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Generation of Plasma Cells and CD27IgD B Cells During Hantavirus Infection is Associated with Distinct Pathological Findings

Abstract

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 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 CD27IgD B cells and CD27 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.

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References
1.
Centuori S, Gomes C, Kim S, Putnam C, Larsen B, Garland L . Double-negative (CD27IgD) B cells are expanded in NSCLC and inversely correlate with affinity-matured B cell populations. J Transl Med. 2018; 16(1):30. PMC: 5815250. DOI: 10.1186/s12967-018-1404-z. View

2.
Joosten S, van Meijgaarden K, Del Nonno F, Baiocchini A, Petrone L, Vanini V . Patients with Tuberculosis Have a Dysfunctional Circulating B-Cell Compartment, Which Normalizes following Successful Treatment. PLoS Pathog. 2016; 12(6):e1005687. PMC: 4909319. DOI: 10.1371/journal.ppat.1005687. View

3.
Garcia M, Iglesias A, Landoni V, Bellomo C, Bruno A, Cordoba M . Massive plasmablast response elicited in the acute phase of hantavirus pulmonary syndrome. Immunology. 2017; 151(1):122-135. PMC: 5382343. DOI: 10.1111/imm.12713. View

4.
MacNeil A, Comer J, Ksiazek T, Rollin P . Sin Nombre virus-specific immunoglobulin M and G kinetics in hantavirus pulmonary syndrome and the role played by serologic responses in predicting disease outcome. J Infect Dis. 2010; 202(2):242-6. DOI: 10.1086/653482. View

5.
Sullivan R, Ssewanyana I, Wamala S, Nankya F, Jagannathan P, Tappero J . B cell sub-types following acute malaria and associations with clinical immunity. Malar J. 2016; 15:139. PMC: 4778296. DOI: 10.1186/s12936-016-1190-0. View