Thrombocytopenia associates with the severity of inflammation and variables reflecting capillary leakage in Puumala Hantavirus infection, an analysis of 546 Finnish patients

Outinen, Tuula; Laine, Outi; Mäkelä, Satu; Pörsti, Ilkka; Huhtala, Heini; Vaheri, Antti; Mustonen, Jukka

doi:10.1080/23744235.2016.1192719

Cited by 30 publications

(38 citation statements)

References 39 publications

(80 reference statements)

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“…We further demonstrated that the thrombocytopenia in patients inversely correlated with viral load (r=−0.73; p<0.0001), but there was no significant correlation with the elevated levels of CRP and creatinine (Figure 1F). The lack of a correlation between thrombocytopenia and serum creatinine was in accordance with findings in a previous study of over 500 HFRS patients in Finland (22). Collectively, these data confirmed a potential of longitudinal studies of HFRS to reveal whether thrombocytopenia or kidney dysfunction may differentially affect the humoral immune response to hantavirus infection.…”

Section: Resultssupporting

confidence: 92%

“…During HFRS-causing hantavirus infections, reduced kidney function occurs independently of the induced thrombocytopenia (22, 23). We therefore hypothesized that a comprehensive study of longitudinal antiviral B cell responses in patients infected with the Puumala strain hantavirus, in combination with matching clinical data from the same patients, could reveal important information on the effect of thrombocytopenia and kidney dysfunction for expansion of both plasmablasts and plasma cells (PBs/PCs) and CD27 − IgD − B cells in circulation, and its consequence for development of antiviral humoral immunity.…”

Section: Introductionmentioning

confidence: 99%

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The generation of plasma cells and CD27⁻IgD⁻B cells during Hantavirus infection are associated with distinct pathological findings

Kerkman

Dernstedt

Tadala

et al. 2019

Preprint

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Human hantavirus infections can cause hemorrhagic fever with renal syndrome (HFRS), major signs of the disease being thrombocytopenia and transient kidney dysfunction. By a comprehensive and longitudinal study of circulating B cells, we demonstrate that these two pathologies associate with distinct effects on the humoral immune system during HFRS. Low thrombocyte counts strongly associated with an abnormal frequency of plasmablasts in circulation, whereas kidney dysfunction was indicative of an accumulation of CD27 -B cells and plasmablasts. Finally, we provide evidence that high levels of extracellular ATP in circulation during HFRS correlates with shedding of surface CD27 on B cells via a metallomatrix proteinase-8-mediated mechanism. Since extracellular ATP is known to regulate kidney function, our study reveals a link between kidney dysfunction and the generation of CD27 -IgD -B cells, and a potential molecular target for treatment of the symptomatic phase of HFRS. Dobrava, Seol and Puumala (PUUV) strains, where PUUV is endemic to Scandinavia. To date, no efficacious treatment or vaccination regimen exists to protect against severe hantavirus infections.Well controlled human studies have shown that hantavirus infections cause aberrant activation of both innate and adaptive immunity (5)(6)(7)(8). A potent antiviral IgG-response is associated with protection from severe disease during both HPS and HFRS (9-12) and passive transfer of serum antibodies could reduce case fatality rate in a small cohort of HPS patients (13). These findings clearly demonstrate that activation of the humoral immune system and subsequent elicitation of antiviral antibodies play a central role in the control of viremia and/or pathogenesis during hantavirus infections.A recent study of HPS demonstrated that very high levels of plasmablasts (PBs) and CD27 -IgD -B cells were detected in circulation of patients (14). The rapid and extensive PB-response is similar to that reported during acute dengue virus infection and contrasts to the comparably moderate levels of PBs that are found in circulation during influenza infection or after influenza vaccination (15). An expansion of the CD27 -IgD -B cell subset has previously been shown for numerous inflammatory and infectious diseases, as well as during ageing and cancer (16-21), yet their functional role in humoral immunity remains undetermined. The CD27 -IgD -B cells resemble memory B cells, have isotype switched and hypermutated B cell receptors and therefore likely originate from T cell-dependent germinal center reactions in secondary lymphoid organs (16, 20). In systemic lupus erythematosus (SLE), an expanded population of CD27 -IgD -B cells was associated with the manifestation of nephritis in patients (16). This suggests that their detection in blood may be linked to reduced kidney function, but the cause for their expansion remains to be determined.During HFRS-causing hantavirus infections, reduced kidney function occurs independently of the induced thrombocytopenia (22, 23). We therefor...

