探讨抗中性粒细胞胞质抗体相关性血管炎中髓过氧化物酶和蛋白酶 3 相关的循环特异性 Th17 细胞的频率。
Exploring Frequencies of Circulating Specific Th17 Cells against Myeloperoxidase and Proteinase 3 in ANCA Associated Vasculitis.
机构信息
Hospital Universitari de Bellvitge, Nephrology Unit. Hospitalet de Llobregat, 08907 Barcelona, Spain.
IDIBELL Institut d'Investigacions Biomèdiques, Hospitalet de Llobregat, 08907 Barcelona, Spain.
出版信息
Int J Mol Sci. 2019 Nov 20;20(23):5820. doi: 10.3390/ijms20235820.
UNLABELLED
Background: The role of the T helper 17 (Th17) cell subset in anti-neutrophil cytoplasm antibodies (ANCA) associated vasculitis (AAV) is controversial. We hypothesized that a specific Th17 response to myeloperoxidase (MPO) or proteinase 3 (PR3) is detectable in AAV patients and is different among the disease phases.
METHODS
We analyzed 43 AAV patients with renal involvement (21 acute and 22 remission patients), and 12 healthy controls. Peripheral blood mononuclear cells (PBMCs) were cultured with PR3/MPO over 48 h. Thereafter, frequencies of MPO/PR3-specific Th17 cells were assessed using an enzyme-linked immunosorbent spot (ELISpot) assay. Supernatant IL-17 concentration was quantified using ELISA. Finally, specific Th17 response after depletion of T regulatory lymphocytes (T-regs) in some remission patients was compared to the non T-reg-depleted response.
RESULTS
Specific Th17 cell number was higher in acute patients compared to remission ( = 0.004). Specific Th17 cell number performed well in the disease activity detection (ROC curve area under the curve (AUC) = 0.87; = 0.0001) with an optimal cut-off of 6 spots/million. Patients above this cut-off showed higher serum creatinine ( = 0.004), C-reactive protein (CRP) ( = 0.001) and ANCA titer ( = 0.032). Supernatant IL-17 concentration was higher in acute patients compared to remission ( = 0.035) and did not normalize to healthy control levels ( = 0.01).
CONCLUSIONS
A specific Th17 cell response is present in AAV patients. This response is more pronounced in the acute phase, but persists in remission.
背景
辅助性 T 细胞 17（Th17）亚群在抗中性粒细胞胞质抗体（ANCA）相关性血管炎（AAV）中的作用存在争议。我们假设在 AAV 患者中可检测到针对髓过氧化物酶（MPO）或蛋白酶 3（PR3）的特定 Th17 反应，且在疾病的不同阶段存在差异。
方法
我们分析了 43 例有肾脏受累的 AAV 患者（21 例急性期和 22 例缓解期患者）和 12 名健康对照者。将外周血单核细胞（PBMC）与 PR3/MPO 共培养 48 小时。此后，通过酶联免疫斑点（ELISpot）测定法评估 MPO/PR3 特异性 Th17 细胞的频率。使用 ELISA 定量上清液中白细胞介素-17（IL-17）的浓度。最后，在一些缓解期患者中，比较 T 调节性淋巴细胞（T-reg）耗竭前后的特定 Th17 反应。
结果
与缓解期相比，急性期患者的特定 Th17 细胞数更高（ = 0.004）。特定 Th17 细胞数在疾病活动检测中表现良好（ROC 曲线下面积（AUC）= 0.87； = 0.0001），最佳截断值为 6 个斑点/百万。高于该截断值的患者血清肌酐（ = 0.004）、C 反应蛋白（CRP）（ = 0.001）和 ANCA 滴度（ = 0.032）更高。与缓解期相比，急性期患者的上清液 IL-17 浓度更高（ = 0.035），但未恢复至健康对照组水平（ = 0.01）。
结论
AAV 患者存在针对 Th17 细胞的特定反应。该反应在急性期更为明显，但在缓解期仍持续存在。
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