Gupta Nikhil, Kabeerdoss Jayakanthan, Mohan Hindhumathi, Goel Ruchika, Danda Debashish
Department of Clinical Immunology and Rheumatology, Christian Medical College, Vellore, Tamil Nadu, India.
Open Rheumatol J. 2018 Mar 28;12:30-36. doi: 10.2174/1874312901812010030. eCollection 2018.
Suspicion on the association between Takayasu Arteritis (TA) and Tubcerculosis (TB) has been in vogue for years. Prevalence of TB in TA is reported to be higher. We aimed to study innate immune responses in patients with TA on exposure to Trehalose-6,6-dibehenate (TDB), a synthetic analogue of Trehalose-6,6-Dimycolate (TDM, also known as mycobacterial cord factor) in comparison with healthy controls.
Patients with type V TA, satisfying 1990 ACR criteria, and age and sex matched healthy controls were recruited. PBMCs were cultured with 5µg/ml, 50µg/ml or without any TDB for 48 hours in RPMI medium inside a 5% Co2 incubator. IL-6, TNF-α and IL-17 were measured in cell culture supernatant, which was separated from the cells at the end of the incubation period. Gene expressions of IL-6, IL-8, TNFα, IFN-γ, MINCLE and BCL-10 were quantified in real time PCR using specific primers and SYBR green chemistry.
Twenty two TA patients and 21 healthy controls were recruited. Both patients and controls showed response by secreting IL-6 and TNF-α upon stimulation by TDB. Relative induction (TDB stimulated TA sample / unstimulated control) of IL-6 was significantly higher in TA [31.88(0.74-168)] patients as compared to healthy controls [1.931(0.644-8.21); p<0.002], when co-cultured with 50µg/ml TDB. The expression of MINCLE, the TDB receptor was higher in TA samples than healthy controls upon TDB stimulation.
Stimulation with mycobacterial synthetic analogue led to higher secretion of IL-6 and higher expression of MINCLE in PBMCs of patients with TA as compared to healthy controls.
多年来，人们一直怀疑高安动脉炎（TA）与结核病（TB）之间存在关联。据报道，TA患者中TB的患病率较高。我们旨在研究与健康对照相比，TA患者在接触海藻糖-6,6-二山嵛酸酯（TDB，海藻糖-6,6-二霉菌酸酯（TDM，也称为分枝杆菌索状因子）的合成类似物）时的固有免疫反应。
招募符合1990年美国风湿病学会（ACR）标准的V型TA患者以及年龄和性别匹配的健康对照。将外周血单核细胞（PBMC）在含有5μg/ml、50μg/ml TDB或不含任何TDB的RPMI培养基中，于5%二氧化碳培养箱中培养48小时。在培养期结束时从细胞中分离出细胞培养上清液，检测其中白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）和白细胞介素-17（IL-17）的水平。使用特异性引物和SYBR Green化学方法通过实时聚合酶链反应（PCR）对IL-6、IL-8、TNFα、干扰素-γ（IFN-γ）、巨噬细胞诱导型C型凝集素（MINCLE）和B细胞淋巴瘤/白血病-10（BCL-10）的基因表达进行定量分析。
招募了22例TA患者和21例健康对照。患者和对照在受到TDB刺激后均通过分泌IL-6和TNF-α做出反应。当与50μg/ml TDB共同培养时，TA患者[31.88(0.74 - 168)]中IL-6的相对诱导值（TDB刺激的TA样本/未刺激的对照）显著高于健康对照[1.931(0.644 - 8.21)；p<0.002]。在TDB刺激下，TA样本中TDB受体MINCLE的表达高于健康对照。
与健康对照相比，用分枝杆菌合成类似物刺激导致TA患者PBMC中IL-6分泌增加以及MINCLE表达升高。
