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1.
Pediatr Blood Cancer ; 67(12): e28745, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33009893

RESUMO

Infection from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), though mainly a respiratory disease, can impair many systems, including causing hematological complications. Lymphopenia and hypercoagulability have been reported in adults with coronavirus disease 2019 (COVID-19) and are considered markers of poor prognosis. This review summarizes the hematological findings in children with SARS-CoV-2 infection. The majority of infected children had a normal leukocyte count, while the most common white blood cell abnormality was leukopenia. Lymphopenia, which may be a marker of severe disease, was rarer in children than in adults, possibly due to their immature immune system or due to the less severe manifestation of COVID-19 in this age group. Age may have an impact, and in neonates and infants the most common abnormality was lymphocytosis. Abnormalities of red blood cells and platelets were uncommon. Anemia and hypercoagulability were reported mainly in children presenting the novel multisystem inflammatory syndrome (MIS) associated with SARS-CoV-2.


Assuntos
Anemia/sangue , Betacoronavirus/metabolismo , Infecções por Coronavirus/sangue , Linfopenia/sangue , Pandemias , Pneumonia Viral/sangue , Trombofilia/sangue , Adolescente , Anemia/epidemiologia , Anemia/imunologia , Betacoronavirus/imunologia , Biomarcadores/sangue , Plaquetas/imunologia , Plaquetas/metabolismo , Criança , Pré-Escolar , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Eritrócitos/imunologia , Eritrócitos/metabolismo , Feminino , Humanos , Lactente , Recém-Nascido , Contagem de Leucócitos , Linfopenia/epidemiologia , Linfopenia/imunologia , Masculino , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Trombofilia/epidemiologia , Trombofilia/imunologia
4.
J Cancer Res Ther ; 16(4): 731-736, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32930111

RESUMO

Background: Chronic state of inflammation is an important factor in advanced cancer which is used by tumor cells for maintaining survival and growth. Hematological parameters such as neutrophil/lymphocyte ratio (NLR), thrombocyte/lymphocyte ratio (TLR), and lymphocyte/monocyte ratio (LMR) are reliable indicators of systemic inflammation. We aimed to elucidate the effect of hematological parameters and clinical features of patients on the prognosis of advanced-stage non-small cell lung cancer (NSCLC). Methods: We included 102 Stage IV NSCLC patients who presented to the oncology clinic between 2010 and 2016. Pretreatment clinical parameters and NLR, TLR, and LMR were retrieved from the medical records. The cutoff values, calculated with receiver operating curve analysis, for NLR, LMR, and TLR were 2.5, 3, and 183, respectively. All patients were divided into two groups according to cutoff values and analyzed accordingly. Results: Median overall survival and progression-free survival were 10 and 6 months, respectively. In univariate analysis, high NLR, high TLR, and low LMR were found to be significantly associated with survival. Among clinical parameters having eastern cooperative oncology group performance score 0-1, older age (≥70 years) single metastatic disease was prognostic. In multivariate Cox regression analysis, only the number of metastatic lesions and LMR were found to be independent predictors for survival. Conclusion: Among hematological parameters, only LMR was found to be an independent predictor of survival in patients with advanced-stage NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Inflamação/sangue , Neoplasias Pulmonares/patologia , Neutrófilos/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/imunologia , Plaquetas/imunologia , Plaquetas/patologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/imunologia , Feminino , Humanos , Inflamação/patologia , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Monócitos/imunologia , Monócitos/patologia , Metástase Neoplásica , Prognóstico , Estudos Retrospectivos
5.
Front Immunol ; 11: 1962, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32849656

