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1.
Rheumatology (Oxford) ; 60(7): 3144-3155, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33280020

RESUMO

OBJECTIVE: Sjögren syndrome in children is a poorly understood autoimmune disease. We aimed to describe the clinical and diagnostic features of children diagnosed with Sjögren syndrome and explore how the 2016 ACR/EULAR classification criteria apply to this population. METHODS: An international workgroup retrospectively collected cases of Sjögren syndrome diagnosed under 18 years of age from 23 centres across eight nations. We analysed patterns of symptoms, diagnostic workup, and applied the 2016 ACR/EULAR classification criteria. RESULTS: We identified 300 children with Sjögren syndrome. The majority of patients n = 232 (77%) did not meet 2016 ACR/EULAR classification criteria, but n = 110 (37%) did not have sufficient testing done to even possibly achieve the score necessary to meet criteria. Even among those children with all criteria items tested, only 36% met criteria. The most common non-sicca symptoms were arthralgia [n = 161 (54%)] and parotitis [n = 140 (47%)] with parotitis inversely correlating with age. CONCLUSION: Sjögren syndrome in children can present at any age. Recurrent or persistent parotitis and arthralgias are common symptoms that should prompt clinicians to consider the possibility of Sjögren syndrome. The majority of children diagnosed with Sjögren syndromes did not meet 2016 ACR/EULAR classification criteria. Comprehensive diagnostic testing from the 2016 ACR/EULAR criteria are not universally performed. This may lead to under-recognition and emphasizes a need for further research including creation of paediatric-specific classification criteria.


Assuntos
Artralgia/fisiopatologia , Parotidite/fisiopatologia , Síndrome de Sjogren/fisiopatologia , Adolescente , Idade de Início , Anticorpos Antinucleares/imunologia , Criança , Pré-Escolar , Estudos de Coortes , Síndromes do Olho Seco/fisiopatologia , Feminino , Humanos , Hipergamaglobulinemia/fisiopatologia , Lactente , Linfopenia/fisiopatologia , Masculino , Neutropenia/fisiopatologia , Fator Reumatoide/imunologia , Síndrome de Sjogren/diagnóstico , Síndrome de Sjogren/imunologia , Trombocitopenia/fisiopatologia , Xerostomia/fisiopatologia
2.
J Med Virol ; 92(6): 577-583, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32162702

RESUMO

The aim of this study was to analyze the clinical data, discharge rate, and fatality rate of COVID-19 patients for clinical help. The clinical data of COVID-19 patients from December 2019 to February 2020 were retrieved from four databases. We statistically analyzed the clinical symptoms and laboratory results of COVID-19 patients and explained the discharge rate and fatality rate with a single-arm meta-analysis. The available data of 1994 patients in 10 literatures were included in our study. The main clinical symptoms of COVID-19 patients were fever (88.5%), cough (68.6%), myalgia or fatigue (35.8%), expectoration (28.2%), and dyspnea (21.9%). Minor symptoms include headache or dizziness (12.1%), diarrhea (4.8%), nausea and vomiting (3.9%). The results of the laboratory showed that the lymphocytopenia (64.5%), increase of C-reactive protein (44.3%), increase of lactic dehydrogenase (28.3%), and leukocytopenia (29.4%) were more common. The results of single-arm meta-analysis showed that the male took a larger percentage in the gender distribution of COVID-19 patients 60% (95% CI [0.54, 0.65]), the discharge rate of COVID-19 patients was 52% (95% CI [0.34,0.70]), and the fatality rate was 5% (95% CI [0.01,0.11]).


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/fisiopatologia , Pandemias , Alta do Paciente/estatística & dados numéricos , Pneumonia Viral/epidemiologia , Pneumonia Viral/fisiopatologia , Betacoronavirus/patogenicidade , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , COVID-19 , China/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/mortalidade , Tosse/sangue , Tosse/diagnóstico , Tosse/fisiopatologia , Dispneia/sangue , Dispneia/diagnóstico , Dispneia/fisiopatologia , Feminino , Febre/sangue , Febre/diagnóstico , Febre/fisiopatologia , Humanos , Incidência , Linfopenia/sangue , Linfopenia/diagnóstico , Linfopenia/fisiopatologia , Masculino , Pneumonia Viral/diagnóstico , Pneumonia Viral/mortalidade , SARS-CoV-2 , Fatores Sexuais , Análise de Sobrevida
3.
J Med Virol ; 92(6): 568-576, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32134116

