Department of Clinical and Experimental Medicine, Endocrinology Unit I, University of Pisa and University Hospital of Pisa, Pisa, Italy.
Department of Surgical, Medical and Molecular Pathology, Pathology Unit, University of Pisa and University Hospital of Pisa, Pisa, Italy.
JAMA Ophthalmol. 2018 Jun 1;136(6):613-619. doi: 10.1001/jamaophthalmol.2018.0806.
Graves orbitopathy (GO) responds to immunosuppressive treatments when clinically active but poorly when inactive. In other autoimmune diseases, response has been ascribed to a reduction in lymphocytes infiltrating the target organ. It is not known whether active vs inactive GO differs in this regard, which would help in understanding the link between GO immunologic features and clinical behavior.
To investigate the association between orbital lymphocytic infiltrate and GO clinical features.
DESIGN, SETTING, AND PARTICIPANTS: A cohort study aimed at assessing the extent and immunohistochemical phenotype of orbital lymphocytes and associating it with the ophthalmologic features of GO, especially its clinical activity score (CAS), was conducted at a tertiary referral center. Twenty consecutive patients with GO who underwent orbital decompression were included. The study was conducted from January 1 to May 31, 2017.
Orbital tissue histology and immunohistochemistry testing as well as ophthalmologic evaluation.
Association between CAS and orbital lymphocytes, analyzed as total number of lymphocytes and main lymphoid subsets.
The patient population included 8 men and 12 women, all of white race, with a mean (SD) age of 46 (13) years. With an established cutoff value of 300 lymphoid cells per tissue sample, lymphocytes above this value were found in orbital tissues of 9 of 20 patients (45%), often organized into distinct foci. The lymphocytes comprised a mixture of T (CD3-positive) and B (CD20-positive) cells, suggesting a mature, polyclonal autoimmune response. In a simple linear regression model, the total number of lymphocytes, as well as the number of CD3- and CD20-positive subsets, correlated with CAS (R = 0.63; 95% CI, 0.27-0.84; P = .003; R = 0.59; 95% CI, 0.20-0.82; P = .006; and R = 0.65; 95% CI, 0.30-0.85; P = .002, respectively). In a multiple linear regression model, lymphocytes maintained their effect on CAS when adjusted for 2 additional variables that were correlated with CAS-smoking and GO duration-highlighting even more the important role of orbital lymphocytes in affecting CAS (total number: R = 0.58; 95% CI, 0.18-0.82; P = .01; CD3-positive: R = 0.58; 95% CI, 0.17-0.82; P = .01; and CD20-positive: R = 0.59; 95% CI, 0.19-0.83; P = .01).
This study shows a correlation between T and B lymphocytes infiltrating orbital tissues and the activity of GO, possibly enhancing our understanding of the association between GO immunologic features and clinical expression.
Graves 眼病（GO）在临床活动时对免疫抑制治疗有反应，但在不活动时反应不佳。在其他自身免疫性疾病中，反应归因于浸润靶器官的淋巴细胞减少。目前尚不清楚活动性与非活动性 GO 在这方面是否存在差异，这有助于了解 GO 免疫特征与临床行为之间的联系。
研究眶内淋巴细胞浸润与 GO 临床特征之间的关系。
设计、地点和参与者： 本队列研究旨在评估 GO 患者眼眶淋巴细胞的程度和免疫组织化学表型，并将其与 GO 的眼科特征相关联，特别是其临床活动评分（CAS），在一家三级转诊中心进行。纳入了 20 名连续接受眼眶减压术的 GO 患者。研究于 2017 年 1 月 1 日至 5 月 31 日进行。
眶组织组织学和免疫组织化学检测以及眼科评估。
CAS 与眶淋巴细胞的关联，分析为淋巴细胞总数和主要淋巴细胞亚群。
患者人群包括 8 名男性和 12 名女性，均为白人，平均（SD）年龄为 46（13）岁。在建立了 300 个淋巴细胞/组织样本的截断值后，发现 20 名患者中有 9 名（45%）的眶组织中有淋巴细胞超过此值，通常形成明显的焦点。淋巴细胞由 T（CD3 阳性）和 B（CD20 阳性）细胞组成，提示成熟的多克隆自身免疫反应。在简单线性回归模型中，淋巴细胞总数以及 CD3-和 CD20-阳性亚群与 CAS 相关（R=0.63；95%CI，0.27-0.84；P=0.003；R=0.59；95%CI，0.20-0.82；P=0.006；R=0.65；95%CI，0.30-0.85；P=0.002，分别）。在多元线性回归模型中，当调整与 CAS 相关的 2 个额外变量（吸烟和 GO 持续时间）时，淋巴细胞仍然对 CAS 有影响-这突出了眶淋巴细胞在影响 CAS 方面的重要作用（总数：R=0.58；95%CI，0.18-0.82；P=0.01；CD3 阳性：R=0.58；95%CI，0.17-0.82；P=0.01；和 CD20 阳性：R=0.59；95%CI，0.19-0.83；P=0.01）。
本研究显示眶组织中 T 和 B 淋巴细胞浸润与 GO 的活动度相关，可能增强了我们对 GO 免疫特征与临床表达之间关系的理解。