RESUMO

Platelets, small anucleate cells circulating in the blood, are critical mediators in haemostasis and thrombosis. Interestingly, recent studies demonstrated that platelets contain both pro-inflammatory and anti-inflammatory molecules, equipping platelets with immunoregulatory function in both innate and adaptive immunity. In the context of infectious diseases, platelets are involved in early detection of invading microorganisms and are actively recruited to sites of infection. Platelets exert their effects on microbial pathogens either by direct binding to eliminate or restrict dissemination, or by shaping the subsequent host immune response. Reciprocally, many invading microbial pathogens can directly or indirectly target host platelets, altering platelet count or/and function. In addition, microbial pathogens can impact the host auto- and alloimmune responses to platelet antigens in several immune-mediated diseases, such as immune thrombocytopenia, and fetal and neonatal alloimmune thrombocytopenia. In this review, we discuss the mechanisms that contribute to the bidirectional interactions between platelets and various microbial pathogens, and how these interactions hold relevant implications in the pathogenesis of many infectious diseases. The knowledge obtained from "well-studied" microbes may also help us understand the pathogenesis of emerging microbes, such as SARS-CoV-2 coronavirus.


Assuntos
Betacoronavirus , Plaquetas/imunologia , Plaquetas/metabolismo , Infecções por Coronavirus/imunologia , Interações Hospedeiro-Patógeno/imunologia , Pneumonia Viral/imunologia , Imunidade Adaptativa , Infecções por Coronavirus/virologia , Hemostasia , Humanos , Imunidade Inata , Inflamação/imunologia , Pandemias , Pneumonia Viral/virologia , Trombose/metabolismo
6.
Ann Hematol ; 99(10): 2315-2322, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32728937

RESUMO

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by lower platelet count resulting from immune cells-mediated platelet clearance. Tacrolimus is an immunosuppressive agent which selectively inhibits T cell activation. Whether tacrolimus plays a role in ITP remains unclear. This study aimed to investigate the effect of tacrolimus on ITP in mice. An ITP mouse model was established by injection of rat anti-mouse integrin GPIIb/CD41 immunoglobulin and treated with tacrolimus followed by isolation of peripheral blood mononuclear cells and plasma. The mRNA expression of T-bet, GATA3, and Foxp3 was measured by RT-PCR, and level of IFN-γ, IL-12p70, IL-4, IL-13, and TGF-ß in plasma was measured by ELISA. Tacrolimus inhibited antiplatelet antibody-mediated platelet clearance in ITP mouse model. Meanwhile, tacrolimus-treated ITP mice displayed a significant decrease in the mRNA expression of T-bet and plasma level of IFN-γ and IL-12p70 compared with ITP mice but without differences when compared with normal mice. Furthermore, the expression of GATA3, Foxp3, and plasma level of IL-4 and TGF-ß were upregulated in tacrolimus-treated ITP mice without significant differences to normal mice (except TGF-ß). Tacrolimus prevents antiplatelet antibody-mediated thrombocytopenia in ITP mice possibly through regulating T cell differentiations, suggesting it might be a novel approach for preventing ITP.


Assuntos
Imunossupressores/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Tacrolimo/uso terapêutico , Animais , Plaquetas/imunologia , Citocinas/biossíntese , Citocinas/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Isoanticorpos/sangue , Camundongos , Camundongos Endogâmicos C57BL , Púrpura Trombocitopênica Idiopática/genética , Púrpura Trombocitopênica Idiopática/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Organismos Livres de Patógenos Específicos , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/imunologia , Fatores de Transcrição/biossíntese , Fatores de Transcrição/genética
7.
Mol Immunol ; 124: 9-17, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32485436

RESUMO

BACKGROUND: Platelet refractoriness remains a challenging clinical dilemma although significant advancements have been made in identifying human leukocyte antigen (HLA) matched or HLA compatible units. Antiplatelet antibodies are the major risk factor for immune-mediated platelet refractoriness, yet the role of antibody-initiated complement-mediated platelet destruction remains poorly understood. STUDY DESIGN AND METHODS: Human complement-mediated opsonization and killing of platelets was assayed ex vivo using antibody-sensitized human platelets incubated with complement-sufficient human sera. A new animal model of platelet refractoriness utilizing Wistar rats transfused with human platelets is described. RESULTS: Human platelets sensitized with anti-platelet antibodies were rapidly opsonized with iC3b upon incubation in human sera. This opsonization could be completely blocked with a classical pathway complement inhibitor, PA-dPEG24. Complement activation decreased platelet viability, which was also reversible with complement inhibitor PA-dPEG24. A new rat model of platelet refractoriness was developed that demonstrated some platelet removal from the blood stream was complement mediated. CONCLUSIONS: Complement activation initiated by anti-platelet antibodies leads to complement opsonization and decreased platelet viability. A new rat model of platelet refractoriness was developed that adds a new tool for elucidating the mechanisms of platelet refractoriness.


