RESUMO
An association between varicella zoster virus (VZV) and multiple sclerosis (MS) has been reported in Mexican populations. The aim of this study was to compare the response of T cells from MS patients, during relapse and remission, to in vitro stimulation with VZV, adenovirus (AV) and Epstein-Barr virus (EBV). Proliferation and cytokine secretion of T cells from 29 relapsing-remitting MS patients and 38 healthy controls (HC) were analyzed by flow cytometry after stimulating with VZV, AV or EBV. IgG and IgM levels against VZV and EBV were quantified using Enzyme-Linked Immunosorbent Assay. Relapsing MS patients showed a higher percentage of responding CD4+ and CD8+ T cells against VZV compared to AV. In HC and remitting MS patients, proliferation of CD4+ T cells was higher when stimulated with VZV as compared to EBV. Moreover, T cells isolated from remitting patients secreted predominantly Th1 cytokines when cell cultures were stimulated with VZV. Finally, high concentration of anti-VZV IgG was found in sera from patients and controls. The results support previous studies of an VZV-MS association in the particular population studied and provide additional information about the possible role of this virus in the pathogenesis of MS.
Assuntos
Herpesvirus Humano 3/fisiologia , Esclerose Múltipla/imunologia , Esclerose Múltipla/virologia , Linfócitos T/imunologia , Adenoviridae/fisiologia , Adulto , Anticorpos Antivirais/imunologia , Citocinas/metabolismo , Feminino , Herpesvirus Humano 3/imunologia , Herpesvirus Humano 4/imunologia , Herpesvirus Humano 4/fisiologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Esclerose Múltipla Recidivante-Remitente/imunologia , Esclerose Múltipla Recidivante-Remitente/virologia , Recidiva , Indução de RemissãoRESUMO
Bell's Palsy is the most frequent acute neuropathy of cranial nerves; it has been associated in various reports to herpes viruses. In a prospective study we searched the presence of DNA from five herpes viruses (HSV-1 and 2, VZV, EBV and HHV-6) in 79 patients at the acute phase of Bell's Palsy. Results were related with various parameters; age, gender and clinical outcome. We found the significant presence (pË0.001) of HSV-1 and VZV in 39% and 42% of patients. However, a large percentage of cases were negative. When comparisons were made between subgroups according to gender and age no differences were found with viral findings nor with clinical outcome of palsy, which was of clinical remission in most cases (78%). Our results suggest that herpes viruses might participate in the complex mechanisms of autoimmunity of Bell's Palsy but not as determinant etiological element.
Assuntos
Corticosteroides/uso terapêutico , Antivirais/uso terapêutico , Paralisia de Bell/tratamento farmacológico , Herpesvirus Humano 1/genética , Herpesvirus Humano 3/genética , Aciclovir/uso terapêutico , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/sangue , Autoimunidade , Paralisia de Bell/imunologia , Paralisia de Bell/patologia , Paralisia de Bell/virologia , Estudos de Casos e Controles , DNA Viral/sangue , DNA Viral/genética , Nervo Facial/efeitos dos fármacos , Nervo Facial/imunologia , Nervo Facial/patologia , Nervo Facial/virologia , Feminino , Herpesvirus Humano 1/patogenicidade , Herpesvirus Humano 2/genética , Herpesvirus Humano 3/patogenicidade , Herpesvirus Humano 4/genética , Herpesvirus Humano 6/genética , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Indução de Remissão , Fatores Sexuais , Resultado do TratamentoRESUMO
OBJECTIVE: Optic Neuritis (ON) might unfold either as a single intracranial neuritis or as multiple sclerosis, a widespread demyelinating disorder. Different herpes viruses have been proposed as potential participants in the etiology of multiple sclerosis (MS). To analyze the potential presence of herpes viruses in blood and subarachnoid area at the time of ON and contrast the findings according to long-term evolution either as intracranial neuritis or as progression to multiple sclerosis. PATIENTS AND METHODS: In a prospective investigation we searched the presence of DNA from 5 herpes viruses (HSV-1, HSV-2, VZV, EBV and HHV6) in CSF and blood lymphocytes from 54 patients with ON, patients were followed 62⯱â¯3 months; those who developed MS were separated from those with ephemeral ON. Long-term prognosis of ON was related to DNA findings. RESULTS: As compared with controls, DNA from HSV-1 was significantly more frequent in CSF and blood from cases with ON; VZV and HSV-2 were found only in CSF; EBV was found only in blood samples (pâ¯<â¯0.006). CONCLUSIONS: Our results point out the potential participation of HSV, VZV and EBV in ON; suggesting the intervention of various herpes viruses as triggering agents of autoimmunity. However, the number of positive cases was minor than negative cases. Also, our results suggest that the etiological mechanisms in ON could be similar to those of neuritis of the facial nerve (Bell's palsy).