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Section: Resultssupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

The generation of plasma cells and CD27⁻IgD⁻B cells during Hantavirus infection are associated with distinct pathological findings

Kerkman

Dernstedt

Tadala

et al. 2019

Preprint

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“…Levels of serum IL-6 increased rapidly in a short period, which could be explained by the active in ammatory storm [5,6]. In this study, we detected reduced platelets on admission and progressive decline during hospitalization, which were previously demonstrated to have a relation with severe in ammation [15,16]. Urea and creatinine rose in different degrees represented renal dysfunction because of virus invasion, hypoxaemia, hypoperfusion or original kidney diseases.…”

Section: Discussionsupporting

confidence: 64%

“…The total course from rst symptoms to death was 18±8 days with a duration of 12 (8)(9)(10)(11)(12)(13)(14)(15)(16)(17) days in hospitalization. Patients died within 8±5 days after invasive ventilation.…”

Section: Main Interventions and Complicationsmentioning

confidence: 99%

The urgency of severity and mortality risk assessments for COVID-19: A summary from death cases in Wuhan, China

Yang

Gan

Zou

et al. 2020

Preprint

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Background To investigate the clinical characteristics of 21 death cases and evaluate potential factors of disease severity and mortality risk in COVID-19. Methods Retrospective analysis was used to study the clinical data of 21 death cases with COVID-19. The assessment of disease severity and mortality risk were conducted by APACHE II, SOFA, MuLBSTA and PSI scores. Results The age was 66±14 years-old and 15 (71.4%) were men. 16 (76.2%) patients had chronic medical illnesses. 12 (57.1%) patients were overweight. Decreased lymphocytes were observed in 17 (81.0%) patients on admission. Elevated D-dimer levels were noticed in 11 (52.4%) patients and increased much more when pneumonia deteriorated. The initial APACHE II and SOFA scores demonstrated 18 (85.7%) and 13 (61.9%) patients in middle-risk levels, respectively. MuLBSTA and PSI scores after admission showed high-risk mortality in 13 (61.9%) patients. Most patients developed sequent organ failure and finally caused death. Conclusion Older, male, overweight patients, combined with chronic medical histories, continuous decreased lymphocyte proportion and increased D-dimer might have a higher risk of death. The combination of general scoring (SOFA) and pneumonia specific scoring (MuLBSTA and PSI) after admission might be more sensitive to assess the mortality risk for critical patients in COVID-19.

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“…77 Interestingly, in a cohort from Finland, the severity of thrombocytopenia was associated with the degree of inflammation and with markers of capillary leakage. 78 Thrombocytopenia does not appear to be caused by impaired thrombopoeisis. 79,80 Two recent studies characterized platelet function in patients with hantavirus infection.…”

Section: Other Viral Hemorrhagic Virusesmentioning

confidence: 99%

Thrombocytopenia and Platelet Dysfunction in Acute Tropical Infectious Diseases

Putri

Tunjungputri

Groot

et al. 2018

Semin Thromb Hemost

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Thrombocytopenia is a well-known manifestation of acute tropical infectious diseases. The role of platelets in infections has received much attention recently because of their emerging activities in modulation of inflammatory responses, host defense, and vascular integrity. However, while many studies have addressed thrombocytopenia in tropical infections, abnormalities in platelet function have been largely overlooked. This is an important research gap, as platelet dysfunction may contribute to the bleeding tendency that characterizes some tropical infections. The development of novel platelet function assays that can be used in thrombocytopenic conditions (e.g., flow cytometry assays) has contributed to important new insights in recent years. In this review, the importance of platelets in tropical infections is discussed with special emphasis on the underlying mechanisms and consequences of thrombocytopenia and platelet dysfunction in these infections. Special attention is paid to malaria, a disease characterized by microvascular obstruction in which bleeding is rare, and to infections in which bleeding is common, such as dengue, other viral hemorrhagic fevers, and the bacterial infection leptospirosis. Given the importance of platelet function abnormalities in these infections, the development of affordable assays for monitoring of platelet function in low-resource countries, as well as pharmacologic interventions to prevent or reverse platelet function abnormalities, might improve clinical care and the prognosis of these infections.

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Thrombocytopenia associates with the severity of inflammation and variables reflecting capillary leakage in Puumala Hantavirus infection, an analysis of 546 Finnish patients

Abstract: The severity of thrombocytopenia associates with the degree of inflammation and variables reflecting capillary leakage, but not with the severity of acute kidney injury in PUUV infected Finnish patients.

Cited by 30 publications

References 39 publications

The generation of plasma cells and CD27⁻IgD⁻B cells during Hantavirus infection are associated with distinct pathological findings

The generation of plasma cells and CD27⁻IgD⁻B cells during Hantavirus infection are associated with distinct pathological findings

The urgency of severity and mortality risk assessments for COVID-19: A summary from death cases in Wuhan, China

Thrombocytopenia and Platelet Dysfunction in Acute Tropical Infectious Diseases

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Thrombocytopenia associates with the severity of inflammation and variables reflecting capillary leakage in Puumala Hantavirus infection, an analysis of 546 Finnish patients

Abstract: The severity of thrombocytopenia associates with the degree of inflammation and variables reflecting capillary leakage, but not with the severity of acute kidney injury in PUUV infected Finnish patients.

Cited by 30 publications

References 39 publications

The generation of plasma cells and CD27−IgD−B cells during Hantavirus infection are associated with distinct pathological findings

The generation of plasma cells and CD27−IgD−B cells during Hantavirus infection are associated with distinct pathological findings

The urgency of severity and mortality risk assessments for COVID-19: A summary from death cases in Wuhan, China

Thrombocytopenia and Platelet Dysfunction in Acute Tropical Infectious Diseases

Contact Info

Product

Resources

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The generation of plasma cells and CD27⁻IgD⁻B cells during Hantavirus infection are associated with distinct pathological findings

The generation of plasma cells and CD27⁻IgD⁻B cells during Hantavirus infection are associated with distinct pathological findings