Assuntos
Plaquetas/imunologia , Ativação do Complemento/imunologia , Modelos Animais de Doenças , Isoanticorpos/imunologia , Animais , Via Clássica do Complemento , Humanos , Masculino , Ratos , Ratos Wistar , Transplante Heterólogo
8.
Blood ; 136(10): 1169-1179, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32597954

RESUMO

COVID-19 affects millions of patients worldwide, with clinical presentation ranging from isolated thrombosis to acute respiratory distress syndrome (ARDS) requiring ventilator support. Neutrophil extracellular traps (NETs) originate from decondensed chromatin released to immobilize pathogens, and they can trigger immunothrombosis. We studied the connection between NETs and COVID-19 severity and progression. We conducted a prospective cohort study of COVID-19 patients (n = 33) and age- and sex-matched controls (n = 17). We measured plasma myeloperoxidase (MPO)-DNA complexes (NETs), platelet factor 4, RANTES, and selected cytokines. Three COVID-19 lung autopsies were examined for NETs and platelet involvement. We assessed NET formation ex vivo in COVID-19 neutrophils and in healthy neutrophils incubated with COVID-19 plasma. We also tested the ability of neonatal NET-inhibitory factor (nNIF) to block NET formation induced by COVID-19 plasma. Plasma MPO-DNA complexes increased in COVID-19, with intubation (P < .0001) and death (P < .0005) as outcome. Illness severity correlated directly with plasma MPO-DNA complexes (P = .0360), whereas Pao2/fraction of inspired oxygen correlated inversely (P = .0340). Soluble and cellular factors triggering NETs were significantly increased in COVID-19, and pulmonary autopsies confirmed NET-containing microthrombi with neutrophil-platelet infiltration. Finally, COVID-19 neutrophils ex vivo displayed excessive NETs at baseline, and COVID-19 plasma triggered NET formation, which was blocked by nNIF. Thus, NETs triggering immunothrombosis may, in part, explain the prothrombotic clinical presentations in COVID-19, and NETs may represent targets for therapeutic intervention.


Assuntos
Infecções por Coronavirus/complicações , Armadilhas Extracelulares/imunologia , Neutrófilos/imunologia , Pneumonia Viral/complicações , Trombose/complicações , Adulto , Idoso , Betacoronavirus/imunologia , Plaquetas/imunologia , Plaquetas/patologia , Proteínas Sanguíneas/imunologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infiltração de Neutrófilos , Neutrófilos/patologia , Pandemias , Peroxidase/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/patologia , Estudos Prospectivos , Trombose/imunologia , Trombose/patologia
9.
PLoS Pathog ; 16(5): e1008544, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32407390

RESUMO

Beyond their canonical roles in hemostasis and thrombosis, platelets function in the innate immune response by interacting directly with pathogens and by regulating the recruitment and activation of immune effector cells. Thrombocytopenia often coincides with neutropenia in patients with hematologic malignancies and in allogeneic hematopoietic cell transplant recipients, patient groups at high risk for invasive fungal infections. While neutropenia is well established as a major clinical risk factor for invasive fungal infections, the role of platelets in host defense against human fungal pathogens remains understudied. Here, we examined the role of platelets in murine Aspergillus fumigatus infection using two complementary approaches to induce thrombocytopenia without concurrent neutropenia. Thrombocytopenic mice were highly susceptible to A. fumigatus challenge and rapidly succumbed to infection. Although platelets regulated early conidial phagocytosis by neutrophils in a spleen tyrosine kinase (Syk)-dependent manner, platelet-regulated conidial phagocytosis was dispensable for host survival. Instead, our data indicated that platelets primarily function to maintain hemostasis and lung integrity in response to exposed fungal antigens, since thrombocytopenic mice exhibited severe hemorrhage into the airways in response to fungal challenge in the absence of overt angioinvasion. Challenge with swollen, heat-killed, conidia was lethal in thrombocytopenic hosts and could be reversed by platelet transfusion, consistent with the model that fungus-induced inflammation in platelet-depleted mice was sufficient to induce lethal hemorrhage. These data provide new insights into the role of platelets in the anti-Aspergillus host response and expand their role to host defense against filamentous molds.


