دورية أكاديمية
أعرض في EDS

Targeted Proteomics Reveals Inflammatory Pathways that Classify Immune Dysregulation in Common Variable Immunodeficiency.

التفاصيل البيبلوغرافية
العنوان: Targeted Proteomics Reveals Inflammatory Pathways that Classify Immune Dysregulation in Common Variable Immunodeficiency.
المؤلفون: Berbers RM; Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht and Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands., Drylewicz J; Center for Translational Immunology, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands., Ellerbroek PM; Department of Internal Medicine and Infectious Diseases, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands., van Montfrans JM; Department of Pediatric Immunology and Infectious Diseases, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands., Dalm VASH; Department of Internal Medicine, Division of Clinical Immunology; Department of Immunology; Academic Center for Rare Immunological Diseases (RIDC), Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands., van Hagen PM; Department of Internal Medicine, Division of Clinical Immunology; Department of Immunology; Academic Center for Rare Immunological Diseases (RIDC), Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands., Keller B; Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., Warnatz K; Department of Rheumatology and Clinical Immunology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.; Center for Chronic Immunodeficiency (CCI), Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany., van de Ven A; Departments of Internal Medicine and Allergology, Rheumatology and Clinical Immunology, University Medical Center Groningen, Groningen, The Netherlands., van Laar JM; Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht and Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands., Nierkens S; Center for Translational Immunology, University Medical Center Utrecht and Utrecht University, Utrecht, The Netherlands., Leavis HL; Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht and Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. h.leavis@umcutrecht.nl.
المصدر: Journal of clinical immunology [J Clin Immunol] 2021 Feb; Vol. 41 (2), pp. 362-373. Date of Electronic Publication: 2020 Nov 15.
نوع المنشور: Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Springer Country of Publication: Netherlands NLM ID: 8102137 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-2592 (Electronic) Linking ISSN: 02719142 NLM ISO Abbreviation: J Clin Immunol Subsets: MEDLINE
أسماء مطبوعة: Publication: Amsterdam : Springer
Original Publication: New York : Plenum, c1981-
مواضيع طبية MeSH: Common Variable Immunodeficiency/*immunology , Common Variable Immunodeficiency/*metabolism , Inflammation/*immunology , Inflammation/*metabolism , Signal Transduction/*immunology, Adult ; Biomarkers/metabolism ; Chemokines/immunology ; Chemokines/metabolism ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; Proteomics/methods ; Th1 Cells/immunology ; Th1 Cells/metabolism ; Th17 Cells/immunology ; Th17 Cells/metabolism
مستخلص: Patients with common variable immunodeficiency (CVID) can develop immune dysregulation complications such as autoimmunity, lymphoproliferation, enteritis, and malignancy, which cause significant morbidity and mortality. We aimed to (i) assess the potential of serum proteomics in stratifying patients with immune dysregulation using two independent cohorts and (ii) identify cytokine and chemokine signaling pathways that underlie immune dysregulation in CVID. A panel of 180 markers was measured in two multicenter CVID cohorts using Olink Protein Extension Assay technology. A classification algorithm was trained to distinguish CVID with immune dysregulation (CVIDid, n = 14) from CVID with infections only (CVIDio, n = 16) in the training cohort, and validated on a second testing cohort (CVIDid n = 23, CVIDio n = 24). Differential expression in both cohorts was used to determine relevant signaling pathways. An elastic net classifier using MILR1, LILRB4, IL10, IL12RB1, and CD83 could discriminate between CVIDid and CVIDio patients with a sensitivity of 0.83, specificity of 0.75, and area under the curve of 0.73 in an independent testing cohort. Activated pathways (fold change > 1.5, FDR-adjusted p < 0.05) in CVIDid included Th1 and Th17-associated signaling, as well as IL10 and other immune regulatory markers (LAG3, TNFRSF9, CD83). Targeted serum proteomics provided an accurate and reproducible tool to discriminate between patients with CVIDid and CVIDio. Cytokine profiles provided insight into activation of Th1 and Th17 pathways and indicate a possible role for chronic inflammation and exhaustion in immune dysregulation. These findings serve as a first step towards the development of biomarkers for immune dysregulation in CVID.
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فهرسة مساهمة: Keywords: Biomarkers; Common variable immunodeficiency (CVID); Cytokines; Immune dysregulation; Prediction; Primary immunodeficiency
المشرفين على المادة: 0 (Biomarkers)
0 (Chemokines)
تواريخ الأحداث: Date Created: 20201115 Date Completed: 20220118 Latest Revision: 20220118
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC7858548
DOI: 10.1007/s10875-020-00908-1
PMID: 33190167
قاعدة البيانات: MEDLINE
الوصف
تدمد:1573-2592
DOI:10.1007/s10875-020-00908-1