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

Authors:
Open Access
Publisher website
Google Scholar
Abstract
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.
Funding Information
  • Luonnontieteiden ja Tekniikan Tutkimuksen Toimikunta (308613)
  • Luonnontieteiden ja Tekniikan Tutkimuksen Toimikunta (308613)
  • Terveyden Tutkimuksen Toimikunta (321809)
  • Terveyden Tutkimuksen Toimikunta (321809)
  • Competitive State Research Financing (Financing of the Expert Responsibility Area of Tampere University Hospital)
  • Sigrid Juséliuksen Säätiö
  • Sigrid Juséliuksen Säätiö
  • Magnus Ehrnroothin Säätiö
  • Foundation for Clinical Chemistry Research
  • Laboratoriolääketieteen edistämissäätiö
  • Suomalais-Norjalainen Lääketieteen Säätiö

This publication has 43 references indexed in Scilit: