دورية أكاديمية
A degranulation assay using Vγ9Vδ2 T cells for the rapid diagnosis of familial hemophagocytic syndromes.
| العنوان: | A degranulation assay using Vγ9Vδ2 T cells for the rapid diagnosis of familial hemophagocytic syndromes. |
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| المؤلفون: | Jorisch-Mühlebach O; Division of Immunology and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland., Pitts D; Division of Immunology and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland., Tinner R; Division of Immunology and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland., Teh HY; Division of Immunology and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland., Roelli C; Division of Immunology and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland., Prader S; Division of Immunology and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland., Vavassori S; Division of Immunology and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland., Pachlopnik Schmid J; Division of Immunology and Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.; Pediatric Immunology, University of Zurich, Zurich, Switzerland. |
| المصدر: | Frontiers in immunology [Front Immunol] 2024 Jun 26; Vol. 15, pp. 1391967. Date of Electronic Publication: 2024 Jun 26 (Print Publication: 2024). |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Lausanne : Frontiers Research Foundation] |
| مواضيع طبية MeSH: | Lymphohistiocytosis, Hemophagocytic*/diagnosis , Lymphohistiocytosis, Hemophagocytic*/immunology , Lymphohistiocytosis, Hemophagocytic*/genetics , Cell Degranulation* , Killer Cells, Natural*/immunology , Killer Cells, Natural*/metabolism, Humans ; Female ; Male ; Receptors, Antigen, T-Cell, gamma-delta/metabolism ; Receptors, Antigen, T-Cell, gamma-delta/genetics ; Child, Preschool ; Child ; Infant ; Adolescent ; rab27 GTP-Binding Proteins/genetics ; Membrane Proteins/genetics ; Membrane Proteins/metabolism ; Adult ; T-Lymphocytes/immunology ; Reproducibility of Results ; Lymphocyte Activation ; Sensitivity and Specificity ; Munc18 Proteins |
| مستخلص: | Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening immune disorder characterized by uncontrolled lymphocyte and macrophage activation and a subsequent cytokine storm. The timely initiation of immunosuppressive treatment is crucial for survival. Methods: Here, we harnessed Vγ9Vδ2 T cell degranulation to develop a novel functional assay for the diagnosis of HLH. We compared the novel assay with the conventional natural killer (NK) cell stimulation method in terms of efficiency, specificity, and reliability. Our analysis involved 213 samples from 182 individuals, including 23 samples from 12 patients with degranulation deficiency (10 individuals with UNC13D deficiency, 1 with STXBP2 deficiency, and 1 with RAB27A deficiency). Results: While both tests exhibited 100% sensitivity, the Vγ9Vδ2 T cell degranulation assay showed a superior specificity of 86.2% (n=70) compared to the NK cell degranulation assay, which achieved 78.9% specificity (n=213). The Vγ9Vδ2 T cell degranulation assay offered simpler technical requirements and reduced labor intensity, leading to decreased susceptibility to errors with faster processing times. Discussion: This efficiency stemmed from the sole requirement of dissolving ( E )-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) powder, contrasting with the intricate maintenance of K562 cells necessary for the NK cell degranulation assay. With its diminished susceptibility to errors, we anticipate that the assay will require fewer repetitions of analysis, rendering it particularly well-suited for testing infants. Conclusion: The Vγ9Vδ2 T cell degranulation assay is a user-friendly, efficient diagnostic tool for HLH. It offers greater specificity, reliability, and practicality than established methods. We believe that our present findings will facilitate the prompt, accurate diagnosis of HLH and thus enable rapid treatment and better patient outcomes. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Jorisch-Mühlebach, Pitts, Tinner, Teh, Roelli, Prader, Vavassori and Pachlopnik Schmid.) |
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| فهرسة مساهمة: | Keywords: HLH; HMBPP; K562; NK cell; Vγ9Vδ2 T cell; degranulation assay; gd T cell; hemophagocytic lymphohistiocytosis |
| المشرفين على المادة: | 0 (UNC13D protein, human) 0 (Receptors, Antigen, T-Cell, gamma-delta) 0 (STXBP2 protein, human) 0 (rab27 GTP-Binding Proteins) 0 (Membrane Proteins) EC 3.6.1.-. (RAB27A protein, human) 0 (Munc18 Proteins) |
| تواريخ الأحداث: | Date Created: 20240711 Date Completed: 20240711 Latest Revision: 20240712 |
| رمز التحديث: | 20240712 |
| مُعرف محوري في PubMed: | PMC11233720 |
| DOI: | 10.3389/fimmu.2024.1391967 |
| PMID: | 38989281 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1664-3224 |
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| DOI: | 10.3389/fimmu.2024.1391967 |