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1.
Cells ; 9(1)2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31936602

RESUMO

A point mutation (P56S) in the gene-encoding vesicle-associated membrane-protein-associated protein B (VAPB) leads to an autosomal-dominant form of amyotrophic lateral sclerosis (ALS), classified as ALS-8. The mutant VAPB is characterized by ER-associated aggregates that lead to a complete reorganization of ER structures. Growing evidences suggest VAPB involvement in ALS pathomechanisms. In fact, numerous studies demonstrated VAPB alteration also in sporadic ALS (sALS) and showed the presence of its aggregates when others ALS-related gene are mutant. Recently, the identification of new biomarkers in peripheral blood mononuclear cells (PBMCs) has been proposed as a good noninvasive option for studying ALS. Here, we evaluated VAPB as a possible ALS pathologic marker analyzing PBMCs of sALS patients. Immunofluorescence analysis (IFA) showed a peculiar pattern of VAPB aggregates in sALS, not evident in healthy control (HC) subjects and in Parkinson's disease (PD) PBMCs. This specific pattern led us to suppose that VAPB could be misfolded in sALS. The data indirectly confirmed by flow cytometry assay (FCA) showed a reduction of VAPB fluorescent signals in sALS. However, our observations were not associated with the presence of a genetic mutation or altered gene expression of VAPB. Our study brings further evidences of the VAPB role in ALS as a diagnostic biomarker.

2.
J Neuroimmunol ; 338: 577110, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31715457

RESUMO

Increased expression of the retroviruses of HERV-W family has been linked to multiple sclerosis (MS) pathophysiology; nothing is known at the moment about MOG-IgG associated disorders. We compared antibody response against HERV-W peptides among patients with MOG-IgG associated disorders, multiple sclerosis (MS) and aquaporin-4 (AQP4)-IgG positive neuromyelitis optica spectrum disorder (NMOSD). A total of 102 serum samples were retrospectively analyzed. Antibody reactivity against HERV-W env peptides was similar in MOG-IgG associated disorders and MS, but different from AQP4-IgG positive NMOSD. Our findings expand the diagnostic role of HERV-W antibodies to the spectrum of demyelinating disorders associated with MOG-IgG.

3.
J Circ Biomark ; 8: 1849454419875912, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31588250

RESUMO

Myasthenia gravis (MG) is an autoimmune disease leading to varying degrees of skeletal muscle weakness. It is caused by specific antibodies directed against definite components in the postsynaptic membrane at the neuromuscular junction (NMJ), such as the acetylcholine receptor (AChR) and the muscle-specific kinase (MUSK) receptor. In clinical practice, MG patients may be classified into three main subgroups based on the occurrence of serum autoantibodies directed against AChR or MUSK receptor or antibody-negative. As the MG subgroups differ in terms of clinical characteristics, disease pathogenesis, prognosis, and response to therapies, they could benefit from targeted treatment as well as the detection of other possible disease biomarkers. We performed proteomics on plasma fractions enriched in low-abundance proteins to identify potential biomarkers according to different autoimmune responses. By this approach, we evidenced a significant reduction of vitronectin in MG patients compared to healthy controls, irrespective of the autoantibodies NMJ target. The obtained results were validated by mono- and two-dimensional Western blotting analysis. Vitronectin is a multifunctional glycoprotein involved in the regulation of several pathophysiological processes, including complement-dependent immune response, coagulation, fibrinolysis, pericellular proteolysis, cell attachment, and spreading. The pathophysiological significance of the reduction of plasma vitronectin in MG patients has yet to be fully elucidated. It could be related either to a possible deposition of vitronectin at NMJ to counteract the complement-mediated muscle damage at this level or to a parallel variation of this glycoprotein in the muscle extracellular matrix with secondary induced alteration in clustering of AChRs at NMJ, as it occurs with variation in concentrations of agrin, another extracellular matrix component. The clinical value of measuring plasma vitronectin has yet to be defined. According to present findings, significantly lower plasma values of this glycoprotein might be indicative of an impaired complement-dependent immune response.