Assuntos
DNA Viral/líquido cefalorraquidiano , Infecções por Herpesviridae/epidemiologia , Herpesviridae/genética , Neurite Óptica/virologia , Adulto , Paralisia de Bell/virologia , DNA Viral/sangue , Infecções por Vírus Epstein-Barr/epidemiologia , Feminino , Herpes Simples/epidemiologia , Herpesvirus Humano 1/genética , Herpesvirus Humano 2/genética , Herpesvirus Humano 3/genética , Herpesvirus Humano 4/genética , Herpesvirus Humano 6/genética , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/fisiopatologia , Neurite Óptica/epidemiologia , Neurite Óptica/metabolismo , Neurite Óptica/fisiopatologia , Prognóstico , Infecções por Roseolovirus/epidemiologia , Infecção pelo Vírus da Varicela-Zoster/epidemiologia , Adulto JovemRESUMO
Viral agents have been suspected as participants of immune-mediated disorders. In the case of rheumatic diseases, the synovial joint cavity represents a secluded area of inflammation which could harbor etiological agents. We analyzed by polymerase chain reaction the possible presence of DNA from various herpes viruses in blood and synovial fluid from patients with either rheumatoid arthritis (n = 18), axial spondyloarthritis (n = 11), or osteoarthritis (n = 8). Relevant findings were as follows: DNA from varicella zoster virus was found in synovial fluid but not in blood mononuclear cells from 33 % of patients with rheumatoid arthritis and in 45 % of patients with axial spondyloarthritis but not in patients with osteoarthritis. Also, DNA from herpes simplex viruses 1 and 2 was found both in the blood and in the synovial fluid from 33 % of patients with rheumatoid arthritis. Our results indicate the occasional presence of DNA from herpes viruses in patients with rheumatoid arthritis or with axial spondyloarthritis. However, these findings might represent a parallel epiphenomenon of viral activation associated either with immunosuppressive therapy or with primary immune disturbances, rather than the etiological participation of herpes viruses in these disorders.
Assuntos
Artrite Reumatoide/sangue , Artrite Reumatoide/virologia , Herpesviridae , Espondilartrite/sangue , Espondilartrite/virologia , Líquido Sinovial/virologia , Adulto , Idoso , Anticorpos Antivirais/análise , Estudos Transversais , DNA Viral/análise , Feminino , Herpesvirus Humano 1 , Herpesvirus Humano 2 , Herpesvirus Humano 3 , Herpesvirus Humano 4 , Herpesvirus Humano 6 , Humanos , Imunoglobulina G/análise , Imunoglobulina M/análise , Leucócitos Mononucleares/virologia , Masculino , Pessoa de Meia-Idade , Osteoartrite/virologia , Reação em Cadeia da Polimerase em Tempo Real , Adulto JovemRESUMO
BACKGROUND: Few studies, have evaluated the prognostic impact of the quantification of mRNA expression levels in advanced non-small cell lung cancer (NSCLC). OBJECTIVE: The aim of this work was to quantify mRNA expression levels in peripheral blood through three epithelial markers in patients with stages IIIB and IV in NSCLC. METHODS: Seventy advanced NSCLC patients and ten healthy controls were included. All patients received platinum-based chemotherapy in first line treatment. Peripheral blood was obtained of each participant and mRNA expression levels present in circulating cells were quantified by molecular techniques (RT-PCR) using three epithelial markers: cytokeratin (CK)-18, CK-19 and Carcinoembryonic-Antigen (CEA). The expression levels were quantified from a standard curve using the cDNA obtained from A549 cells. Registered in ClinicalTrials.gov (NCT01052818). RESULTS: We found a significant statistical correlation between levels of CK-18, CK-19 and CEA mRNA. mRNA expression levels were lower in patients who present three or less metastasis; higher CEA mRNA expression was associated a worse progression-free survival to platinum-based chemotherapy and overall survival. CONCLUSION: RNA expression of CEA by RT-PCR is useful as a prognostic marker in advanced NSCLC.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/genética , Células Neoplásicas Circulantes/metabolismo , Células Neoplásicas Circulantes/patologia , RNA Mensageiro/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro/genética , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: Recent studies have documented the apparent participation of varicella zoster virus (VZV) in the etiopathogenesis of multiple sclerosis (MS). The present study aimed to corroborate the possible presence of VZV during exacerbations of MS. DESIGN: Fifty-three patients with definite MS were included; of them, 31 were studied during the first week of a clinical relapse, whereas 16 were studied during remission; 6 patients with progressive MS were also studied. Genes from 5 herpes viruses: varicella zoster, herpes simplex 1 and 2, Epstein-Barr and herpes 6 were studied by polymerase chain reaction in cerebrospinal fluid and in peripheral blood mononuclear cells (PBMC). As controls 21 patients with inflammatory or functional neurological disorders were included. RESULTS: DNA from varicella zoster virus was found in the CSF from all MS patients studied during relapse (100%) and in the PBMC from 28 of them (90%). However, VZV DNA was found in the CSF only in 5 MS patients studied during remission (31%) and in the PBMC from 3 of them (19%). VZV DNA was also found, but in lower amounts, in the CSF (83%) and PBMC (33%) from patients with progressive MS. In contrast, VZV was not found either in CSF or in PBMC from controls. Results from the other herpes viruses tested were similar in MS patients and in controls. CONCLUSIONS: Our results corroborate the conspicuous, but ephemeral presence of VZV during relapses of MS and support the idea of VZV involvement in the etiopathogenesis of MS. Recent epidemiological and molecular studies as well as reports of severe VZV infections triggered by specifically induced immunosuppression during therapy of MS give additional support to this potential association.
