Generation of plasma cells and CD27(-)IgD(-) B cells during hantavirus infection is associated with distinct pathological findings.
Generation of plasma cells and CD27(-)IgD(-) B cells during hantavirus infection is associated with distinct pathological findings.
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DOI：
10.1002/cti2.1313
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发表时间：
2021
影响因子：
5.8
通讯作者：
Forsell MN
中科院分区：
文献类型：
--
作者：
Kerkman PF;Dernstedt A;Tadala L;Mittler E;Dannborg M;Sundling C;Maleki KT;Tauriainen J;Tuiskunen-Bäck A;Wigren Byström J;Ocaya P;Thunberg T;Jangra RK;Román-Sosa G;Guardado-Calvo P;Rey FA;Klingström J;Chandran K;Puhar A;Ahlm C;Forsell MN
人类汉坦病毒感染可引起肾综合征出血热（HFRS）。致病机制尚不完全清楚，也不清楚它们是否影响体液免疫系统。本研究的目的是调查汉坦病毒感染的体液免疫反应，并将其与HFRS的典型特征：血小板减少和一过性肾功能障碍联系起来。我们对26例汉坦病毒患者的纵向抗病毒B细胞反应进行了全面的表征，并将其与配对的临床数据相结合。此外，我们测量了循环中的细胞外三磷酸腺苷（ATP）及其分解产物，并进行了体外刺激以解决其对B细胞的影响。我们发现血小板减少症与循环中浆母细胞频率升高有关。相反，肾功能障碍表明CD27−IgD−B细胞和CD27−/低质母细胞的积累。最后，我们提供的证据表明，在汉坦病毒感染期间，高水平的细胞外ATP和基质金属蛋白酶8可以促进CD27的脱落。我们的研究结果表明，血小板减少症和肾功能障碍对体液免疫系统有明显不同的影响。此外，汉坦病毒感染个体循环中细胞外ATP水平显著升高。我们进行了一项综合研究，将两种与肾综合征出血热（HFRS）、血小板减少症和肾功能障碍相关的病理与循环B细胞区室（细胞和抗体）的变化联系起来。我们发现血小板减少症与循环中激活的和静止的浆母细胞和浆细胞的动员有关。然而，肾功能障碍水平与患者中和抗体的纵向发展有关，并与循环中浆母细胞和B细胞表面CD27表达的减少有关。CD27的低表达可能是由于ATP水平升高，ATP可能通过MMP - 8依赖性机制导致B细胞中CD27的脱落。
Human hantavirus infections can cause haemorrhagic fever with renal syndrome (HFRS). The pathogenic mechanisms are not fully understood, nor if they affect the humoral immune system. The objective of this study was to investigate humoral immune responses to hantavirus infection and to correlate them to the typical features of HFRS: thrombocytopenia and transient kidney dysfunction. We performed a comprehensive characterisation of longitudinal antiviral B‐cell responses of 26 hantavirus patients and combined this with paired clinical data. In addition, we measured extracellular adenosine triphosphate (ATP) and its breakdown products in circulation and performed in vitro stimulations to address its effect on B cells. We found that thrombocytopenia was correlated to an elevated frequency of plasmablasts in circulation. In contrast, kidney dysfunction was indicative of an accumulation of CD27−IgD− B cells and CD27−/low plasmablasts. Finally, we provide evidence that high levels of extracellular ATP and matrix metalloproteinase 8 can contribute to shedding of CD27 during human hantavirus infection. Our findings demonstrate that thrombocytopenia and kidney dysfunction associate with distinctly different effects on the humoral immune system. Moreover, hantavirus‐infected individuals have significantly elevated levels of extracellular ATP in circulation. We show a comprehensive study to correlate two pathologies associated with haemorrhagic fever with renal syndrome (HFRS), thrombocytopenia and kidney dysfunction, with changes in the circulating B‐cell compartment (cells and antibodies). We show that thrombocytopenia is associated with mobilization of both activated and resting plasmablasts and plasma cells in circulation. However, the level of kidney dysfunction associated with longitudinal development of neutralizing antibodies in patients and associated with the reduction of surface CD27 expression on both plasmablasts and B cells in circulation. The low CD27 expression might be explained by elevated levels of ATP that could contribute to shedding of CD27 from B cells by a MMP‐8‐dependent mechanism.
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影响因子：
5.2
作者：
Hepojoki J;Vaheri A;Strandin T
通讯作者：
Strandin T
影响因子：
5.4
作者：
Lindgren, Therese;Ahlm, Clas;Bjorkstrom, Niklas K.
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Bjorkstrom, Niklas K.
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Evander, Magnus;Eriksson, Irene;Allard, Annika
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Allard, Annika
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6.4
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Connolly-Andersen, Anne-Marie;Sundberg, Erik;Nilsson, Sofie
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Nilsson, Sofie
影响因子：
6.1
作者：
Ala-Houhala, I;Koskinen, M;Pasternack, A
通讯作者：
Pasternack, A