Clinical & translational immunology · 2021
Generation of plasma cells and CD27-IgD- B cells during hantavirus infection is associated with distinct pathological findings.
СтатьяНазвание и аннотация: Перевод в очереди
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Kerkman Priscilla F, Dernstedt Andy, Tadala Lalitha, Mittler Eva, Dannborg Mirjam, Sundling Christopher, Maleki Kimia T, Tauriainen Johanna, Tuiskunen-Bäck Anne, Wigren Byström Julia, Ocaya Pauline, Thunberg Therese, Jangra Rohit K, Román-Sosa Gleyder, Guardado-Calvo Pablo, Rey Felix A, Klingström Jonas, Chandran Kartik, Puhar Andrea, Ahlm Clas, Forsell Mattias Ne
Аннотация
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSION: 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.