj.org/toc/2673-6101Dedicator of cytokinesis 8 deficiency is an autosomal recessive primary immune deficiency disease belonging to the group of hyperimmunoglobulinemia E syndrome (HIES). The clinical phenotype of dedicator of cytokinesis 8 (DOCK8) deficiency, characterized by allergic manifestations, increased infections, and increased IgE levels, overlaps with the clinical presentation of atopic dermatitis (AD). Despite the identification of metabolomics and cytokine biomarkers, distinguishing between the two conditions remains clinically challenging. The present study used a label-free untargeted proteomics approach using liquid-chromatography mass spectrometry with network pathway analysis to identify the differentially regulated serum proteins and the associated metabolic pathways altered between the groups. Serum samples from DOCK8 (n = 10), AD (n = 9) patients and healthy control (Ctrl) groups (n = 5) were analyzed. Based on the proteomics profile, the PLS-DA score plot between the three groups showed a clear group separation and sample clustering (R2 = 0.957, Q2 = 0.732). Significantly differentially abundant proteins (p < 0.05, FC cut off 2) were identified between DOCK8-deficient and AD groups relative to Ctrl (n = 105, and n = 109) and between DOCK8-deficient and AD groups (n = 85). Venn diagram analysis revealed a differential regulation of 24 distinct proteins from among the 85 between DOCK8-deficient and AD groups, including claspin, haptoglobin-related protein, immunoglobulins, complement proteins, fibulin, and others. Receiver-operating characteristic curve (ROC) analysis identified claspin and haptoglobin-related protein, as potential biomarkers with the highest sensitivity and specificity (AUC = 1), capable of distinguishing between patients with DOCK8 deficiency and AD. Network pathway analysis between DOCK8-deficiency and AD groups revealed that the identified proteins centered around the dysregulation of ERK1/2 signaling pathway. Herein, proteomic profiling of DOCK8-deficiency and AD groups was carried out to determine alterations in the proteomic profiles and identify a panel of the potential proteomics biomarker with possible diagnostic applications. Distinguishing between DOCK8-deficiency and AD will help in the early initiation of treatment and preventing complications.Minnie JacobAfshan MasoodZakiya ShinwariMai Abdel JabbarHamoud Al-MousaRand ArnaoutBandar AlSaudMajed DasoukiAyodele A. AlaiyaAnas M. Abdel RahmanAnas M. Abdel RahmanAnas M. Abdel RahmanFrontiers Media S.A.articleatopic dermatitisdedicator of cytokinesis (DOCK8)hyper IgE syndrome (HIES)label-free proteomicsbiomarkermultiple reaction monitoringImmunologic diseases. AllergyRC581-607ENFrontiers in Allergy, Vol 2 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	atopic dermatitis dedicator of cytokinesis (DOCK8) hyper IgE syndrome (HIES) label-free proteomics biomarker multiple reaction monitoring Immunologic diseases. Allergy RC581-607
spellingShingle	atopic dermatitis dedicator of cytokinesis (DOCK8) hyper IgE syndrome (HIES) label-free proteomics biomarker multiple reaction monitoring Immunologic diseases. Allergy RC581-607 Minnie Jacob Afshan Masood Zakiya Shinwari Mai Abdel Jabbar Hamoud Al-Mousa Rand Arnaout Bandar AlSaud Majed Dasouki Ayodele A. Alaiya Anas M. Abdel Rahman Anas M. Abdel Rahman Anas M. Abdel Rahman Proteomics Profiling to Distinguish DOCK8 Deficiency From Atopic Dermatitis
description	Dedicator of cytokinesis 8 deficiency is an autosomal recessive primary immune deficiency disease belonging to the group of hyperimmunoglobulinemia E syndrome (HIES). The clinical phenotype of dedicator of cytokinesis 8 (DOCK8) deficiency, characterized by allergic manifestations, increased infections, and increased IgE levels, overlaps with the clinical presentation of atopic dermatitis (AD). Despite the identification of metabolomics and cytokine biomarkers, distinguishing between the two conditions remains clinically challenging. The present study used a label-free untargeted proteomics approach using liquid-chromatography mass spectrometry with network pathway analysis to identify the differentially regulated serum proteins and the associated metabolic pathways altered between the groups. Serum samples from DOCK8 (n = 10), AD (n = 9) patients and healthy control (Ctrl) groups (n = 5) were analyzed. Based on the proteomics profile, the PLS-DA score plot between the three groups showed a clear group separation and sample clustering (R2 = 0.957, Q2 = 0.732). Significantly differentially abundant proteins (p < 0.05, FC cut off 2) were identified between DOCK8-deficient and AD groups relative to Ctrl (n = 105, and n = 109) and between DOCK8-deficient and AD groups (n = 85). Venn diagram analysis revealed a differential regulation of 24 distinct proteins from among the 85 between DOCK8-deficient and AD groups, including claspin, haptoglobin-related protein, immunoglobulins, complement proteins, fibulin, and others. Receiver-operating characteristic curve (ROC) analysis identified claspin and haptoglobin-related protein, as potential biomarkers with the highest sensitivity and specificity (AUC = 1), capable of distinguishing between patients with DOCK8 deficiency and AD. Network pathway analysis between DOCK8-deficiency and AD groups revealed that the identified proteins centered around the dysregulation of ERK1/2 signaling pathway. Herein, proteomic profiling of DOCK8-deficiency and AD groups was carried out to determine alterations in the proteomic profiles and identify a panel of the potential proteomics biomarker with possible diagnostic applications. Distinguishing between DOCK8-deficiency and AD will help in the early initiation of treatment and preventing complications.
format	article
author	Minnie Jacob Afshan Masood Zakiya Shinwari Mai Abdel Jabbar Hamoud Al-Mousa Rand Arnaout Bandar AlSaud Majed Dasouki Ayodele A. Alaiya Anas M. Abdel Rahman Anas M. Abdel Rahman Anas M. Abdel Rahman
author_facet	Minnie Jacob Afshan Masood Zakiya Shinwari Mai Abdel Jabbar Hamoud Al-Mousa Rand Arnaout Bandar AlSaud Majed Dasouki Ayodele A. Alaiya Anas M. Abdel Rahman Anas M. Abdel Rahman Anas M. Abdel Rahman
author_sort	Minnie Jacob
title	Proteomics Profiling to Distinguish DOCK8 Deficiency From Atopic Dermatitis
title_short	Proteomics Profiling to Distinguish DOCK8 Deficiency From Atopic Dermatitis
title_full	Proteomics Profiling to Distinguish DOCK8 Deficiency From Atopic Dermatitis
title_fullStr	Proteomics Profiling to Distinguish DOCK8 Deficiency From Atopic Dermatitis
title_full_unstemmed	Proteomics Profiling to Distinguish DOCK8 Deficiency From Atopic Dermatitis
title_sort	proteomics profiling to distinguish dock8 deficiency from atopic dermatitis
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/d1f6d8850f3e45c4a80647f65242f9cb
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Proteomics Profiling to Distinguish DOCK8 Deficiency From Atopic Dermatitis

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