Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Hospital de Santa Maria, Centro Hospitalar Lisboa Norte and Lisbon Academic Medical Center, Lisbon, Portugal.
Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal, and Instituto Gulbenkian de Ciência, Oeiras, Portugal.
Arthritis Rheumatol. 2018 May;70(5):774-784. doi: 10.1002/art.40424. Epub 2018 Mar 25.
To investigate whether the balance of blood follicular helper T (Tfh) cells and T follicular regulatory (Tfr) cells can provide information about ectopic lymphoid neogenesis and disease activity in primary Sjögren's syndrome (SS).
We prospectively recruited 56 patients clinically suspected of having SS. Sixteen of these patients subsequently fulfilled the American-European Consensus Group criteria for SS and were compared to 16 patients with non-SS sicca syndrome. Paired blood and minor salivary gland (MSG) biopsy samples were analyzed to study Tfr cells and subsets of Tfh cells in both compartments.
Patients with primary SS had normal Tfh cell counts in peripheral blood; however, activated programmed death 1-positive (PD-1+) inducible costimulator-positive (ICOS+) Tfh cells in peripheral blood were strongly associated with disease activity assessed by the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (r = 0.8547, P = 0.0008). Conversely, the blood Tfr cell:Tfh cell ratio indicated ectopic lymphoid structure formation in MSGs, being strongly associated with B cell, CD4+ T cell, and PD-1+ICOS+ T cell infiltration in MSGs, and was especially increased in patients with focal sialadenitis. Further analysis showed that the blood Tfr cell:Tfh cell ratio allowed discrimination between SS patients and healthy donors with excellent accuracy and was a strong predictor of SS diagnosis (odds ratio [OR] 12.96, P = 0.028) and the presence of focal sialadenitis (OR 10, P = 0.022) in patients investigated for sicca symptoms, thus highlighting the potential clinical value of this marker.
The blood Tfr cell:Tfh cell ratio and PD-1+ICOS+ Tfh cells constitute potential novel biomarkers for different features of primary SS. While the blood Tfr cell:Tfh cell ratio is associated with ectopic lymphoid neogenesis, activated Tfh cells indicate disease activity.
探讨滤泡辅助性 T（Tfh）细胞与滤泡调节性 T（Tfr）细胞的平衡是否能为原发性干燥综合征（SS）的异位淋巴样新生和疾病活动提供信息。
我们前瞻性地招募了 56 名临床疑似患有 SS 的患者。其中 16 名患者随后符合美国欧洲共识组 SS 标准，并与 16 名非 SS 干燥综合征患者进行了比较。对配对的血液和小唾液腺（MSG）活检样本进行分析，以研究两个部位的 Tfr 细胞和 Tfh 细胞亚群。
原发性 SS 患者外周血中 Tfh 细胞计数正常；然而，外周血中激活的程序性死亡 1 阳性（PD-1+）诱导协同刺激分子阳性（ICOS+）Tfh 细胞与欧洲抗风湿病联盟干燥综合征疾病活动指数（EULAR Sjögren's Syndrome Disease Activity Index，ESSDAI）评估的疾病活动强烈相关（r = 0.8547，P = 0.0008）。相反，血液 Tfr 细胞：Tfh 细胞比值提示 MSG 中异位淋巴样结构形成，与 MSG 中 B 细胞、CD4+T 细胞和 PD-1+ICOS+T 细胞浸润强烈相关，且在局灶性唾液腺炎患者中明显增加。进一步分析表明，血液 Tfr 细胞：Tfh 细胞比值能够区分 SS 患者和健康供者，且具有良好的准确性，是 SS 诊断（比值比[OR]12.96，P = 0.028）和局灶性唾液腺炎（OR 10，P = 0.022）的强有力预测因子，提示该标志物具有潜在的临床价值。
血液 Tfr 细胞：Tfh 细胞比值和 PD-1+ICOS+Tfh 细胞构成原发性 SS 不同特征的潜在新型生物标志物。血液 Tfr 细胞：Tfh 细胞比值与异位淋巴样新生相关，而激活的 Tfh 细胞则提示疾病活动。
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