RESUMO

By 27 February 2020, the outbreak of coronavirus disease 2019 (COVID-19) caused 82 623 confirmed cases and 2858 deaths globally, more than severe acute respiratory syndrome (SARS) (8273 cases, 775 deaths) and Middle East respiratory syndrome (MERS) (1139 cases, 431 deaths) caused in 2003 and 2013, respectively. COVID-19 has spread to 46 countries internationally. Total fatality rate of COVID-19 is estimated at 3.46% by far based on published data from the Chinese Center for Disease Control and Prevention (China CDC). Average incubation period of COVID-19 is around 6.4 days, ranges from 0 to 24 days. The basic reproductive number (R0 ) of COVID-19 ranges from 2 to 3.5 at the early phase regardless of different prediction models, which is higher than SARS and MERS. A study from China CDC showed majority of patients (80.9%) were considered asymptomatic or mild pneumonia but released large amounts of viruses at the early phase of infection, which posed enormous challenges for containing the spread of COVID-19. Nosocomial transmission was another severe problem. A total of 3019 health workers were infected by 12 February 2020, which accounted for 3.83% of total number of infections, and extremely burdened the health system, especially in Wuhan. Limited epidemiological and clinical data suggest that the disease spectrum of COVID-19 may differ from SARS or MERS. We summarize latest literatures on genetic, epidemiological, and clinical features of COVID-19 in comparison to SARS and MERS and emphasize special measures on diagnosis and potential interventions. This review will improve our understanding of the unique features of COVID-19 and enhance our control measures in the future.


Assuntos
Controle de Doenças Transmissíveis/organização & administração , Infecções por Coronavirus/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Síndrome Respiratória Aguda Grave/epidemiologia , Antivirais/uso terapêutico , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , COVID-19 , Vacinas contra COVID-19 , China/epidemiologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/prevenção & controle , Infecções por Coronavirus/terapia , Infecções por Coronavirus/transmissão , Humanos , Imunização Passiva/métodos , Linfopenia/fisiopatologia , Linfopenia/virologia , Coronavírus da Síndrome Respiratória do Oriente Médio/efeitos dos fármacos , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Pandemias/prevenção & controle , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/prevenção & controle , Pneumonia Viral/transmissão , Prevalência , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/efeitos dos fármacos , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/patogenicidade , SARS-CoV-2 , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Síndrome Respiratória Aguda Grave/prevenção & controle , Síndrome Respiratória Aguda Grave/transmissão , Análise de Sobrevida , Trombocitopenia/fisiopatologia , Trombocitopenia/virologia , Vacinas Virais/biossíntese , Soroterapia para COVID-19
4.
Eur J Clin Invest ; 50(10): e13351, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32681526

RESUMO

BACKGROUNDS: More paediatric-confirmed cases have been reported with the global pandemic of COVID-19. This study aims to summarize the key points and supply suggestions on screening paediatric COVID-19 patients more appropriately. MATERIALS AND METHODS: We retrospectively included paediatric patients who have accepted SARS-CoV-2 RT-PCR testing in Children's Hospital of Chongqing Medical University (30 January 2020 to 13 February 2020) and compared them with paediatric-confirmed COVID-19 cases. Besides, a review was carried out by analysing all current literature about laboratory-confirmed paediatric cases with COVID-19. RESULTS: There were 46 suspected cases included in the descriptive study. The results of SARS-CoV-2 RT-PCR testing were all negative. Compared with paediatric-confirmed cases, the incidence of epidemic history was lower in suspected cases (P < .001). The rate of fever (P < .001), cough (P < .001), headache or dizziness (P < .001), vomiting (P < .001) and abdominal discomfort or distention (P = .01) were more observed in the included suspected children. There were more children having decreased WBC count in the confirmed group. In the literature review, twenty-nine studies were obtained with 488 paediatric COVID-19 cases. 88.6% of them had epidemiological history. Cough and fever were the most common symptoms. Compared with older patients, the incidence of fever, respiratory symptoms, lethargy and headache or dizziness was lower, while gastrointestinal symptoms were reported more. CONCLUSIONS: Children with a history of close contact with confirmed cases, manifested as cough and fever should be paid more attention to after excluding infection of other common pathogens. Atypical symptoms should not be over-emphasized in screening paediatric COVID-19. More studies are needed for guiding efficient recognition in paediatric COVID-19.


Assuntos
Infecções por Coronavirus/diagnóstico , Pneumonia Viral/diagnóstico , Dor Abdominal/fisiopatologia , Betacoronavirus , COVID-19 , Teste para COVID-19 , Criança , Pré-Escolar , Técnicas de Laboratório Clínico , Infecções por Coronavirus/fisiopatologia , Tosse/fisiopatologia , Tontura/fisiopatologia , Feminino , Febre/fisiopatologia , Cefaleia/fisiopatologia , Humanos , Lactente , Pulmão/diagnóstico por imagem , Linfopenia/fisiopatologia , Masculino , Programas de Rastreamento , Pandemias , Pneumonia Viral/fisiopatologia , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Medição de Risco , SARS-CoV-2 , Vômito/fisiopatologia
5.
Monaldi Arch Chest Dis ; 90(4)2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33169598

RESUMO

COVID-19 is a pandemic with over 5 million cases worldwide. The disease has imposed a huge burden on health resources. Evaluation of clinical and epidemiological profiles of such patients can help in understanding and managing the outbreak more efficiently. This study was a prospective observational analysis of 200 diagnosed COVID-19 patients admitted to a tertiary care center from 20th march to 8th May 2020. All these patients were positive for COVID-19 by an oro-nasopharyngeal swab-rtPCR based testing. Analyses of demographic factors, clinical characteristics, comorbidities, laboratory parameters, and the outcomes were performed. The mean age of the population was 40 years with a slight male predominance (116 patients out of 200, 58%). A majority of the patients (147, 73.5 %) were symptomatic, with fever being the most common symptom (109, 54.5%), followed by cough (91, 45.5%). An older age, presence of symptoms and their duration, leukocytosis, a high quick SOFA score, a high modified SOFA score, need for ventilator support, an AST level more than 3 times the upper limit of normal (ULN), and a serum creatinine level of 2 mg/dl or greater were at a significantly higher risk of ICU admission and mortality. Presence of diabetes mellitus, AST > three times ULN, serum creatinine 2 mg/dl or higher, and a qSOFA score of 1 or higher were all associated with significantly greater odds of critical care requirement. Triage and severity assessment helps in deciding the requirement for a hospital stay and ICU admission for COVID-19 which can easily be done using clinical and laboratory parameters. A mild, moderate and severe category approach with defined criteria and treatment guidelines will help in judicious utilization of health-care resources, especially for developing countries like India.   *Other members of the Safdarjung Hospital COVID-19 working group: Balvinder Singh (Microbiology), MK Sen (Pulmonary Medicine), Shibdas Chakrabarti (Pulmonary Medicine), NK Gupta (Pulmonary medicine), AJ Mahendran (Pulmonary Medicine), Ramesh Meena (Medicine), G Usha (Anaesthesiology), Santvana Kohli (Anaesthesiology), Sahil Diwan (Anaesthesiology), Rushika Saksena (Microbiology), Vikramjeet Dutta (Microbiology), Anupam Kr Anveshi (Microbiology).


Assuntos
Infecções por Coronavirus/sangue , Infecções por Coronavirus/fisiopatologia , Pneumonia Viral/sangue , Pneumonia Viral/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Anemia/sangue , Aspartato Aminotransferases/sangue , Betacoronavirus , COVID-19 , Criança , Pré-Escolar , Comorbidade , Doença da Artéria Coronariana/epidemiologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/terapia , Tosse/fisiopatologia , Creatinina/sangue , Diabetes Mellitus/epidemiologia , Feminino , Febre/fisiopatologia , Humanos , Hipertensão/epidemiologia , Hipóxia/fisiopatologia , Índia/epidemiologia , Lactente , Recém-Nascido , Unidades de Terapia Intensiva , Tempo de Internação , Contagem de Leucócitos , Leucocitose/sangue , Linfopenia/sangue , Linfopenia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Mialgia/fisiopatologia , Escores de Disfunção Orgânica , Pandemias , Faringite/fisiopatologia , Contagem de Plaquetas , Pneumonia Viral/mortalidade , Pneumonia Viral/terapia , Estudos Prospectivos , Respiração Artificial , SARS-CoV-2 , Taquipneia/fisiopatologia , Centros de Atenção Terciária , Fatores de Tempo , Tuberculose/epidemiologia , Adulto Jovem
6.
J Immunol ; 198(10): 3803-3808, 2017 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-28389590

RESUMO

Glycogen storage disease type 1b (GSD-1b) is an autosomal-recessive disease caused by mutation of glucose-6-phosphate transporter and characterized by altered glycogen/glucose homeostasis. A higher frequency of autoimmune diseases has been observed in GSD-1b patients, but the molecular determinants leading to this phenomenon remain unknown. To address this question, we investigated the effect of glucose-6-phosphate transporter mutation on immune cell homeostasis and CD4+ T cell functions. In GSD-1b subjects, we found lymphopenia and a reduced capacity of T cells to engage glycolysis upon TCR stimulation. These phenomena associated with reduced expression of the FOXP3 transcription factor, lower suppressive function in peripheral CD4+CD25+FOXP3+ regulatory T cells, and an impaired capacity of CD4+CD25- conventional T cells to induce expression of FOXP3 after suboptimal TCR stimulation. These data unveil the metabolic determinant leading to an increased autoimmunity risk in GSD-1b patients.


Assuntos
Autoimunidade , Doença de Depósito de Glicogênio Tipo I/imunologia , Doença de Depósito de Glicogênio Tipo I/metabolismo , Glicólise , Linfócitos T Reguladores/imunologia , Adolescente , Adulto , Antiporters/genética , Antiporters/metabolismo , Linfócitos T CD4-Positivos/imunologia , Criança , Pré-Escolar , Feminino , Fatores de Transcrição Forkhead/genética , Fatores de Transcrição Forkhead/metabolismo , Doença de Depósito de Glicogênio Tipo I/fisiopatologia , Homeostase , Humanos , Lactente , Linfopenia/imunologia , Linfopenia/fisiopatologia , Masculino , Proteínas de Transporte de Monossacarídeos/genética , Proteínas de Transporte de Monossacarídeos/metabolismo , Mutação , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Adulto Jovem
7.
Int J Gynecol Cancer ; 28(8): 1553-1559, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30247248

RESUMO

OBJECTIVE: The aim of this study was to investigate the prognostic significance of pretreatment and posttreatment lymphopenia in locally advanced squamous cell carcinoma (SCC) cervical cancer patients treated with definitive chemoradiotherapy (ChRT). METHODS: Data from 95 patients with SCC were retrospectively analyzed. Relationships between pretreatment or posttreatment lymphopenia and patient or tumor characteristics, and overall survival (OS) and disease-free survival (DFS) were evaluated. RESULTS: Median follow-ups for the entire cohort and survivors were 68 months (range, 3-133 months) and 88 months (range, 22-133 months), respectively. Ten patients (11%) exhibited pretreatment lymphopenia, whereas 58 patients (61%) exhibited posttreatment lymphopenia. Median pretreatment total lymphocyte counts decreased from 2029 cells/µL to 506 cells/µL 2 months after ChRT (P < 0.001). The 5-year OS and DFS rates were significantly higher in patients without pretreatment lymphopenia compared with patients with pre-retreatment lymphopenia (61% vs 20% [P < 0.001], 55% vs 20% [P < 0.001]). Patients without posttreatment lymphopenia had significantly higher 5-year OS and DFS rates than their counterparts (70% vs 46% [P = 0.02], 70% vs 39% [P = 0.004]). Complete response (CR) was observed in significantly fewer patients with pretreatment lymphopenia than in those without, after ChRT. Patients with posttreatment lymphopenia had higher rates of lymph node metastasis (P = 0.001) and lower posttreatment CR rates (P = 0.01) versus patients without posttreatment lymphopenia. In univariate analysis, International Federation of Gynecology and Obstetrics stage, tumor size, lymph node metastasis, and treatment response were prognostic for OS and DFS. In multivariate analysis, pretreatment lymphopenia, lymph node metastasis, and treatment response were independent predictors of OS and DFS. Age was predictive of OS. Tumor size was prognostic for DFS. CONCLUSIONS: Pretreatment lymphopenia and posttreatment lymphopenia are associated with worse treatment response in patients given ChRT for cervical SCC. Pretreatment lymphopenia is predictive for OS and DFS. Therapeutic strategies including pretreatment or posttreatment immune preservation or modulation may improve response rates and survival in women with cervical SCC.


Assuntos
Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/terapia , Cisplatino/administração & dosagem , Linfopenia/fisiopatologia , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/administração & dosagem , Braquiterapia , Carcinoma de Células Escamosas/patologia , Quimiorradioterapia , Intervalo Livre de Doença , Feminino , Humanos , Linfopenia/sangue , Linfopenia/patologia , Pessoa de Meia-Idade , Prognóstico , Radioterapia Conformacional , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/patologia
8.
Blood ; 124(10): 1622-5, 2014 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-25075129

RESUMO

XRCC4-like factor (XLF/Cernunnos) is a component of the nonhomologous end-joining (NHEJ) pathway of double-strand DNA break repair. XLF-deficient patients develop a severe progressive lymphocytopenia. Although NHEJ is required for V(D)J recombination and lymphocyte development, XLF-deficient mice have normal V(D)J recombination, highlighting the need for an alternative mechanism for the lymphocytopenia. Here, we report that XLF-deficient mice recapitulate the age-dependent lymphocytopenia of patients. We show that XLF deficiency leads to premature aging of hematopoietic stem cells (HSCs), measured by decreased functional capacity in transplantation assays, preferential myeloid reconstitution, and reduced self-renewal at a young age. We propose that premature aging of HSCs, together with previously reported defects in class-switch recombination and memory immune response, underlies the progressive and severe lymphocytopenia in XLF-deficient patients in the absence of measurable V(D)J recombination defects.


Assuntos
Proteínas de Ligação a DNA/genética , Células-Tronco Hematopoéticas/fisiologia , Linfopenia/genética , Envelhecimento/genética , Envelhecimento/imunologia , Animais , Células Cultivadas , Senescência Celular/genética , Senescência Celular/imunologia , Progressão da Doença , Linfopenia/fisiopatologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
11.
Clin Sci (Lond) ; 127(10): 589-602, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24863428

RESUMO

Lymphocytopenia is associated with an adverse prognosis in heart failure (HF). The present study investigated whether lymphocytopenia results from activated lymphocyte autophagy/apoptosis, which reflects haemodynamic inefficiency and functional aerobic impairment in patients with HF. One hundred and twenty-seven patients with HF were divided into three groups: HF with non- (lymphocytes ≥2000 cells/µl; n=45), mild (lymphocytes between ≥1500 cells/µl and <2000 cells/µl; n=39) and severe (lymphocytes <1500 cells/µl; n=43) lymphocytopenia. Lymphocyte autophagy/apoptosis, ventilatory/haemodynamic efficiencies and generic/disease-specific quality of life were analysed in these patients with HF and 35 normal counterparts. The results demonstrated that patients with HF with severe lymphocytopenia had (i) increased G-protein-coupled receptor kinase-2 (GRK-2) levels, (ii) lower mammalian target of rapamycin (mTOR) levels with higher lysosome-associated membrane protein-2 (LAMP-2) expression and Acridine Orange (AO) staining, (iii) lower mitochondrial transmembrane potential with higher caspase-3 activation and phosphatidylserine (PS) exposure, and (iv) greater extents of adrenaline (epinephrine)-induced apoptosis in lymphocytes, and higher plasma noradrenaline (norepinephrine)/adrenaline, myeloperoxidase and interleukin-6 concentrations than patients with HF without lymphocytopenia and normal counterparts did. Moreover, lymphocyte caspase-3 activation was an effect modifier, which modulated the correlation status between lymphocyte count and GRK-2 level. Lymphocyte count was positively correlated with peak cardiac output and peak oxygen consumption (VO2peak) in patients with HF. In addition, HF with lymphocytopenia was accompanied by lower Short Form-36 physical/mental component scores and increased Minnesota Living with Heart Failure Questionnaire scores. Therefore, we conclude that increased sympathetic activation and oxidative stress/pro-inflammatory status cause lymphocytopenia by activating programmed lymphocyte death in patients with HF. Moreover, a low lymphocyte count correlates with reduced haemodynamics and aerobic capacity, which reflects poor generic/disease-specific quality of life in patients with HF.


Assuntos
Apoptose/fisiologia , Autofagia/fisiologia , Insuficiência Cardíaca/fisiopatologia , Hemodinâmica/fisiologia , Linfócitos/fisiologia , Consumo de Oxigênio/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Catecolaminas/sangue , Citocinas/sangue , Eritropoetina/sangue , Feminino , Quinase 2 de Receptor Acoplado a Proteína G/sangue , Insuficiência Cardíaca/sangue , Humanos , Linfócitos/metabolismo , Linfopenia/sangue , Linfopenia/fisiopatologia , Proteína 2 de Membrana Associada ao Lisossomo/sangue , Masculino , Potencial da Membrana Mitocondrial/fisiologia , Pessoa de Meia-Idade , Peróxidos/sangue , Qualidade de Vida , Análise de Regressão , Inquéritos e Questionários , Serina-Treonina Quinases TOR/sangue
12.
Int Immunol ; 23(2): 75-88, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21266499

RESUMO

Fas-deficient mice (Fas(lpr/lpr)) and humans have profoundly dysregulated T lymphocyte homeostasis, which manifests as an accumulation of CD4(+) and CD8(+) T cells as well as an unusual population of CD4(-)CD8(-)TCRαß(+) T cells. To date, no unifying model has explained both the increased T-cell numbers and the origin of the CD4(-)CD8(-)TCRαß(+) T cells. As Fas(lpr/lpr) mice raised in a germ-free environment still manifest lymphadenopathy, we considered that this process is primarily driven by recurrent low-avidity TCR signaling in response to self-peptide/MHC as occurs during homeostatic proliferation. In these studies, we developed two independent systems to decrease the number of self-peptide/MHC contacts. First, expression of MHC class I was reduced in OT-I TCR transgenic mice. Although OT-I Fas(lpr/lpr) mice did not develop lymphadenopathy characteristic of Fas(lpr/lpr) mice, in the absence of MHC class I, OT-I Fas(lpr/lpr) T cells accumulated as both CD8(+) and CD4(-)CD8(-) T cells. In the second system, re-expression of ß(2)m limited to thymic cortical epithelial cells of Fas(lpr/lpr) ß(2)m-deficient mice yielded a model in which polyclonal CD8(+) thymocytes entered a peripheral environment devoid of MHC class I. These mice accumulated significantly greater numbers of CD4(-)CD8(-)TCRαß(+) T cells than conventional Fas(lpr/lpr) mice. Thus, Fas shapes the peripheral T-cell repertoire by regulating the survival of a subset of T cells proliferating in response to limited self-peptide/MHC contacts.


Assuntos
Antígenos de Histocompatibilidade Classe I/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T/citologia , Linfócitos T/imunologia , Receptor fas/imunologia , Animais , Antígenos CD5/imunologia , Proliferação de Células , Feminino , Ativação Linfocitária , Linfopenia/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Subpopulações de Linfócitos T/imunologia
14.
J Clin Immunol ; 31(5): 744-51, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21671128

RESUMO

T cell chemotaxis to sphingosine 1-phosphate (S1P) and the chemokines CCL21 and CCL5 was studied in ten adults with T lymphocytopenia, other immunological abnormalities (nine of ten), and frequent bacterial infections (seven of ten). Mean chemotactic responses to S1P of CD4 T cells from CD4 T lymphocytopenic patients and of CD8 T cells from CD8 T lymphocytopenic patients were significantly lower than those of healthy matched controls. Chemotaxis to CCL21 was lower than that of controls for CD4 T cells of three CD4 T lymphocytopenic patients and for CD8 T cells of three CD8 T lymphocytopenic patients, but none of the T cells of patients had diminished chemotaxis to CCL5. Defective T cell chemotactic responses to S1P and some chemokines may lead to subset-selective abnormal T cell trafficking and chronic T cell lymphocytopenia.


