التفاصيل البيبلوغرافية
| العنوان: |
Technical Validation and Utility of an HLA Class II Tetramer Assay for Type 1 Diabetes: A Multicenter Study. |
| المؤلفون: |
Ettinger, Ruth A, Buitinga, Mijke, Vandamme, Céline, Afonso, Georgia, Gomez, Rebecca, Arribas-Layton, David, Bissenova, Samal, Speake, Cate, Reijonen, Helena, Kinnunen, Tuure, Overbergh, Lut, Mallone, Roberto, Kwok, William W, James, Eddie A |
| المصدر: |
Journal of Clinical Endocrinology & Metabolism; Jan2024, Vol. 109 Issue 1, p183-196, 14p |
| مصطلحات موضوعية: |
TYPE 1 diabetes, HLA class II antigens, PHENOTYPES |
| مستخلص: |
Context Validated assays to measure autoantigen-specific T-cell frequency and phenotypes are needed for assessing the risk of developing diabetes, monitoring disease progression, evaluating responses to treatment, and personalizing antigen-based therapies. Objective Toward this end, we performed a technical validation of a tetramer assay for HLA-DRA-DRB1*04:01, a class II allele that is strongly associated with susceptibility to type 1 diabetes (T1D). Methods HLA-DRA-DRB1*04:01-restricted T cells specific for immunodominant epitopes from islet cell antigens GAD65, IGRP, preproinsulin, and ZnT8, and a reference influenza epitope, were enumerated and phenotyped in a single staining tube with a tetramer assay. Single and multicenter testing was performed, using a clone-spiked specimen and replicate samples from T1D patients, with a target coefficient of variation (CV) less than 30%. The same assay was applied to an exploratory cross-sectional sample set with 24 T1D patients to evaluate the utility of the assay. Results Influenza-specific T-cell measurements had mean CVs of 6% for the clone-spiked specimen and 11% for T1D samples in single-center testing, and 20% and 31%, respectively, for multicenter testing. Islet-specific T-cell measurements in these same samples had mean CVs of 14% and 23% for single-center and 23% and 41% for multicenter testing. The cross-sectional study identified relationships between T-cell frequencies and phenotype and disease duration, sex, and autoantibodies. A large fraction of the islet-specific T cells exhibited a naive phenotype. Conclusion Our results demonstrate that the assay is reproducible and useful to characterize islet-specific T cells and identify correlations between T-cell measures and clinical traits. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
