结节病的临床表现决定了17型T辅助细胞亚群组成和细胞因子谱的改变

N. Lazareva, I. Kudryavtsev, O. Baranova, D. Isakov, M. Serebriakova, A. A. Bazhanov, N. A. Arsentieva, N. Liubimova, T. Ses’, M. Ilkovich, A. Totolian
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引用次数: 0

摘要

免疫细胞的过度活化及其产生的细胞因子在结节病及其相关疾病的发病机制中起重要作用。结节病的免疫发病机制是由辅助性T细胞群(包括Th17亚群和相关的特征细胞因子)控制的多种细胞介导的反应所控制的。我们研究了123例结节病患者的外周血血浆样本:18%为急性病程,82%为慢性病程。对照组——健康志愿者样本(n = 43)。流式细胞术检测T细胞亚群组成。细胞因子浓度(pg/mL)采用多重分析xMAP技术(Luminex)测定。“经典”Th17水平在急性结节病和慢性结节病中显著降低:28.3%比33.3% (p = 0.046)。“双阳性”Th17 (DP Th17)水平在慢性和急性组与对照组相比显著升高:分别为31.7%和34.2%对26.2% (p < 0.001),组间无差异;“非经典”Th17.1水平仅在慢性受试者和健康受试者中显著降低:27.9%和35.9% (p < 0.001)。结节病患者cd45ra阴性Th效应记忆细胞血液中DP Th17水平的临床和实验室诊断特征:急性结节病患者与健康受试者的敏感性为82%;特异性为71%,而慢性:分别为67%和56%。结节病患者与健康人相比IL-12水平显著升高(p70)——1.3 vs 0.56, p = 0.028;IL-17A - 1.5 vs 0.43, p < 0.001;IFNγ - 4.1 vs 1.1, p < 0.001;TNFα - 21.7 vs 6.7, p < 0.001。因此,CCR6+ Th17和DP Th17亚群以及相关的特征细胞因子在不同临床病程的结节病诊断中很重要:血管紧张素转换酶活性水平与记忆DP Th17百分比之间存在直接相关性;疾病进展与消退显著降低了总CD45RA-记忆和CM Th17的绝对数量;肺外表现DP Th17、CD45RA-和EM DP Th17的比例显著增加;慢性结节病患者IL-17A、IFNγ、IL-12浓度显著升高,且IFNγ与血管紧张素转换酶活性呈正相关。
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Sarcoidosis clinical picture governs alterations in type 17 T helper cell subset composition and cytokine profile
Immune cell hyperactivation along with cytokines they overproduce plays an important role in sarcoidosis and related disease pathogenesis. A central place in the immunopathogenesis of sarcoidosis is held by diverse cell-mediated reactions governed by T helper (Th) cell populations including Th17 subsets and relevant signature cytokines. We studied peripheral blood plasma samples of the patients with sarcoidosis (n = 123): 18% with acute and 82% with chronic course. The control group — samples from healthy volunteers (n = 43). T cell subset composition was assessed by flow cytometry. Cytokine concentrations (pg/mL) were measured by multiplex analysis using xMAP technology (Luminex). The level of “classical” Th17 turned out to be significantly reduced in acute vs chronic sarcoidosis: 28.3% vs 33.3% (p = 0.046). The level of “double-positive” Th17 (DP Th17) was significantly increased in chronic and acute vs control group: 31.7% and 34.2% vs 26.2% (p < 0.001 in both cases), without differences patient inter-group; “non-classical” Th17.1 were shown to have significantly reduced level only in chronic vs healthy subjects: 27.9% and 35.9% (p < 0.001). Clinical and laboratory diagnostic characteristics for blood DP Th17 levels in CD45RA-negative Th effector memory cells in sarcoidosis: in acute sarcoidosis vs healthy subjects, they were characterized by sensitivity — 82%; specificity — 71%, whereas in chronic: 67% and 56%, respectively. In patients with sarcoidosis vs healthy subjects were found to have significantly increased level of IL-12 (p70) — 1.3 vs 0.56, p = 0.028; IL-17A — 1.5 vs 0.43, p < 0.001; IFNγ — 4.1 vs 1.1, p < 0.001; TNFα — 21.7 vs 6.7, p < 0.001. Thus, CCR6+ Th17 and DP Th17 subsets and relevant signature cytokines are important in diagnostics of sarcoidosis of varying clinical course: a direct correlation was shown between the level of angiotensin-converting enzyme activity and percentage of memory DP Th17; disease progression vs regression had significantly reduced absolute number of total CD45RA- memory and CM Th17; extrapulmonary manifestations had a significantly increased percentage of DP Th17 CD45RA- and EM DP Th17; in chronic sarcoidosis are significantly increased concentration of IL-17A, IFNγ, IL-12 and positively correlation between IFNγ and the activity of angiotensin-converting enzyme.
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来源期刊
Medical Immunology (Russia)
Medical Immunology (Russia) Medicine-Immunology and Allergy
CiteScore
0.70
自引率
0.00%
发文量
88
审稿时长
12 weeks
期刊介绍: The journal mission is to promote scientific achievements in fundamental and applied immunology to various medical fields, the publication of reviews, lectures, essays by leading domestic and foreign experts in the field of fundamental and experimental immunology, clinical immunology, allergology, immunodiagnostics and immunotherapy of infectious, allergy, autoimmune diseases and cancer.
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