Assuntos
Aspergillus fumigatus/imunologia , Plaquetas/imunologia , Transplante de Células-Tronco Hematopoéticas , Neutropenia/imunologia , Aspergilose Pulmonar/imunologia , Quimeras de Transplante/imunologia , Aloenxertos , Animais , Camundongos , Neutropenia/microbiologia , Neutropenia/patologia , Aspergilose Pulmonar/patologia , Quimeras de Transplante/microbiologia
10.
Nat Commun ; 11(1): 1939, 2020 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-32321925

RESUMO

Acetaminophen (APAP) is the main cause of acute liver failure in the West. Specific efficacious therapies for acute liver failure (ALF) are limited and time-dependent. The mechanisms that drive irreversible acute liver failure remain poorly characterized. Here we report that the recently discovered platelet receptor CLEC-2 (C-type lectin-like receptor) perpetuates and worsens liver damage after toxic liver injury. Our data demonstrate that blocking platelet CLEC-2 signalling enhances liver recovery from acute toxic liver injuries (APAP and carbon tetrachloride) by increasing tumour necrosis factor-α (TNF-α) production which then enhances reparative hepatic neutrophil recruitment. We provide data from humans and mice demonstrating that platelet CLEC-2 influences the hepatic sterile inflammatory response and that this can be manipulated for therapeutic benefit in acute liver injury. Since CLEC-2 mediated platelet activation is independent of major haemostatic pathways, blocking this pathway represents a coagulopathy-sparing, specific and novel therapy in acute liver failure.


Assuntos
Acetaminofen/efeitos adversos , Plaquetas/imunologia , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Lectinas Tipo C/imunologia , Neutrófilos/imunologia , Animais , Tetracloreto de Carbono/efeitos adversos , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Humanos , Lectinas Tipo C/genética , Fígado/efeitos dos fármacos , Fígado/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
12.
Semin Thromb Hemost ; 46(3): 302-319, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32279287

RESUMO

Thrombocytopenia is commonly associated with sepsis and infections, which in turn are characterized by a profound immune reaction to the invading pathogen. Platelets are one of the cellular entities that exert considerable immune, antibacterial, and antiviral actions, and are therefore active participants in the host response. Platelets are sensitive to surrounding inflammatory stimuli and contribute to the immune response by multiple mechanisms, including endowing the endothelium with a proinflammatory phenotype, enhancing and amplifying leukocyte recruitment and inflammation, promoting the effector functions of immune cells, and ensuring an optimal adaptive immune response. During infection, pathogens and their products influence the platelet response and can even be toxic. However, platelets are able to sense and engage bacteria and viruses to assist in their removal and destruction. Platelets greatly contribute to host defense by multiple mechanisms, including forming immune complexes and aggregates, shedding their granular content, and internalizing pathogens and subsequently being marked for removal. These processes, and the nature of platelet function in general, cause the platelet to be irreversibly consumed in the execution of its duty. An exaggerated systemic inflammatory response to infection can drive platelet dysfunction, where platelets are inappropriately activated and face immunological destruction. While thrombocytopenia may arise by condition-specific mechanisms that cause an imbalance between platelet production and removal, this review evaluates a generic large-scale mechanism for platelet depletion as a repercussion of its involvement at the nexus of responses to infection.


Assuntos
Plaquetas/imunologia , Infecções/sangue , Humanos
13.
Nat Commun ; 11(1): 1315, 2020 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-32161256

RESUMO

Myocardial ischemia is one of the leading health problems worldwide. Therapy consists of the restitution of coronary perfusion which is followed by myocardial inflammation. Platelet-neutrophil interaction is a crucial process during inflammation, yet its consequences are not fully understood. Here, we show that platelet-neutrophil complexes (PNCs) are increased in patients with acute myocardial infarction and that this is associated with increased levels of neuronal guidance protein semaphorin 7A (SEMA7A). To investigate this further, we injected WT animals with Sema7a and found increased infarct size with increased numbers of PNCs. Experiments in genetically modified animals identify Sema7a on red blood cells to be crucial for this condition. Further studies revealed that Sema7a interacts with the platelet receptor glycoprotein Ib (GPIb). Treatment with anti-Sema7a antibody protected from myocardial tissue injury. In summary, we show that Sema7a binds to platelet GPIb and enhances platelet thrombo-inflammatory activity, aggravating post-ischemic myocardial tissue injury.


Assuntos
Antígenos CD/metabolismo , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/patologia , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Semaforinas/metabolismo , Trombose/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antígenos CD/genética , Antígenos CD/imunologia , Plaquetas/imunologia , Plaquetas/metabolismo , Vasos Coronários/patologia , Modelos Animais de Doenças , Eritrócitos/imunologia , Eritrócitos/metabolismo , Feminino , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/imunologia , Proteínas Ligadas por GPI/metabolismo , Humanos , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/imunologia , Traumatismo por Reperfusão Miocárdica/sangue , Traumatismo por Reperfusão Miocárdica/imunologia , Miocárdio/patologia , Estudos Prospectivos , Semaforinas/genética , Semaforinas/imunologia , Trombose/imunologia , Adulto Jovem
14.
Transfusion ; 60(4): 847-854, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32129498

RESUMO

BACKGROUND: Anti-CD36s, developing after transfusion or during pregnancy, play an important role in immune-mediated bleeding disorders among Asian populations. Currently, little is known about the clinical relevance of anti-CD36. Here, we aimed to determine the frequency of CD36 deficiency in Thais by analyzing CD36 expression on cell surfaces and in plasma. STUDY DESIGN AND METHODS: The expression and deficiency of CD36 on platelets and monocytes were determined by flow cytometry. Mutations in the CD36 gene were analyzed by nucleotide sequencing. Soluble CD36 (sCD36) in plasma was quantified with enzyme-linked immunosorbent assay. RESULTS: Fifteen of 700 blood donors (2.14%) were identified as CD36 deficient. The frequencies of Type I and II CD36 deficiency were 0.43% and 1.71%, respectively. Type I individuals exhibited c.1163A > T, c.429 + 4insG, and c.1156C > T. Type II individuals exhibited c.879 T > C, c.329-330delAC, c.818 + 108delAACT, c.1125 + 13C > A, and c.1163A > T. CD36 on donor platelets (n = 685) showed a wide distribution of expression levels (mean fluorescence intensity, 16.71 ± 8.68). In the normal phenotype (n = 14), sCD36 concentration was 58.84 ± 11.68 ng/mL, which was significantly correlated with platelet CD36 expression (r2 = 0.8551). In Type II-deficient individuals (n = 6), a similar sCD36 concentration was detected (53.67 ± 8.17 ng/mL). However, sCD36 could not be detected in Type I individuals (n = 3). CONCLUSION: CD36 Type I deficiency was found, indicating the potential for immune-mediated platelet disorders in Thais. However, the underlying mutations differed from those reported in Japan and China. Interestingly, sCD36 could not be detected in plasma of Type I-deficient individuals. This finding may lead to the use of plasma to identify individuals at risk and to allow screening of large cohorts.


Assuntos
Antígenos de Superfície/análise , Doadores de Sangue , Plaquetas/imunologia , Antígenos CD36/deficiência , Plasma/imunologia , Grupo com Ancestrais do Continente Asiático , Antígenos CD36/análise , Antígenos CD36/sangue , Antígenos CD36/genética , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Humanos , Monócitos/imunologia , Mutação , Análise de Sequência de DNA , Tailândia/epidemiologia
16.
Sci Adv ; 6(11): eaaz1580, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32195350

