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原发性干燥综合征和干燥综合征患者的记忆 B 细胞与临床和免疫特征的相关性。

Association between memory B-cells and clinical and immunological features of primary Sjögren's syndrome and Sicca patients.

机构信息

CEDOC, Chronic Diseases Research Center, Immunology, NOVA Medical School|FCM, Universidade Nova de Lisboa, Lisbon, Portugal.

Departement of Rheumatology, Instituto Português de Reumatologia, Lisbon, Portugal.

出版信息

Rheumatol Int. 2018 Jun;38(6):1063-1073. doi: 10.1007/s00296-018-4018-0. Epub 2018 Apr 6.

Abstract

B-cells play a pivotal role in primary Sjögren's syndrome (pSS) pathogenesis. We aim to (1) evaluate the distribution of B-lymphocyte subpopulations in pSS and Sicca patients, (2) establish cut-off points that discriminate pSS from controls, (3) evaluate the association between memory B-cells and phenotypic features in pSS. We included 57 pSS patients, 68 Sicca and 24 healthy controls. Circulating B-cells were characterized by flow cytometry as naïve and memory subsets and classified from Bm1 to Bm5. Compared to controls, pSS patients had lower percentages (29.5 vs 44.4%) and absolute numbers (47 vs 106 cells/µl) of memory B-cells. Through ROC curves, a cut-off of ≤ 58 total memory B-cells/µl yielded a specificity of 0.88 and a sensitivity of 0.60 for pSS, and was met by 59.6% of pSS patients, 38.8% of Sicca and 12.5% of controls. A cut-off of < 23.5 Switched-memory B-cells/µl yielded a specificity of 0.88 and a sensitivity of 0.54 and was met by 54.4% of pSS patients, 37.3% of Sicca and 12.5% of controls. In pSS, lower total memory B-cells count was associated with longer disease duration (14.3 vs 8.1 years, p = 0.006) and more active disease profile, as evaluated by the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) (3.1 vs 1.4, p = 0.043). Decreased numbers of memory B-cells clearly discriminated pSS from controls and can also have prognostic value. It remains to be clarified whether Sicca patients with decreased memory B-cells represent pSS and if B-cell profiling could help in the diagnosis of pSS.

摘要

B 细胞在原发性干燥综合征 (pSS) 的发病机制中起着关键作用。我们旨在:(1) 评估 pSS 和干燥综合征患者中 B 淋巴细胞亚群的分布;(2) 确定区分 pSS 与对照的截止值;(3) 评估记忆 B 细胞与 pSS 表型特征之间的相关性。我们纳入了 57 例 pSS 患者、68 例干燥综合征患者和 24 名健康对照者。通过流式细胞术对循环 B 细胞进行特征分析,分为幼稚和记忆亚群,并从 Bm1 到 Bm5 进行分类。与对照组相比,pSS 患者的记忆 B 细胞百分比(29.5%比 44.4%)和绝对值(47 比 106 个/µl)均较低。通过 ROC 曲线,总记忆 B 细胞数≤58 个/µl 的截断值对 pSS 的特异性为 0.88,敏感性为 0.60,符合 59.6%的 pSS 患者、38.8%的干燥综合征患者和 12.5%的对照组。<23.5 个转换记忆 B 细胞/µl 的截断值对 pSS 的特异性为 0.88,敏感性为 0.54,符合 54.4%的 pSS 患者、37.3%的干燥综合征患者和 12.5%的对照组。在 pSS 中,总记忆 B 细胞计数越低与疾病持续时间更长(14.3 比 8.1 年,p=0.006)和更活跃的疾病谱相关,如欧洲抗风湿病联盟(EULAR)干燥综合征疾病活动指数(ESSDAI)评估(3.1 比 1.4,p=0.043)。记忆 B 细胞数量的减少可以明确区分 pSS 和对照组,并且可能具有预后价值。尚不清楚减少记忆 B 细胞的干燥综合征患者是否代表 pSS,以及 B 细胞分析是否有助于 pSS 的诊断。

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