4.
Microorganisms ; 7(10)2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31597322

RESUMO

Environmental factors such as bacterial infections may play an important role in the development of autoimmune diseases. Mycobacterium avium subsp. paratuberculosis (MAP) is an obligate pathogen of ruminants able to use the host's cholesterol for survival into macrophages and has been associated with multiple sclerosis (MS), type 1 diabetes (T1DM) and rheumatoid arthritis (RA) through a molecular mimicry mechanism. Here, we aimed at investigating the correlation between humoral reactivity against MAP and serum lipoprotein levels in subjects at T1DM risk (rT1DM) grouped by geographical background and in patients affected by MS or RA. Our results showed significant differences in HDL, LDL/VLDL and Total Cholesterol (TC) levels between patients and healthy controls (p < 0.0001). Patients positive to anti-MAP Abs (MAP+) had lower HDL levels in comparison with Abs negative (MAP-) subjects, while opposite trends were found for LDL/VLDL concentrations (p < 0.05). TC levels varied between MAP+ and MAP- patients in all three assessed diseases. These findings suggest the implication of anti-MAP Abs in fluctuations of lipoprotein levels highlighting a possible link with cardiovascular disease. Further studies will be needed to confirm these results in larger groups.

5.
Front Neurol ; 10: 122, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30837941

RESUMO

Parkinson's disease is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons of the substantia nigra pars compacta with a reduction of dopamine concentration in the striatum. The complex interaction between genetic and environmental factors seems to play a role in determining susceptibility to PD and may explain the heterogeneity observed in clinical presentations. The exact etiology is not yet clear, but different possible causes have been identified. Inflammation has been increasingly studied as part of the pathophysiology of neurodegenerative diseases, corroborating the hypothesis that the immune system may be the nexus between environmental and genetic factors, and the abnormal immune function can lead to disease. In this review we report the different aspects of inflammation and immune system in Parkinson's disease, with particular interest in the possible role played by immune dysfunctions in PD, with focus on autoimmunity and processes involving infectious agents as a trigger and alpha-synuclein protein (α-syn).

6.
eNeurologicalSci ; 13: 1-4, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30255159

RESUMO

Parkinson's disease is a neurodegenerative disorder and its etiology is unknown, numerous studies show how different environmental factors can influence the development of disease. miRNAs are involved in several pathologies and their dysregulation contribute to different pathologies, also in neurodegenerative such as Parkinson's disease, Alzheimer's disease, Huntington's disease and Amyotrophic lateral sclerosis. In this study, we profiled the expression of different candidate miRNAs: miR-155, miR-26a, miR-146a, and miR132, in PBMCs of L-dopa treated Parkinson patients and unaffected controls (HCs).We investigated the expression of miRNAs by RT-real time PCR, the results were subjected to statistical analysis. miRNA-155-5p was generally up-regulated in PD patients compared to HCs whereas miRNA-146a-5p was down-regulated in PD patients in comparison to HCs. It is interesting to point out that the expression of miR-155-5p was modified by levodopa treatment, in fact a down-regulation of miR-155-5p in PD patients with the highest dosage was observed. In conclusion, miRNA 155 could not only be a promising target for the anti-inflammatory therapy in PD but also a good candidate as a disease progression biomarker. The role of levodopa in modulating the levels of miRNA 155 requires further studies.

7.
J Neuroimmunol ; 323: 49-52, 2018 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-30196833

RESUMO

Mycobacterium avium ssp. paratuberculosis (Map) is the etiological agent of Paratuberculosis in ruminants. Protein tyrosine phosphatase A (PtpA) and protein kinase G (PknG) are secreted proteins necessary for the survival of the pathogen within macrophages. In this study we analyzed if Map was able to grow within astrocytes and investigated on the presence of antibodies against PtpA and PknG proteins in MS and NMOSD patients by ELISA. Map was unable to proliferate in astrocytes after of 72 h post-infection, but we observed a high level of antibodies against both virulence factors, suggesting that these patients have been exposed/infected with Map.


Assuntos
Anticorpos Antibacterianos/sangue , Proteínas de Bactérias/sangue , Esclerose Múltipla/sangue , Mycobacterium avium subsp. paratuberculosis/metabolismo , Neuromielite Óptica/sangue , Proteínas Tirosina Fosfatases/sangue , Proteínas Serina-Treonina Quinases/sangue , Adulto , Astrócitos/metabolismo , Astrócitos/microbiologia , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/microbiologia , Neuromielite Óptica/microbiologia
8.
J Neuroimmunol ; 318: 97-102, 2018 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-29519720

RESUMO

Epstein-Barr virus (EBV) is the main environmental agent associated to neuromyelitis optica spectrum disorder (NMOSD). Following to studies reporting an increased prevalence of antibodies against peptides derived from Mycobacterium avium subsp. paratuberculosis (MAP) homologous to EBV and human epitopes (MBP85-98, IRF5424-434) in multiple sclerosis (MS), we investigated whether seroreactivity to these antigens display a NMOSD-specific pattern. The sera of 34 NMOSD patients showed elevated levels of antibodies against MAP and MBP compared to healthy controls (44% vs. 5%, p < 0.0002 and 50% vs. 2%, p < 0.0001, respectively), while, unlike in MS, responsiveness to EBV was similar.


