Côté-Bigras Sarah, Dionne Audrey, Asselin-Mullen Patrick, Leblicq Coralie, Rottembourg Diane
Faculty of Medicine, University Hospital Sherbrooke, Sherbrooke, QC, Canada.
Clin Endocrinol (Oxf). 2014 Feb;80(2):296-300. doi: 10.1111/cen.12257. Epub 2013 Jun 27.
While thyrotrophin receptor (TSHR) is recognized as the main autoantigen in Graves' disease (GD), the actual antigen specificity of T cells that infiltrate the thyroid and the orbit is unknown. Identifying T cell responses to TSHR peptides has been difficult in the past due to the low frequency of autoreactive T cells and to the diversity of the putative epitopes identified by proliferation assays.
We used the interferon-gamma ELISPOT assay to identify T cell reactivity to TSHR peptides in patients with GD. Peripheral blood T cells were exposed in vitro to four pools of 10 overlapping TSHR peptides.
T cells from 11 of 31 (35%) patients with GD and 1 of 22 (4%) healthy controls reacted to at least one peptide pool (P = 0·009). Mean time since diagnosis was 3·2 years in responder patients and 5·6 years in nonresponders (P = 0·07). In two patients, T cell reactivity was observed shortly after radioiodine treatment and not thereafter.
Our findings demonstrate that the ELISPOT assay is effective to test T cell reactivity in patients with GD and that patients with GD have significantly more interferon-gamma responses towards TSHR peptides than controls. The data suggest that screening for T cell responses in patients with GD might be more efficient in recent-onset disease or after radioiodine treatment.
虽然促甲状腺激素受体（TSHR）被认为是格雷夫斯病（GD）的主要自身抗原，但浸润甲状腺和眼眶的T细胞的实际抗原特异性尚不清楚。由于自身反应性T细胞频率低以及增殖试验确定的假定表位的多样性，过去识别T细胞对TSHR肽的反应一直很困难。
我们使用干扰素-γ酶联免疫斑点分析（ELISPOT分析）来识别GD患者中T细胞对TSHR肽的反应性。将外周血T细胞在体外暴露于4组由10个重叠TSHR肽组成的肽库。
31例GD患者中的11例（35%）和22例健康对照中的1例（4%）的T细胞对至少一个肽库有反应（P = 0·009）。有反应的患者自诊断以来的平均时间为3·2年，无反应的患者为5·6年（P = 0·07）。在2例患者中，在放射性碘治疗后不久观察到T细胞反应性，之后未观察到。
我们的研究结果表明，ELISPOT分析可有效检测GD患者的T细胞反应性，且GD患者对TSHR肽的干扰素-γ反应明显多于对照组。数据表明，在GD患者中筛查T细胞反应在疾病近期发病或放射性碘治疗后可能更有效。