Assuntos
DNA Viral/líquido cefalorraquidiano , Herpesvirus Humano 3/genética , Leucócitos Mononucleares/virologia , Esclerose Múltipla Crônica Progressiva/virologia , Esclerose Múltipla Recidivante-Remitente/virologia , Estudos de Casos e Controles , DNA Viral/sangue , Progressão da Doença , Herpesvirus Humano 1/genética , Herpesvirus Humano 2/genética , Herpesvirus Humano 4/genética , Herpesvirus Humano 6/genética , Humanos , Esclerose Múltipla Crônica Progressiva/sangue , Esclerose Múltipla Crônica Progressiva/líquido cefalorraquidiano , Esclerose Múltipla Recidivante-Remitente/sangue , Esclerose Múltipla Recidivante-Remitente/líquido cefalorraquidiano , Reação em Cadeia da Polimerase em Tempo Real , RecidivaRESUMO
BACKGROUND: A possible viral cause for multiple sclerosis (MS) has long been suspected. A progressive increase in MS has been reported in Mexico during the past 20 years; a conspicuous antecedent of varicella infection during childhood has been the most relevant finding in the medical history of patients with MS. OBJECTIVE: To investigate the possible participation of varicella-zoster virus (VZV) in the etiopathogenesis of MS. DESIGN, SETTING, AND PATIENTS: We searched, by polymerase chain reaction (PCR), for VZV DNA in peripheral mononuclear cells of 82 patients with relapsing-remitting MS. Additionally, genes gD from herpes simplex viruses 1 and 2 were sought by PCR, as well as IgG and IgM serum antibodies to VZV. RESULTS: Viral DNA from the genes open reading frame (ORF)31, ORF62, ORF63, and ORF67 of VZV was found in mononuclear cells from 13 (87%) of 15 patients with MS who were tested during acute relapse. All patients who were tested during remission (n = 67) were negative for the DNA, including patients who were initially positive and were tested again after 2 months of remission. All control patients with a comprehensive variety of neurologic diseases (n = 100) and healthy controls (n = 20) also tested negative. All subjects were negative for herpes simplex viruses 1 and 2 DNA, and no differences were found in serum antibodies to VZV. CONCLUSIONS: The finding of genes of VZV in peripheral mononuclear cells, restricted to a brief period during clinical relapse of MS, suggests either its participation in the etiopathogenesis of MS or an epiphenomenon of viral activation simultaneous with the relapse of MS.
Assuntos
DNA Viral/sangue , Herpesvirus Humano 3/genética , Leucócitos Mononucleares/virologia , Esclerose Múltipla Recidivante-Remitente/virologia , Adolescente , Adulto , Anticorpos Antivirais/sangue , Varicela/imunologia , Varicela/virologia , Feminino , Herpesvirus Humano 1/genética , Herpesvirus Humano 1/imunologia , Herpesvirus Humano 2/genética , Herpesvirus Humano 2/imunologia , Herpesvirus Humano 3/imunologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Leucócitos Mononucleares/imunologia , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/imunologia , Reação em Cadeia da Polimerase , Fatores de Risco , Proteínas do Envelope Viral/sangue , Proteínas do Envelope Viral/genéticaRESUMO
An association between brain cysticercosis and malignant neoplasms in humans has recently been reported. To explore the possibility of a potentiating effect of cysticercosis on carcinogenesis mice infected with Taenia crassiceps cysticerci were exposed to the carcinogenic substance methyl-nitrosourea; 35% of them developed lymphoma, in contrast with 50% of control non-infected animals exposed to MNU. In this experimental model of cysticercosis we did not find a potentiating effect of peritoneal cysticercosis on the carcinogenicity of MNU.