RESUMO

Dendritic cells (DCs) are adept at cross-presentation and initiation of antigen-specific immunity. Clinically, however, DCs produced by in vitro differentiation of monocytes in the presence of exogenous cytokines have been met with limited success. We hypothesized that DCs produced in a physiological manner may be more effective and found that platelets activate a cross-presentation program in peripheral blood monocytes with rapid (18 hours) maturation into physiological DCs (phDCs). Differentiation of monocytes into phDCs was concomitant with the formation of an "adhesion synapse," a biophysical junction enriched with platelet P-selectin and monocyte P-selectin glycoprotein ligand 1, followed by intracellular calcium fluxing and nuclear localization of nuclear factor κB. phDCs were more efficient than cytokine-derived DCs in generating tumor-specific T cell immunity. Our findings demonstrate that platelets mediate a cytokine-independent, physiologic maturation of DC and suggest a novel strategy for DC-based immunotherapies.


Assuntos
Apresentação do Antígeno , Plaquetas/imunologia , Sinalização do Cálcio/imunologia , Diferenciação Celular/imunologia , Células Dendríticas/imunologia , Monócitos/imunologia , Selectina-P/imunologia , Animais , Antígenos de Neoplasias/genética , Antígenos de Neoplasias/imunologia , Sinalização do Cálcio/genética , Diferenciação Celular/genética , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/imunologia , Camundongos , Camundongos Transgênicos , NF-kappa B/genética , NF-kappa B/imunologia , Selectina-P/genética , Linfócitos T/imunologia
17.
Platelets ; 31(3): 315-321, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32054377

RESUMO

Diagnosis of immune thrombocytopenia (ITP) and prediction of response to therapy remain significant and constant challenges in hematology. In patients who present with ITP, the platelet count is frequently used as a surrogate marker for disease severity, and so often determines the need for therapy. Although there is a clear link between thrombocytopenia and hemostasis, a direct correlation between the extent of thrombocytopenia and bleeding symptoms, especially at lower platelet counts is lacking. Thus, bleeding in ITP is heterogeneous, unpredictable, and nearly always based on a multitude of risk factors, beyond the platelet count. The development of an evidence-based, validated risk stratification model for ITP treatment is a major goal in the ITP community and this review discusses new laboratory approaches to evaluate the various pathobiologies of ITP that may inform such a model.


Assuntos
Suscetibilidade a Doenças , Púrpura Trombocitopênica Idiopática/etiologia , Pesquisa/tendências , Animais , Biomarcadores , Plaquetas/imunologia , Plaquetas/metabolismo , Plaquetas/patologia , Suscetibilidade a Doenças/imunologia , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Megacariócitos/imunologia , Megacariócitos/metabolismo , Megacariócitos/patologia , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/metabolismo , Púrpura Trombocitopênica Idiopática/terapia
18.
Clin Exp Immunol ; 201(1): 14-24, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32048277

RESUMO

Toll-like receptors (TLRs) are evolutionarily conserved receptors essential for the host defence against pathogens. Both immune and non-immune cells can express TLRs, although at different levels. Systemic sclerosis (SSc) is a chronic disease in which autoimmunity, dysregulated profibrotic mediator release and activation of fibroblasts lead to dysregulated collagen deposition and fibrosis. There is now increasing knowledge that the innate immune system and, in particular, TLRs take a part in SSc pathogenesis. The list of endogenous ligands that can stimulate TLRs in SSc is growing: these ligands represent specific danger-associated molecular patterns (DAMPs), involved either in the initiation or the perpetuation of inflammation, and in the release of factors that sustain the fibrotic process or directly stimulate the cells that produce collagen and the endothelial cells. This review reports evidences concerning TLR signalling involvement in SSc. We report the new DAMPs, as well as the TLR-linked pathways involved in disease, with emphasis on type I interferon signature in SSc, the role of plasmacytoid dendritic cells (pDCs) and platelets. The dissection of the contribution of all these pathways to disease, and their correlation with the disease status, as well as their values as prognostic tools, can help to plan timely intervention and design new drugs for more appropriate therapeutic strategies.