Assuntos
Anticorpos Antibacterianos/imunologia , Autoanticorpos/imunologia , Mycobacterium avium subsp. paratuberculosis/imunologia , Proteína Básica da Mielina/imunologia , Neuromielite Óptica/imunologia , Adulto , Antígenos de Bactérias/imunologia , Autoantígenos/imunologia , Epitopos/imunologia , Feminino , Humanos , Fatores Reguladores de Interferon/imunologia , Masculino , Pessoa de Meia-Idade
9.
Mult Scler J Exp Transl Clin ; 3(4): 2055217317742425, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29204291

RESUMO

Background: A specific humoral immune response against HERV-W envelope surface (env-su) glycoprotein antigens has been reported in serum of patients with multiple sclerosis (MS). However, it has not been evaluated to date in patients with neuromyelitis optica spectrum disorder (NMOSD). Objective: The objective of this paper is to investigate whether antibody (Ab) response against HERV-W env-su antigenic peptides differs between NMOSD and MS. Methods: Serum samples were collected from 36 patients with NMOSD, 36 patients with MS and 36 healthy control individuals (HCs). An indirect ELISA was set up to detect specific Abs against HERV-W env-su peptides. Results: Our data showed that two antigenic peptides, particularly HERV-Wenv93-108 and HERV-Wenv248-262, were statistically significantly present only in serum of MS compared to NMOSD and HCs. Thus, the specific humoral immune response against HERV-W env-su glycoprotein antigens found in MS is widely missing in NMOSD. Conclusion: Increased circulating serum levels of these HERV-W Abs may be suitable as additional biomarkers to better differentiate MS from NMOSD.

10.
J Neurovirol ; 23(2): 226-238, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27812788

RESUMO

Natalizumab is effective against multiple sclerosis (MS), but is associated with progressive multifocal leukoencephalopathy (PML), fatal disease caused by the JCV polyomavirus. The SF2/ASF (splicing factor2/alternative splicing factor) inhibits JCV in glial cells. We wondered about SF2/ASF modulation in the blood of natalizumab-treated patients and if this could influence JCV reactivation. Therefore, we performed a longitudinal study of MS patients under natalizumab, in comparison to patients under fingolimod and to healthy blood donors. Blood samples were collected at time intervals. The expression of SF2/ASF and the presence and expression of JCV in PBMC were analyzed. A bell-shaped regulation of SF2/ASF was observed in patients treated with natalizumab, increased in the first year of therapy, and reduced in the second one, while slightly changed, if any, in patients under fingolimod. Notably, SF2/ASF was up-regulated, during the first year, only in JCV DNA-positive patients, or with high anti-JCV antibody response; the expression of the JCV T-Ag protein in circulating B cells was inversely related to SF2/ASF protein expression. The SF2/ASF reduction, parallel to JCV activation, during the second year of therapy with natalizumab, but not with fingolimod, may help explain the increased risk of PML after the second year of treatment with natalizumab, but not with fingolimod. We propose that SF2/ASF has a protective role against JCV reactivation in MS patients. This study suggests new markers of disease behavior and, possibly, help in re-evaluations of therapy protocols.


Assuntos
Interações Hospedeiro-Patógeno , Fatores Imunológicos/uso terapêutico , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Natalizumab/uso terapêutico , Fatores de Processamento de Serina-Arginina/genética , Adulto , Anticorpos Antivirais/sangue , Relação Dose-Resposta a Droga , Feminino , Cloridrato de Fingolimode/uso terapêutico , Regulação da Expressão Gênica , Humanos , Vírus JC/efeitos dos fármacos , Vírus JC/genética , Vírus JC/crescimento & desenvolvimento , Leucoencefalopatia Multifocal Progressiva/imunologia , Leucoencefalopatia Multifocal Progressiva/virologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla Recidivante-Remitente/imunologia , Esclerose Múltipla Recidivante-Remitente/virologia , Neuroglia/efeitos dos fármacos , Neuroglia/imunologia , Neuroglia/virologia , Fatores de Processamento de Serina-Arginina/imunologia , Transdução de Sinais , Ativação Viral/efeitos dos fármacos
11.
Sci Rep ; 6: 29268, 2016 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-27383531

