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PtpA and PknG Proteins Secreted by Mycobacterium avium subsp. paratuberculosis are Recognized by Sera from Patients with Rheumatoid Arthritis: A Case-Control Study.
Journal of Inflammation Research ( IF 4.5 ) Pub Date : 2019-12-03 , DOI: 10.2147/jir.s220960 Marco Bo 1 , Gian Luca Erre 2 , Horacio Bach 3 , Yael N Slavin 3 , Piera Angela Manchia 4 , Giuseppe Passiu 2 , Leonardo A Sechi 1
Journal of Inflammation Research ( IF 4.5 ) Pub Date : 2019-12-03 , DOI: 10.2147/jir.s220960 Marco Bo 1 , Gian Luca Erre 2 , Horacio Bach 3 , Yael N Slavin 3 , Piera Angela Manchia 4 , Giuseppe Passiu 2 , Leonardo A Sechi 1
Affiliation
Purpose: Rheumatoid arthritis (RA) can result from complex interactions between the affected person’s genetic background and environment. Viral and bacterial infections may play a pathogenetic role in RA through different mechanisms of action. We aimed to evaluate the presence of antibodies (Abs) directed against two proteins of Mycobacterium avium subsp. paratuberculosis (MAP) in sera of RA subjects, which are crucial for the survival of the pathogen within macrophages. Moreover, we analyzed the correlation of immune response to both proteins with the following homologous peptides: BOLF1305–320, MAP_402718–32 and IRF5424–434 to understand how the synergic role of Epstein–Barr virus (EBV) and MAP infection in genetically predisposed subjects may lead to a possible deregulation of interferon regulatory factor 5 (IRF5).
Materials and methods: The presence of Abs against protein tyrosine phosphatase A (PtpA) and protein kinase G (PknG) in sera from Sardinian RA patients (n=84) and healthy volunteers (HCs, n=79) was tested by indirect ELISA.
Results: RA sera showed a remarkably high frequency of reactivity against PtpA in comparison to HCs (48.8% vs 7.6%; p<0.001) and lower but statistically significant responses towards PknG (27.4% vs 10.1%; p=0.0054). We found a significant linear correlation between the number of swollen joints and the concentrations of antibodies against PtpA (p=0.018). Furthermore, a significant bivariate correlation between PtpA and MAP MAP_402718–32 peptide has been found, suggesting that MAP infection may induce a secondary immune response through cross-reaction with IRF5 (R2=0.5).
Conclusion: PtpA and PknG are strongly recognized in RA which supports the hypothesis that MAP infection may be involved in the pathogenesis of RA.
Keywords: Mycobacterium avium subsp. paratuberculosis, PtpA, PknG, virulence factors, rheumatoid arthritis, immune response
中文翻译：
鸟分枝杆菌亚种分泌的 PtpA 和 PknG 蛋白。类风湿关节炎患者的血清可识别副结核病：病例对照研究。
目的：类风湿性关节炎 (RA) 可能是受累者的遗传背景和环境之间复杂的相互作用造成的。病毒和细菌感染可能通过不同的作用机制在 RA 中发挥致病作用。我们旨在评估针对鸟分枝杆菌亚种的两种蛋白质的抗体 (Abs) 的存在。RA 受试者血清中的副结核病(MAP) 对巨噬细胞内病原体的存活至关重要。此外，我们分析了对两种蛋白质的免疫反应与以下同源肽的相关性：BOLF1 305-320、MAP_4027 18-32和 IRF5 424-434了解 Epstein-Barr 病毒 (EBV) 和 MAP 感染在遗传易感受试者中的协同作用如何可能导致干扰素调节因子 5 (IRF5) 的失调。
材料和方法：通过间接 ELISA 检测撒丁岛 RA 患者 (n=84) 和健康志愿者 (HCs, n=79) 血清中是否存在针对蛋白酪氨酸磷酸酶 A (PtpA) 和蛋白激酶 G (PknG) 的抗体。
结果：与 HC 相比，RA 血清对 PtpA 的反应频率非常高（48.8% 对 7.6%；p <0.001），对 PknG 的反应较低但具有统计学意义（27.4% 对 10.1%；p=0.0054）。我们发现肿胀关节的数量与针对 PtpA 的抗体浓度之间存在显着的线性相关性（p = 0.018）。此外，已发现 PtpA 和 MAP MAP_4027 18-32肽之间存在显着的双变量相关性，表明 MAP 感染可能通过与 IRF5 的交叉反应诱导二次免疫反应（R 2 =0.5）。
结论： PtpA和PknG在RA中得到高度认可，支持MAP感染可能参与RA发病机制的假设。
关键词： 鸟分枝杆菌亚种。副结核病, PtpA, PknG, 毒力因子, 类风湿性关节炎, 免疫反应
更新日期：2019-12-03
Materials and methods: The presence of Abs against protein tyrosine phosphatase A (PtpA) and protein kinase G (PknG) in sera from Sardinian RA patients (n=84) and healthy volunteers (HCs, n=79) was tested by indirect ELISA.
