{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T17:51:17Z","timestamp":1790704277703,"version":"4.1.0"},"reference-count":54,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T00:00:00Z","timestamp":1573516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Bi-allelic mutations in the dedicator of cytokinesis 8 (DOCK8) are responsible for a rare autosomal recessive primary combined immunodeficiency syndrome, characterized by atopic dermatitis, elevated serum Immunoglobulin E (IgE) levels, recurrent severe cutaneous viral infections, autoimmunity, and predisposition to malignancy. The molecular link between DOCK8 deficiency and atopic skin inflammation remains unknown. Severe atopic dermatitis (AD) and DOCK8 deficiency share some clinical symptoms, including eczema, eosinophilia, and increased serum IgE levels. Increased serum IgE levels are characteristic of, but not specific to allergic diseases. Herein, we aimed to study the metabolomic profiles of DOCK8-deficient and AD patients for potential disease-specific biomarkers using chemical isotope labeling liquid chromatography-mass spectrometry (CIL LC-MS). Serum samples were collected from DOCK8-deficient (n = 10) and AD (n = 9) patients. Metabolomics profiling using CIL LC-MS was performed on patient samples and compared to unrelated healthy controls (n = 33). Seven metabolites were positively identified, distinguishing DOCK8-deficient from AD patients. Aspartic acid and 3-hydroxyanthranillic acid (3HAA, a tryptophan degradation pathway intermediate) were up-regulated in DOCK8 deficiency, whereas hypotaurine, leucyl-phenylalanine, glycyl-phenylalanine, and guanosine were down-regulated. Hypotaurine, 3-hydroxyanthranillic acid, and glycyl-phenylalanine were identified as potential biomarkers specific to DOCK8 deficiency. Aspartate availability has been recently implicated as a limiting metabolite for tumour growth and 3HAA; furthermore, other tryptophan metabolism pathway-related molecules have been considered as potential novel targets for cancer therapy. Taken together, perturbations in tryptophan degradation and increased availability of aspartate suggest a link of DOCK8 deficiency to oncogenesis. Additionally, perturbations in taurine and dipeptides metabolism suggest altered antixidation and cell signaling states in DOCK8 deficiency. Further studies examining the mechanisms underlying these observations are necessary.<\/jats:p>","DOI":"10.3390\/metabo9110274","type":"journal-article","created":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T04:07:07Z","timestamp":1573531627000},"page":"274","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Metabolomics Distinguishes DOCK8 Deficiency from Atopic Dermatitis: Towards a Biomarker Discovery"],"prefix":"10.3390","volume":"9","author":[{"given":"Minnie","family":"Jacob","sequence":"first","affiliation":[{"name":"Department of Genetics, King Faisal Specialist Hospital and Research Center (KFSH-RC), Riyadh 11211, Saudi Arabia"},{"name":"Australian Institute of Tropical Health and Medicine, James Cook University, Townsville QLD 4814, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyun","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1026-845X","authenticated-orcid":false,"given":"Xian","family":"Luo","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamoud","family":"Al-Mousa","sequence":"additional","affiliation":[{"name":"Section of Pediatric Allergy and Immunology, Department of Pediatrics, King Faisal Specialist Hospital &amp; Research Centre (KFSH-RC), Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rand","family":"Arnaout","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bandar","family":"Al-Saud","sequence":"additional","affiliation":[{"name":"Section of Pediatric Allergy and Immunology, Department of Pediatrics, King Faisal Specialist Hospital &amp; Research Centre (KFSH-RC), Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"L. Lopata","sequence":"additional","affiliation":[{"name":"Australian Institute of Tropical Health and Medicine, James Cook University, Townsville QLD 4814, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9347-2108","authenticated-orcid":false,"given":"Liang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Chemistry, University of Alberta, Edmonton, AB T6G 2R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majed","family":"Dasouki","sequence":"additional","affiliation":[{"name":"Department of Genetics, King Faisal Specialist Hospital and Research Center (KFSH-RC), Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9527-9424","authenticated-orcid":false,"given":"Anas","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Genetics, King Faisal Specialist Hospital and Research Center (KFSH-RC), Riyadh 11211, Saudi Arabia"},{"name":"College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"},{"name":"Department of Chemistry, Memorial University of Newfoundland, St. John\u2019s, NL A1B 3X7, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0022-3476(03)00449-9","article-title":"Autosomal recessive hyperimmunoglobulin E syndrome: A distinct disease entity","volume":"144","author":"Renner","year":"2004","journal-title":"J. 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