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Proteomics Profiling to Distinguish DOCK8 Deficiency From Atopic Dermatitis
Minnie Jacob1, Afshan Masood2, Zakiya Shinwari3
1Metabolomics Section, Department of Clinical Genomics, Center for Genomics Medicine, King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia.
Frontiers in Allergy
|April 7, 2022
Summary
Dedicator of cytokinesis 8 (DOCK8) deficiency and atopic dermatitis (AD) share symptoms, but proteomics analysis identified distinct serum protein profiles. Claspin and haptoglobin-related protein show promise as biomarkers for differentiating these conditions.
Area of Science:
- Immunology
- Proteomics
- Biochemistry
Background:
- Dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal recessive primary immune deficiency disease.
- DOCK8 deficiency shares clinical features with atopic dermatitis (AD), including allergic manifestations, recurrent infections, and elevated IgE levels, making clinical differentiation challenging.
- Existing metabolomic and cytokine biomarkers have not sufficiently resolved diagnostic ambiguity between DOCK8 deficiency and AD.
Purpose of the Study:
- To differentiate between DOCK8 deficiency and AD using label-free untargeted proteomics.
- To identify differentially regulated serum proteins and associated metabolic pathways between DOCK8 deficiency, AD, and healthy controls.
- To discover novel protein biomarkers for accurate diagnosis of DOCK8 deficiency and AD.
Main Methods:
- Serum samples from patients with DOCK8 deficiency (n=10), AD (n=9), and healthy controls (n=5) were analyzed using liquid chromatography-mass spectrometry (LC-MS).
- Label-free untargeted proteomics and network pathway analysis were employed to identify differentially abundant proteins and altered pathways.
- Statistical analyses including Partial Least Squares Discriminant Analysis (PLS-DA), Venn diagrams, and Receiver Operating Characteristic (ROC) curve analysis were performed.
Main Results:
- Proteomics profiling demonstrated clear separation and clustering of DOCK8 deficiency, AD, and control groups (R2=0.957, Q2=0.732).
- A total of 85 differentially abundant proteins were identified between DOCK8 deficiency and AD groups, with 24 distinct proteins identified via Venn diagram analysis.
- Claspin and haptoglobin-related protein were identified as potential diagnostic biomarkers with high sensitivity and specificity (AUC=1) for distinguishing DOCK8 deficiency from AD.
- Network pathway analysis indicated dysregulation of the ERK1/2 signaling pathway in DOCK8 deficiency compared to AD.
Conclusions:
- Proteomic profiling offers a robust method for distinguishing DOCK8 deficiency from AD.
- Claspin and haptoglobin-related protein represent promising novel biomarkers for the differential diagnosis of DOCK8 deficiency and AD.
- Accurate differentiation between DOCK8 deficiency and AD is crucial for timely treatment initiation and prevention of complications.