Assuntos
Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Linfopenia/imunologia , Receptores de Lisoesfingolipídeo/metabolismo , Subpopulações de Linfócitos T/metabolismo , Adulto , Idoso , Autoanticorpos/sangue , Infecções Bacterianas , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/patologia , Células Cultivadas , Quimiocina CCL21/imunologia , Quimiocina CCL5/imunologia , Quimiotaxia , Humanos , Imunoglobulina M/sangue , Linfopenia/diagnóstico , Linfopenia/patologia , Linfopenia/fisiopatologia , Lisofosfolipídeos/imunologia , Masculino , Pessoa de Meia-Idade , Receptores CCR7/genética , Receptores CCR7/imunologia , Receptores CCR7/metabolismo , Receptores de Lisoesfingolipídeo/genética , Receptores de Lisoesfingolipídeo/imunologia , Recidiva , Esfingosina/análogos & derivados , Esfingosina/imunologia , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/patologia
15.
Blood ; 114(18): 3831-40, 2009 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-19704119

RESUMO

Lymphopenia enhances the effectiveness of adoptive immunotherapy by facilitating expansion of transferred T cells but also limits the T-cell repertoire available to mediate immune responses and, in humans, is associated with chronic immune dysfunction. Previous studies concluded that lymphopenia augments adoptive immunotherapy by diminishing Tregs and increasing homeostatic cytokines. We sought to determine whether targeted therapies that replicate the physiology of lymphopenia in lymphoreplete hosts could provide a similarly supportive milieu. Pmel-1 T cells were transferred to B16-bearing lymphopenic versus lymphoreplete mice receiving alphaCD25 and/or recombinant human interleukin-7. Although CD25-based Treg depletion was inefficient because of peripheral expansion of CD4+CD25-FOXP3+ cells, outcomes were better in alphaCD25-treated lymphoreplete hosts than in lymphopenic hosts, and adoptive immunotherapy was most effective in lymphoreplete hosts receiving alphaCD25 plus recombinant human interleukin-7. Lymphopenic hosts supported increased proliferation of adoptively transferred antigen-specific T cells, but cells transferred to lymphoreplete recipients receiving targeted therapies showed superior function. Further, determinant spreading was substantial in lymphoreplete hosts but absent in lymphopenic hosts. These results demonstrate that targeted therapies delivered to mimic the "physiology of lymphopenia" enhance the efficacy of adoptive immunotherapy in lymphoreplete hosts and provide a potentially superior alternative to the induction of lymphopenia.


Assuntos
Transferência Adotiva , Linfopenia/terapia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/transplante , Animais , Proliferação de Células/efeitos dos fármacos , Humanos , Subunidade alfa de Receptor de Interleucina-2/imunologia , Interleucina-7/imunologia , Interleucina-7/farmacologia , Linfopenia/imunologia , Linfopenia/fisiopatologia , Camundongos , Camundongos Knockout
16.
Int Immunopharmacol ; 95: 107586, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33765611

RESUMO

The incidence of the novel coronavirus disease (COVID-19) outbreak caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has brought daunting complications for people as well as physicians around the world. An ever-increasing number of studies investigating the characteristics of the disease, day by day, is shedding light on a new feature of the virus with the hope that eventually these efforts lead to the proper treatment. SARS-CoV-2 activates antiviral immune responses, but in addition may overproduce pro-inflammatory cytokines, causing uncontrolled inflammatory responses in patients with severe COVID-19. This condition may lead to lymphopenia and lymphocyte dysfunction, which in turn, predispose patients to further infections, septic shock, and severe multiple organ dysfunction. Therefore, accurate knowledge in this issue is important to guide clinical management of the disease and the development of new therapeutic strategies in patients with COVID-19. In this review, we provide a piece of valuable information about the alteration of each subtype of lymphocytes and important prognostic factors associated with these cells. Moreover, through discussing the lymphopenia pathophysiology and debating some of the most recent lymphocyte- or lymphopenia-related treatment strategies in COVID-19 patients, we tried to brightening the foreseeable future for COVID-19 patients, especially those with severe disease.


