TY - JOUR
T1 - Generation of plasma cells and CD27−IgD− B cells during hantavirus infection is associated with distinct pathological findings
AU - Kerkman, Priscilla F.
AU - Dernstedt, Andy
AU - Tadala, Lalitha
AU - Mittler, Eva
AU - Dannborg, Mirjam
AU - Sundling, Christopher
AU - Maleki, Kimia T.
AU - Tauriainen, Johanna
AU - Tuiskunen-Bäck, Anne
AU - Wigren Byström, Julia
AU - Ocaya, Pauline
AU - Thunberg, Therese
AU - Jangra, Rohit K.
AU - Román-Sosa, Gleyder
AU - Guardado-Calvo, Pablo
AU - Rey, Felix A.
AU - Klingström, Jonas
AU - Chandran, Kartik
AU - Puhar, Andrea
AU - Ahlm, Clas
AU - Forsell, Mattias N.E.
N1 - Publisher Copyright:
© 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - B cells
KW - antibodies
KW - atypical B cells
KW - haemorrhagic fever with renal syndrome
KW - hantavirus
KW - plasmablasts
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U2 - 10.1002/cti2.1313
DO - 10.1002/cti2.1313
M3 - Article
AN - SCOPUS:85111325845
SN - 2050-0068
VL - 10
JO - Clinical and Translational Immunology
JF - Clinical and Translational Immunology
IS - 7
M1 - e1313
ER -