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Hantavirus infection-induced B cell activation elevates free light chains levels in circulation

In humans, orthohantaviruses can cause hemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). An earlier study reported that acute Andes virus HPS caused a massive and transient elevation in the number of circulating plasmablasts with specificity towards both viral and...

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Autores principales: Hepojoki, Jussi, Cabrera, Luz E., Hepojoki, Satu, Bellomo, Carla, Kareinen, Lauri, Andersson, Leif C., Vaheri, Antti, Mäkelä, Satu, Mustonen, Jukka, Vapalahti, Olli, Martinez, Valeria, Strandin, Tomas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382192/
https://www.ncbi.nlm.nih.gov/pubmed/34379707
http://dx.doi.org/10.1371/journal.ppat.1009843
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author Hepojoki, Jussi
Cabrera, Luz E.
Hepojoki, Satu
Bellomo, Carla
Kareinen, Lauri
Andersson, Leif C.
Vaheri, Antti
Mäkelä, Satu
Mustonen, Jukka
Vapalahti, Olli
Martinez, Valeria
Strandin, Tomas
author_facet Hepojoki, Jussi
Cabrera, Luz E.
Hepojoki, Satu
Bellomo, Carla
Kareinen, Lauri
Andersson, Leif C.
Vaheri, Antti
Mäkelä, Satu
Mustonen, Jukka
Vapalahti, Olli
Martinez, Valeria
Strandin, Tomas
author_sort Hepojoki, Jussi
collection PubMed
description In humans, orthohantaviruses can cause hemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). An earlier study reported that acute Andes virus HPS caused a massive and transient elevation in the number of circulating plasmablasts with specificity towards both viral and host antigens suggestive of polyclonal B cell activation. Immunoglobulins (Igs), produced by different B cell populations, comprise heavy and light chains; however, a certain amount of free light chains (FLCs) is constantly present in serum. Upregulation of FLCs, especially clonal species, associates with renal pathogenesis by fibril or deposit formations affecting the glomeruli, induction of epithelial cell disorders, or cast formation in the tubular network. We report that acute orthohantavirus infection increases the level of Ig FLCs in serum of both HFRS and HPS patients, and that the increase correlates with the severity of acute kidney injury in HFRS. The fact that the kappa to lambda FLC ratio in the sera of HFRS and HPS patients remained within the normal range suggests polyclonal B cell activation rather than proliferation of a single B cell clone. HFRS patients demonstrated increased urinary excretion of FLCs, and we found plasma cell infiltration in archival patient kidney biopsies that we speculate to contribute to the observed FLC excreta. Analysis of hospitalized HFRS patients’ peripheral blood mononuclear cells showed elevated plasmablast levels, a fraction of which stained positive for Puumala virus antigen. Furthermore, B cells isolated from healthy donors were susceptible to Puumala virus in vitro, and the virus infection induced increased production of Igs and FLCs. The findings propose that hantaviruses directly activate B cells, and that the ensuing intense production of polyclonal Igs and FLCs may contribute to acute hantavirus infection-associated pathological findings.
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spelling pubmed-83821922021-08-24 Hantavirus infection-induced B cell activation elevates free light chains levels in circulation Hepojoki, Jussi Cabrera, Luz E. Hepojoki, Satu Bellomo, Carla Kareinen, Lauri Andersson, Leif C. Vaheri, Antti Mäkelä, Satu Mustonen, Jukka Vapalahti, Olli Martinez, Valeria Strandin, Tomas PLoS Pathog Research Article In humans, orthohantaviruses can cause hemorrhagic fever with renal syndrome (HFRS) or hantavirus pulmonary syndrome (HPS). An earlier study reported that acute Andes virus HPS caused a massive and transient elevation in the number of circulating plasmablasts with specificity towards both viral and host antigens suggestive of polyclonal B cell activation. Immunoglobulins (Igs), produced by different B cell populations, comprise heavy and light chains; however, a certain amount of free light chains (FLCs) is constantly present in serum. Upregulation of FLCs, especially clonal species, associates with renal pathogenesis by fibril or deposit formations affecting the glomeruli, induction of epithelial cell disorders, or cast formation in the tubular network. We report that acute orthohantavirus infection increases the level of Ig FLCs in serum of both HFRS and HPS patients, and that the increase correlates with the severity of acute kidney injury in HFRS. The fact that the kappa to lambda FLC ratio in the sera of HFRS and HPS patients remained within the normal range suggests polyclonal B cell activation rather than proliferation of a single B cell clone. HFRS patients demonstrated increased urinary excretion of FLCs, and we found plasma cell infiltration in archival patient kidney biopsies that we speculate to contribute to the observed FLC excreta. Analysis of hospitalized HFRS patients’ peripheral blood mononuclear cells showed elevated plasmablast levels, a fraction of which stained positive for Puumala virus antigen. Furthermore, B cells isolated from healthy donors were susceptible to Puumala virus in vitro, and the virus infection induced increased production of Igs and FLCs. The findings propose that hantaviruses directly activate B cells, and that the ensuing intense production of polyclonal Igs and FLCs may contribute to acute hantavirus infection-associated pathological findings. Public Library of Science 2021-08-11 /pmc/articles/PMC8382192/ /pubmed/34379707 http://dx.doi.org/10.1371/journal.ppat.1009843 Text en © 2021 Hepojoki et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Hepojoki, Jussi
Cabrera, Luz E.
Hepojoki, Satu
Bellomo, Carla
Kareinen, Lauri
Andersson, Leif C.
Vaheri, Antti
Mäkelä, Satu
Mustonen, Jukka
Vapalahti, Olli
Martinez, Valeria
Strandin, Tomas
Hantavirus infection-induced B cell activation elevates free light chains levels in circulation
title Hantavirus infection-induced B cell activation elevates free light chains levels in circulation
title_full Hantavirus infection-induced B cell activation elevates free light chains levels in circulation
title_fullStr Hantavirus infection-induced B cell activation elevates free light chains levels in circulation
title_full_unstemmed Hantavirus infection-induced B cell activation elevates free light chains levels in circulation
title_short Hantavirus infection-induced B cell activation elevates free light chains levels in circulation
title_sort hantavirus infection-induced b cell activation elevates free light chains levels in circulation
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8382192/
https://www.ncbi.nlm.nih.gov/pubmed/34379707
http://dx.doi.org/10.1371/journal.ppat.1009843
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