Proteomics Profiling to Distinguish DOCK8 Deficiency From Atopic Dermatitis

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

doi:10.3389/falgy.2021.774902

Proteomics Profiling to Distinguish DOCK8 Deficiency From Atopic Dermatitis

Front Allergy. 2021 Nov 29:2:774902. doi: 10.3389/falgy.2021.774902. eCollection 2021.

Authors

Affiliations

¹ Metabolomics Section, Department of Clinical Genomics, Center for Genomics Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
² Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia.
³ Proteomics Unit, Stem-Cell and Tissue Re-engineering Program, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
⁴ Section of Pediatric Allergy and Immunology, Department of Pediatrics, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
⁵ Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia.
⁶ Department of Chemistry, Memorial University of Newfoundland, St. John's, NL, Canada.

Abstract

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.

Keywords: atopic dermatitis; biomarker; dedicator of cytokinesis (DOCK8); hyper IgE syndrome (HIES); label-free proteomics; multiple reaction monitoring.