Assuntos
Tratamento Farmacológico da COVID-19 , COVID-19/imunologia , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/virologia , Linfopenia/imunologia , Linfopenia/fisiopatologia , SARS-CoV-2/imunologia , COVID-19/complicações , Humanos , Linfopenia/etiologia , Linfopenia/virologia , Prognóstico
17.
PLoS One ; 16(8): e0256205, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34388210

RESUMO

BACKGROUND: Lymphopenia is associated with various pathologies such as sepsis, burns, trauma, general anesthesia and major surgeries. All these pathologies are clinically expressed by the so-called Systemic Inflammatory Response Syndrome which does not include lymphopenia into defining criteria. The main objective of this work was to analyze the diagnosis of patients admitted to a hospital related to lymphopenia during hospital stay. In addition, we investigated the relationship of lymphopenia with the four levels of the Severity of Illness (SOI) and the Risk of Mortality (ROM). METHOD AND FINDINGS: Lymphopenia was defined as Absolute Lymphocyte Count (ALC) <1.0 x109/L. ALC were analyzed every day since admission. The four levels (minor, moderate, major and extreme risk) of both SOI and ROM were assessed. A total of 58,260 hospital admissions were analyzed. More than 41% of the patients had lymphopenia during hospital stay. The mean time to death was shorter among patients with lymphopenia on admission 65.6 days (CI95%, 57.3-73.8) vs 89.9 (CI95%, 82.4-97.4), P<0.001. Also, patients with lymphopenia during hospital stay had a shorter time to the mortality, 67.5 (CI95%, 61.1-73.9) vs 96.9 (CI95%, 92.6-101.2), P<0.001. CONCLUSIONS: Lymphopenia had a high prevalence in hospitalized patients with greater relevance in infectious pathologies. Lymphopenia was related and clearly predicts SOI and ROM at the time of admission, and should be considered as clinical diagnostic criteria to define SIRS.


Assuntos
Doenças Transmissíveis/mortalidade , Gastroenteropatias/mortalidade , Nefropatias/mortalidade , Pneumopatias/mortalidade , Linfopenia/mortalidade , Transtornos Mieloproliferativos/mortalidade , Sepse/mortalidade , Síndrome de Resposta Inflamatória Sistêmica/mortalidade , Idoso , Idoso de 80 Anos ou mais , Doenças Transmissíveis/diagnóstico , Doenças Transmissíveis/fisiopatologia , Feminino , Gastroenteropatias/diagnóstico , Gastroenteropatias/fisiopatologia , Mortalidade Hospitalar/tendências , Hospitais , Humanos , Nefropatias/diagnóstico , Nefropatias/fisiopatologia , Tempo de Internação/estatística & dados numéricos , Pneumopatias/diagnóstico , Pneumopatias/fisiopatologia , Contagem de Linfócitos , Linfopenia/diagnóstico , Linfopenia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/fisiopatologia , Estudos Retrospectivos , Sepse/diagnóstico , Sepse/fisiopatologia , Índice de Gravidade de Doença , Síndrome de Resposta Inflamatória Sistêmica/diagnóstico , Síndrome de Resposta Inflamatória Sistêmica/fisiopatologia
18.
Am J Infect Control ; 49(1): 82-89, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32540370

RESUMO

OBJECTIVE: We aimed to investigate the relationship between clinical characteristics, outcomes and the severity of severe acute respiratory syndrome coronavirus 2 pneumonia. METHODS: We performed a systematic review and meta-analysis using PubMed, Embase, and Cochrane Library databases to assess the clinical characteristics and outcomes of confirmed COVID-19 cases and compared severe (ICU) and nonsevere (non-ICU) groups. RESULTS: We included 12 cohort studies including 2,445 patients with COVID-19. Compared with nonsevere (non-ICU) patients, severe (ICU) disease was associated with a smoking history (P = .003) and comorbidities including chronic obstructive pulmonary disease (OR = 5.08, P < .001), diabetes (OR = 3.17, P < .001), hypertension (OR = 2.40, P < .001), coronary heart disease (OR = 2.66, P < .001), cerebrovascular diseases (OR = 2.68, P = .008), and malignancy (OR=2.21, P = .040). We found significant differences between the 2 groups for fever, dyspnea, decreased lymphocyte and platelet counts, and increased leukocyte count, C-creative protein, procalcitonin, lactose dehydrogenase, aspartate aminotransferase, alanine aminotransferase, creatinine kinase, and creatinine levels (P < .05). Significant differences were also observed for multiple treatments (P < .05). Patients in the severe (ICU) group were more likely to have complications and had a much higher mortality rate and lower discharge rate than those with nonsevere (non-ICU) disease (P < .05). CONCLUSIONS: Investigation of clinical characteristics and outcomes of severe cases of COVID-19 will contribute to early prediction, accurate diagnosis, and treatment to improve the prognosis of patients with severe illness.


