Yilmaz Vuslat, Oflazer Piraye, Aysal Fikret, Parman Yeşim G, Direskeneli Haner, Deymeer Feza, Saruhan-Direskeneli Güher
Department of Physiology , and.
Autoimmunity. 2015 Jun;48(4):201-7. doi: 10.3109/08916934.2014.992517. Epub 2014 Dec 18.
B cells from myasthenia gravis (MG) patients with autoantibodies (Aab) against acetylcholine receptor (AChR), muscle-specific kinase (MuSK) or with no detectable Aab were investigated as cytokine producing cells in this study. B cells were evaluated for memory phenotypes and expressions of IL-10, IL-6 and IL-12A. Induced productions of IL-10, IL-6, IL-12p40, TNF-α and LT from isolated B cells in vitro were measured by immunoassays. MG patients receiving immunosuppressive treatment had higher proportions of memory B cells compared with healthy controls and untreated patients. With CD40 stimulation MG patients produced significantly lower levels of IL-10, IL-6. With CD40 and B cell receptor stimulation of B cells, TNF-α production also decreased in addition to these cytokines. The lower levels of these cytokine productions were not related to treatment. Our results confirm a disturbance of B cell subpopulations in MG subgroups on immunosuppressive treatment. B cell derived IL-10, IL-6 and TNF-α are down-regulated in MG, irrespective of different antibody productions. Ineffective cytokine production by B cells may be a susceptibility factor in dysregulation of autoimmune Aab production.
在本研究中,对患有抗乙酰胆碱受体(AChR)自身抗体(Aab)、肌肉特异性激酶(MuSK)自身抗体或无可检测Aab的重症肌无力(MG)患者的B细胞作为细胞因子产生细胞进行了研究。对B细胞的记忆表型以及白细胞介素-10(IL-10)、白细胞介素-6(IL-6)和白细胞介素-12A(IL-12A)的表达进行了评估。通过免疫测定法测量了体外分离的B细胞中IL-10、IL-6、白细胞介素-12p40(IL-12p40)、肿瘤坏死因子-α(TNF-α)和淋巴毒素(LT)的诱导产生量。与健康对照和未接受治疗的患者相比,接受免疫抑制治疗的MG患者记忆B细胞比例更高。经CD40刺激后,MG患者产生的IL-10、IL-6水平显著降低。在B细胞经CD40和B细胞受体刺激后,除了这些细胞因子外,TNF-α的产生也减少。这些细胞因子产生水平较低与治疗无关。我们的结果证实了免疫抑制治疗的MG亚组中B细胞亚群存在紊乱。无论抗体产生情况如何,MG患者中B细胞衍生的IL-10、IL-6和TNF-α均下调。B细胞产生细胞因子无效可能是自身免疫性Aab产生失调的一个易感因素。