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:	Jussi Hepojoki, Luz E Cabrera, Satu Hepojoki, Carla Bellomo, Lauri Kareinen, Leif C Andersson, Antti Vaheri, Satu Mäkelä, Jukka Mustonen, Olli Vapalahti, Valeria Martinez, Tomas Strandin
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0a968ea75f3146368771f8d10ee984ce
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spelling	oai:doaj.org-article:0a968ea75f3146368771f8d10ee984ce2021-12-02T20:00:17ZHantavirus infection-induced B cell activation elevates free light chains levels in circulation.1553-73661553-737410.1371/journal.ppat.1009843https://doaj.org/article/0a968ea75f3146368771f8d10ee984ce2021-08-01T00:00:00Zhttps://doi.org/10.1371/journal.ppat.1009843https://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374In 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.Jussi HepojokiLuz E CabreraSatu HepojokiCarla BellomoLauri KareinenLeif C AnderssonAntti VaheriSatu MäkeläJukka MustonenOlli VapalahtiValeria MartinezTomas StrandinPublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 17, Iss 8, p e1009843 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Jussi Hepojoki Luz E Cabrera Satu Hepojoki Carla Bellomo Lauri Kareinen Leif C Andersson Antti Vaheri Satu Mäkelä Jukka Mustonen Olli Vapalahti Valeria Martinez Tomas Strandin Hantavirus infection-induced B cell activation elevates free light chains levels in circulation.
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.
format	article
author	Jussi Hepojoki Luz E Cabrera Satu Hepojoki Carla Bellomo Lauri Kareinen Leif C Andersson Antti Vaheri Satu Mäkelä Jukka Mustonen Olli Vapalahti Valeria Martinez Tomas Strandin
author_facet	Jussi Hepojoki Luz E Cabrera Satu Hepojoki Carla Bellomo Lauri Kareinen Leif C Andersson Antti Vaheri Satu Mäkelä Jukka Mustonen Olli Vapalahti Valeria Martinez Tomas Strandin
author_sort	Jussi Hepojoki
title	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_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_sort	hantavirus infection-induced b cell activation elevates free light chains levels in circulation.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/0a968ea75f3146368771f8d10ee984ce
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Hantavirus infection-induced B cell activation elevates free light chains levels in circulation.

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