Assuntos
COVID-19/fisiopatologia , Dispneia/fisiopatologia , Febre/fisiopatologia , Leucocitose/fisiopatologia , Linfopenia/fisiopatologia , Trombocitopenia/fisiopatologia , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Proteína C-Reativa/metabolismo , COVID-19/sangue , COVID-19/mortalidade , Transtornos Cerebrovasculares/epidemiologia , Comorbidade , Doença das Coronárias/epidemiologia , Creatina Quinase/sangue , Creatinina/sangue , Diabetes Mellitus/epidemiologia , Humanos , Hipertensão/epidemiologia , Unidades de Terapia Intensiva , L-Lactato Desidrogenase/sangue , Leucocitose/sangue , Linfopenia/sangue , Pró-Calcitonina/sangue , Doença Pulmonar Obstrutiva Crônica/epidemiologia , SARS-CoV-2 , Índice de Gravidade de Doença , Fumar/epidemiologia , Trombocitopenia/sangue
19.
Chest ; 159(2): e107-e113, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33563452

RESUMO

CASE PRESENTATION: A 53-year-old man presented to the ED at a time of low severe acute respiratory syndrome coronavirus 2, also known as coronavirus disease 2019 (COVID-19), prevalence and reported 2 weeks of progressive shortness of breath, dry cough, headache, myalgias, diarrhea, and recurrent low-grade fevers to 39°C for 1 week with several days of recorded peripheral capillary oxygen saturation of 80% to 90% (room air) on home pulse oximeter. Five days earlier, he had visited an urgent care center where a routine respiratory viral panel was reportedly negative. A COVID-19 reverse transcriptase polymerase chain reaction test result was pending at the time of ED visit. He reported a past medical history of gastroesophageal reflux disease that was treated with famotidine. Travel history included an out-of-state trip 3 weeks earlier, but no recent international travel.


Assuntos
COVID-19/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Bacteriemia/complicações , COVID-19/complicações , COVID-19/fisiopatologia , Teste de Ácido Nucleico para COVID-19 , Doenças Cerebelares/complicações , Doenças Cerebelares/diagnóstico por imagem , Tosse/fisiopatologia , Diarreia/fisiopatologia , Progressão da Doença , Dispneia/fisiopatologia , Serviço Hospitalar de Emergência , Febre/fisiopatologia , Cefaleia/fisiopatologia , Humanos , AVC Isquêmico/complicações , AVC Isquêmico/diagnóstico por imagem , Linfopenia/fisiopatologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mialgia/fisiopatologia , Oximetria , Pneumonia Estafilocócica/complicações , Radiografia Torácica , SARS-CoV-2 , Infecções Estafilocócicas/complicações , Tomografia Computadorizada por Raios X
20.
Hum Antibodies ; 29(1): 49-54, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32986663

RESUMO

Coronavirus disease 2019 (COVID-19) has caused a global pandemic in early 2020. This infectious disorder has a heterogeneous course ranging from asymptomatic disorder to a critical situation needing intensive cares. In the current study, we present a report of affected patients admitted in a single hospital in Iran. Eighty-two hospitalized patients with COVID-19 were assessed. Demographic, clinical, and paraclinical parameters were gathered and statistically analyzed. The median age (IQR) of the patients was 57.32 (45.75, 70) years. At primary evaluation, fever was present in 45.12% of the affected individuals. The most common clinical symptoms were dyspnea (81.71%) and cough (65.85%). Totally, 12 (14.63%) and 14 (17.07%) of patients had low and high WBC counts, respectively. Lymphopenia was detected in 36 (43.9%) of patients, while 6 (7.32%) of patients had lymphocytosis. High levels of Il-6 were detected in 4 (4.88%) of patients. CRP levels were elevated in 69 (84.1%) of patients. The median (IQR) of hospitalization was 7 (5, 9) days. Totally, 26 patients (31%) were hospitalized in ICU. All patients were discharged with good health conditions except for one patient who died. The current study shows the heterogeneous clinical manifestations and paraclinical parameters of COVID-19 patients.


Assuntos
COVID-19/fisiopatologia , Tosse/fisiopatologia , Dispneia/fisiopatologia , Febre/fisiopatologia , Linfocitose/fisiopatologia , Linfopenia/fisiopatologia , Idoso , Proteína C-Reativa/metabolismo , COVID-19/mortalidade , COVID-19/terapia , COVID-19/virologia , Tosse/mortalidade , Tosse/terapia , Tosse/virologia , Diabetes Mellitus/mortalidade , Diabetes Mellitus/fisiopatologia , Diabetes Mellitus/terapia , Diabetes Mellitus/virologia , Dispneia/mortalidade , Dispneia/terapia , Dispneia/virologia , Feminino , Febre/mortalidade , Febre/terapia , Febre/virologia , Hospitais , Humanos , Hipertensão/mortalidade , Hipertensão/fisiopatologia , Hipertensão/terapia , Hipertensão/virologia , Irã (Geográfico) , Contagem de Leucócitos , Linfocitose/mortalidade , Linfocitose/terapia , Linfocitose/virologia , Linfopenia/mortalidade , Linfopenia/terapia , Linfopenia/virologia , Masculino , Pessoa de Meia-Idade , Obesidade/mortalidade , Obesidade/fisiopatologia , Obesidade/terapia , Obesidade/virologia , Oxigênio/uso terapêutico , Respiração Artificial/métodos , Estudos Retrospectivos , SARS-CoV-2/patogenicidade , Índice de Gravidade de Doença , Análise de Sobrevida
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