白细胞介素-17A主动免疫对 pristane 诱导的狼疮模型中 B 细胞功能及感染风险的影响。

Effect of active immunization with IL-17A on B cell function and infection risk in pristane-induced lupus model.

作者信息

Handono Kusworini, Pratama Mirza Zaka, Sari Dita Kartika, Hermawan Hanestya Oky, Agdana Hafishtyawan Maulidyananta, Kawuningan Keryasta Becik, Nur'aini Nafisah, Hasanah Dian, Kalim Handono

机构信息

Department of Clinical Pathology, Universitas Brawijaya, Malang, Indonesia.

Rheumatology and Immunology Division, Department of Internal Medicine, Universitas Brawijaya, Malang, Indonesia.

出版信息

Int J Rheum Dis. 2018 Jun;21(6):1277-1286. doi: 10.1111/1756-185X.13325.

DOI:10.1111/1756-185X.13325

PMID:29879320

Abstract

PURPOSE

The aim of this study was to determine the effect of active immunization of interleukin (IL)-17A to inhibit B cell functions and monitor the risk of infection in a pristane-induced lupus mice model.

METHODS

Female Balb/c mice were given a single intraperitoneal injection of 0.5 mL pristane. IL-17A was coupled to keyhole limpet hemocyanin (KLH) and given to mice in three different doses: D0 (0 μg/mL), D1 (1 μg/mL), and D2 (10 μg/mL). The vaccine was given three times with 3-week intervals. At day 42, mice were injected intraperitoneally with methicillin-resistant Staphylococcus aureus (MRSA) and monitored for 3 weeks. Plasma cells proliferation, Th17 and plasma cell percentages were measured by flow cytometry; anti-IL-17A antibody titers, IL-17A, and anti-double-stranded DNA (anti-dsDNA) levels were measured by enzyme-linked immunosorbent assay; and MRSA colonization was measured by bacterial counter.

RESULTS

Anti-IL-17A antibody titers were significantly higher in D2 compared to D0 (P = 0.012). Serum IL-17A levels were also significantly lower in D2 compared to D0 (P = 0.000) while Th17 percentages were not significantly different between groups. D2 was also had significantly lower anti-dsDNA (P = 0.021), lower plasma cell percentages (P = 0.000) and lower B cell proliferation rate (P = 0.001) compared to D0. Analysis for the risk of infection also revealed that D2 did not increase the risk of infection compared to D0 (P = 0.504).

CONCLUSION

Active immunization with IL-17A coupled to KLH was able to induce a high titer of neutralizing antibodies against IL-17A and inhibit B cell functions without increasing the risk of infection in a pristane-induced lupus mice model.

摘要

目的

本研究旨在确定白细胞介素（IL）-17A主动免疫对抑制B细胞功能的影响，并监测在 pristane 诱导的狼疮小鼠模型中的感染风险。

方法

雌性 Balb/c 小鼠腹腔内单次注射 0.5 mL pristane。将 IL-17A 与钥孔戚血蓝蛋白（KLH）偶联，并以三种不同剂量给予小鼠：D0（0 μg/mL）、D1（1 μg/mL）和 D2（10 μg/mL）。疫苗每隔 3 周注射三次。在第 42 天，小鼠腹腔内注射耐甲氧西林金黄色葡萄球菌（MRSA），并监测 3 周。通过流式细胞术测量浆细胞增殖、Th17 和浆细胞百分比；通过酶联免疫吸附测定法测量抗 IL-17A 抗体滴度、IL-17A 和抗双链 DNA（抗 dsDNA）水平；通过细菌计数器测量 MRSA 定植。

结果

与 D0 相比，D2 中的抗 IL-17A 抗体滴度显著更高（P = 0.012）。与 D0 相比，D2 中的血清 IL-17A 水平也显著更低（P = 0.000），而各组之间的 Th17 百分比没有显著差异。与 D0 相比，D2 的抗 dsDNA 也显著更低（P = 0.021）、浆细胞百分比更低（P = 0.000）和 B 细胞增殖率更低（P = 0.001）。对感染风险的分析还显示，与 D0 相比，D2 没有增加感染风险（P = 0.504）。