T cell responses to peptides of Goodpasture autoantigen in patients with anti-glomerular basement membrane disease
T cell responses to peptides of Goodpasture autoantigen in patients with anti-glomerular basement membrane disease
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抗肾小球基底膜疾病患者的 T 细胞对 Goodpasture 自身抗原肽的反应
DOI：
10.1111/nep.13020
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发表时间：
2018
期刊：
影响因子：
2.5
通讯作者：
Zhao Ming-Hui
中科院分区：
文献类型：
--
作者：
Hu Shui-Yi;Jia Xiao-Yu;Gu Qiu-Hua;Yu Chong-Yan;Cheng Xu-Yang;Jin Qi-Zhuang;Zhou Fu-De;Cui Zhao;Zhao Ming-Hui
细胞介导的自身免疫，尤其是自身反应性T细胞，在抗肾小球膜（GBM）疾病的发生中起着至关重要的作用。Goodpasture自身抗原上T细胞的表位尚未完全确定。本研究对抗GBM患者的T细胞表位进行了研究，目的是确定T细胞表位及其临床意义。方法采集13例抗GBM患者外周血单个核细胞（PBMC）。合成了24个重叠的线性肽，覆盖了人α3(IV)NC1的整个序列。增殖试验检测PBMC对各肽的反应。进一步分析其与临床特征的关系。结果所有患者外周血单个核细胞对α3(IV)NC1均有增殖反应。在半数以上的患者中，α3(IV) NC1127-148 (P14)（69.2%）、α3(IV) NC1159-178（77.8%）、α3(IV) NC1179-198（55.6%）、α3(IV) NC1189-208 (P19)（75.0%）和α3(IV) NC1141-154（57.1%）具有刺激作用。与健康对照组相比，患者对P14和P19的认知度较高（69.2%vs.0.0%，P= 0.011; 75.0%vs.0.0%,P =0.021）。结论在人抗GBM疾病中检测到t细胞向线性表位增殖。α3127 - 148是T细胞和B细胞的互表位，提示其在表位扩散过程中的初始作用。
AimCell‐mediated autoimmunity, especially autoreactive T cells, is crucial in the initiation of anti‐glomerular membrane (GBM) disease. Epitopes for T cells on Goodpasture autoantigen are not fully defined. This study investigated T cell epitopes in anti‐GBM patients, aiming to identify the epitopes and their clinical significance.MethodsPeripheral blood mononuclear cells (PBMC) were collected from 13 patients with anti‐GBM disease. Twenty‐four overlapping linear peptides were synthesized covering the whole sequence of human α3(IV)NC1. PBMC response to each peptide was detected by proliferation assay. Their associations with clinical features were further analyzed.ResultsPeripheral blood mononuclear cells proliferative responses to linear peptides on α3(IV)NC1 could be detected in all patients. Five major epitopes were identified as stimulatory in over half of the patients: α3(IV)NC1127–148(P14) (69.2%), α3(IV)NC1159–178(77.8%), α3(IV)NC1179–198(55.6%), α3(IV)NC1189–208(P19) (75.0%) and α3(IV)NC1141–154(57.1%). P14 and P19 were highly recognized in patients comparing with healthy controls (69.2%vs.0.0%,P= 0.011; 75.0%vs.0.0%,P =0.021, respectively).ConclusionT cell proliferation to linear epitopes was detected in human anti‐GBM disease. α3127–148was a mutual T and B cell epitope, implying its initial role in epitope spreading process.