Results: RA sera showed a remarkably high frequency of reactivity against PtpA in comparison to HCs (48.8% vs 7.6%; p<0.001) and lower but statistically significant responses towards PknG (27.4% vs 10.1%; p=0.0054). We found a significant linear correlation between the number of swollen joints and the concentrations of antibodies against PtpA (p=0.018). Furthermore, a significant bivariate correlation between PtpA and MAP MAP_402718–32 peptide has been found, suggesting that MAP infection may induce a secondary immune response through cross-reaction with IRF5 (R2=0.5).
Conclusion: PtpA and PknG are strongly recognized in RA which supports the hypothesis that MAP infection may be involved in the pathogenesis of RA.
Keywords: Mycobacterium avium subsp. paratuberculosis, PtpA, PknG, virulence factors, rheumatoid arthritis, immune response
中文翻译：
鸟分枝杆菌亚种分泌的 PtpA 和 PknG 蛋白。类风湿关节炎患者的血清可识别副结核病：病例对照研究。
目的：类风湿性关节炎 (RA) 可能是受累者的遗传背景和环境之间复杂的相互作用造成的。病毒和细菌感染可能通过不同的作用机制在 RA 中发挥致病作用。我们旨在评估针对鸟分枝杆菌亚种的两种蛋白质的抗体 (Abs) 的存在。RA 受试者血清中的副结核病(MAP) 对巨噬细胞内病原体的存活至关重要。此外，我们分析了对两种蛋白质的免疫反应与以下同源肽的相关性：BOLF1 305-320、MAP_4027 18-32和 IRF5 424-434了解 Epstein-Barr 病毒 (EBV) 和 MAP 感染在遗传易感受试者中的协同作用如何可能导致干扰素调节因子 5 (IRF5) 的失调。
材料和方法：通过间接 ELISA 检测撒丁岛 RA 患者 (n=84) 和健康志愿者 (HCs, n=79) 血清中是否存在针对蛋白酪氨酸磷酸酶 A (PtpA) 和蛋白激酶 G (PknG) 的抗体。
结果：与 HC 相比，RA 血清对 PtpA 的反应频率非常高（48.8% 对 7.6%；p <0.001），对 PknG 的反应较低但具有统计学意义（27.4% 对 10.1%；p=0.0054）。我们发现肿胀关节的数量与针对 PtpA 的抗体浓度之间存在显着的线性相关性（p = 0.018）。此外，已发现 PtpA 和 MAP MAP_4027 18-32肽之间存在显着的双变量相关性，表明 MAP 感染可能通过与 IRF5 的交叉反应诱导二次免疫反应（R 2 =0.5）。
结论： PtpA和PknG在RA中得到高度认可，支持MAP感染可能参与RA发病机制的假设。
关键词： 鸟分枝杆菌亚种。副结核病, PtpA, PknG, 毒力因子, 类风湿性关节炎, 免疫反应
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