loading page

Proteomics profiling to distinguish DOCK8 deficiency from atopic dermatitis
  • +7
  • Minnie Jacob,
  • Afshan Masood,
  • Zakia Shinwari ,
  • Mai Abdel Jabbar,
  • Hamoud Al-Mousa,
  • Bander Alsaud,
  • Rand Arnout,
  • Majed Dasouki,
  • Ayodele Alaiya,
  • Anas Abdel Rahman
Minnie Jacob
King Faisal Specialist Hospital and Research Center
Author Profile
Afshan Masood
King Saud University
Author Profile
Zakia Shinwari
King Faisal Specialist Hospital and Research Center
Author Profile
Mai Abdel Jabbar
King Faisal Specialist Hospital and Research Center
Author Profile
Hamoud Al-Mousa
King Faisal Specialist Hospital and Research Center
Author Profile
Bander Alsaud
King Faisal Specialist Hospital and Research Center
Author Profile
Rand Arnout
King Faisal Specialist Hospital and Research Center
Author Profile
Majed Dasouki
King Faisal Specialist Hospital and Research Center
Author Profile
Ayodele Alaiya
King Faisal Specialist Hospital and Research Centre
Author Profile
Anas Abdel Rahman
King Faisal Specialist Hospital and Research Center

Corresponding Author:[email protected]

Author Profile

Abstract

Background: DOCK8 deficiency is an autosomal recessive form of hyperimmunoglobulinemia E syndrome (HIES). Severe atopic dermatitis (AD) shares with DOCK8 deficiency some clinical symptoms, including eczema, eosinophilia, and increased serum IgE levels. The deficiency of DOCK8 protein is potentially a life-threatening autosomal recessive HIES and only curable with bone marrow transplantation. Despite identified metabolomics and cytokine biomarkers, novel proteomics biomarkers need to be identified, as the connecting networks are critical to our understanding of this disease. Hence we performed serum proteomic profiling using LC-MSE. Method: Label-free untargeted proteomics analysis was used to identify potentially reliable, sensitive, and specific protein biomarkers in serum collected from DOCK8 (n=10), AD (n=9) patients compared to healthy control groups (n=5). Results: From a total of 275 quantifiable proteins, binary comparisons between AD vs. Ctrl, DOCK8 vs. Ctrl, and DOCK8 vs. AD revealed 109,105 and 85 dysregulated proteins, respectively. 24 of the 85 proteins were specific potential biomarkers among the DOCK8 and AD groups. The sensitivity and specificity of some proteins, including Claspin, Immunoglobulin kappa, and heavy complement components as potential biomarkers to distinguish between DOCK8 and AD patients, were evaluated using the receiver operating characteristic curve. DOCK8 deficiency and AD groups’ profiling revealed a shared role of ERK1/2 among the commonly dysregulated proteins. Conclusion: Herein, we have identified potential proteomics biomarkers and profile to distinguish between DOCK8 and AD, with possible diagnostic and therapeutic applications to help create effective interventions for managing these diseases. Further studies to confirm these associations in prospective cohorts are warranted