Assuntos
Plaquetas/imunologia , Células Dendríticas/imunologia , Plasmócitos/imunologia , Escleroderma Sistêmico/imunologia , Receptores Toll-Like/imunologia , Animais , Plaquetas/patologia , Células Dendríticas/patologia , Humanos , Plasmócitos/patologia , Escleroderma Sistêmico/diagnóstico , Escleroderma Sistêmico/patologia
19.
PLoS Pathog ; 16(2): e1008334, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32101596

RESUMO

Influenza A virus (IAV) infection is a complicated process. After IAVs spread to the lung, extensive pro-inflammatory cytokines and chemokines are released, which largely determine the outcome of infection. Using a single-cell RNA sequencing (scRNA-seq) assay, we systematically and sequentially analyzed the transcriptome of more than 16,000 immune cells in the pulmonary tissue of infected mice, and demonstrated that two waves of pro-inflammatory factors were released. A group of IAV-infected PD-L1+ neutrophils were the major contributor to the first wave at an earlier stage (day 1-3 post infection). Notably, at a later stage (day 7 post infection) when IAV was hardly detected in the immune cells, a group of platelet factor 4-positive (Pf4+)-macrophages generated another wave of pro-inflammatory factors, which were probably the precursors of alveolar macrophages (AMs). Furthermore, single-cell signaling map identified inter-lineage crosstalk between different clusters and helped better understand the signature of PD-L1+ neutrophils and Pf4+-macrophages. Our data characteristically clarified the infiltrated immune cells and their production of pro-inflammatory factors during the immunopathogenesis development, and deciphered the important mechanisms underlying IAV-driven inflammatory reactions in the lung.


Assuntos
Vírus da Influenza A/imunologia , Pulmão/imunologia , Macrófagos Alveolares/imunologia , Animais , Plaquetas/imunologia , Quimiocinas/imunologia , Citocinas/imunologia , Feminino , Humanos , Inflamação/patologia , Vírus da Influenza A Subtipo H1N1/imunologia , Vírus da Influenza A/metabolismo , Vírus da Influenza A/patogenicidade , Influenza Humana/virologia , Macrófagos/imunologia , Macrófagos Alveolares/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neutrófilos/imunologia , Infecções por Orthomyxoviridae/imunologia , Análise de Sequência de RNA/métodos , Transdução de Sinais/imunologia , Análise de Célula Única/métodos
20.
Ann Thorac Cardiovasc Surg ; 26(5): 248-255, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-32074540

RESUMO

BACKGROUND: Complete blood cell count (CBC)-derived inflammatory biomarkers are widely used as prognostic parameters for various malignancies, but the best predictive biomarker for early-stage non-small-cell lung cancer (NSCLC) is unclear. We retrospectively analyzed early-stage NSCLC patients to investigate predictive effects of preoperative CBC-derived inflammatory biomarkers. PATIENTS AND METHODS: We selected 311 consecutive patients with pathological stage IA NSCLC surgically resected from April 2006 to December 2012. Univariate and multivariate Cox proportional analyses of recurrence-free survival (RFS) were used to test the preoperative systemic immune inflammation index (SII), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and monocyte-lymphocyte ratio (MLR). RESULTS: Preoperative high MLR levels were significantly associated with patient sex, smoking status, and postoperative recurrence (p <0.0001, p = 0.0307, and p = 0.0146, respectively), and preoperative high SII levels were significantly correlated with postoperative recurrence (p = 0.0458). Neither NLR nor PLR were associated with any related factors. Only preoperative MLR levels (p = 0.0269) were identified as an independent predictor of shorter RFS. The relative risk (RR) for preoperative high MLR level versus low level patients was 2.259 (95% confidence interval [CI]: 1.094-5.000). Five-year RFS rates in patients with preoperatively high MLR levels were significantly lower than in those with low MLR levels (82.21% vs. 92.05%, p = 0.0062). In subgroup analysis by tumor size and MLR level, the high MLR level subgroup with tumors >2 cm had significantly shorter RFS than other subgroups (p = 0.0289). CONCLUSIONS: The preoperative MLR level is the optimal predictor of recurrence in patients with pathological stage IA NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/imunologia , Inflamação/imunologia , Neoplasias Pulmonares/imunologia , Linfócitos/imunologia , Monócitos/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Plaquetas/imunologia , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Neutrófilos/imunologia , Contagem de Plaquetas , Pneumonectomia , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Carga Tumoral
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