RESUMO

Elevated B lymphocyte activating factor BAFF levels have been reported in multiple sclerosis (MS) patients; moreover, disease-modifying treatments (DMT) have shown to influence blood BAFF levels in MS patients, although the significance of these changes is still controversial. In addition, BAFF levels were reported increased during infectious diseases. In our study, we wanted to investigate on the serum BAFF concentrations correlated to the antibody response against Mycobacterium avium subspecies paratuberculosis (MAP), Epstein-Barr virus (EBV) and their human homologous epitopes in MS and in patients affected with other neurological diseases (OND), divided in Inflammatory Neurological Diseases (IND), Non Inflammatory Neurological Diseases (NIND) and Undetermined Neurological Diseases (UND), in comparison to healthy controls (HCs). Our results confirmed a statistically significant high BAFF levels in MS and IND patients in comparison to HCs but not NIND and UND patients. Interestingly, BAFF levels were inversely proportional to antibodies level against EBV and MAP peptides and the BAFF levels significantly decreased in MS patients after methylprednisolone therapy. These results implicate that lower circulating BAFF concentrations were present in MS patients with humoral response against MAP and EBV. In conclusion MS patients with no IgGs against EBV and MAP may support the hypothesis that elevated blood BAFF levels could be associated with a more stable disease.


Assuntos
Anti-Inflamatórios/uso terapêutico , Fator Ativador de Células B/sangue , Infecções por Vírus Epstein-Barr/sangue , Esclerose Múltipla/tratamento farmacológico , Paratuberculose/sangue , Prednisolona/uso terapêutico , Soro/metabolismo , Adulto , Idoso , Anticorpos Antibacterianos/metabolismo , Epitopos/uso terapêutico , Infecções por Vírus Epstein-Barr/tratamento farmacológico , Infecções por Vírus Epstein-Barr/virologia , Feminino , Herpesvirus Humano 4/efeitos dos fármacos , Humanos , Imunoglobulina G/metabolismo , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/microbiologia , Esclerose Múltipla/virologia , Mycobacterium avium subsp. paratuberculosis/efeitos dos fármacos , Doenças do Sistema Nervoso/sangue , Doenças do Sistema Nervoso/tratamento farmacológico , Doenças do Sistema Nervoso/microbiologia , Paratuberculose/microbiologia , Peptídeos/metabolismo
12.
J Mol Neurosci ; 60(1): 91-3, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27370541

RESUMO

B cells are being recognized as one of the major players in the pathogenesis of multiple sclerosis (MS). The B cell activating factor (BAFF) system plays an essential role in B cell homeostasis and function in the periphery. Mycobacterium avium subspecies paratuberculosis (MAP) has been previously associated to MS in Sardinia. Antibodies against a MAP surface protein, MAP_2694, have been found significantly associated to MS patients, and this response was modified by interferon-ß therapy. Increased BAFF levels following IFN-ß therapy have been also described in MS patients. In this study, we evaluated whether soluble BAFF levels are comparable in men and women affected by MS and performed a correlation of the reported BAFF increase in MS patients under IFN-ß therapy with changes of humoral response against MAP_2694. For these reasons, we investigated 44 MS patients before and after IFN-ß therapy. A significant difference of BAFF levels was found between men and women with MS; moreover, we confirmed that IFN-ß therapy strongly induces BAFF serum levels, but this was not related to the modification of immunological response against MAP_2694. In conclusion, our study highlights that IFN-ß therapy induces the potent B cell survival factor BAFF without alterations of the humoral immune response against MAP.


Assuntos
Fator Ativador de Células B/sangue , Fatores Imunológicos/uso terapêutico , Interferon beta/uso terapêutico , Esclerose Múltipla/sangue , Mycobacterium avium/imunologia , Paratuberculose/sangue , Adulto , Anticorpos Antibacterianos/sangue , Estudos de Casos e Controles , Feminino , Humanos , Fatores Imunológicos/efeitos adversos , Interferon beta/efeitos adversos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/complicações , Esclerose Múltipla/tratamento farmacológico , Paratuberculose/complicações
13.
PLoS One ; 11(6): e0157153, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27310932

RESUMO

MicroRNAs fine-tune the regulation of Th1/Th17 lymphocyte subsets in multiple sclerosis. We investigated the expression of miRNAs (previously associated with mycobacterial and viral infections) in MS patients and healthy donors (HD) following 6 months natalizumab therapy. In addition, Th1/Th17 cytokines and the presence of anti-EBNA1/VCA IgG in MS patients with different pattern of miRNA expression have been evaluated. MiR-155, miR-26a, miR-132, miR-146a and Th1/Th17 cytokines expression was detected by RT-real time PCR; moreover anti-EBNA1 and VCA IgG titres were measured by ELISA. We observed an up-regulation of miR-155 (p value = 0.009) and miR-132 (p value = 0.04) in MS patients compared to HD. In MS patients, IL-17a (p = 0.037), IFN γ (p = 0.012) and TNFα (p = 0.015) but not IL-6 were over-expressed compared to HD. Two different miRNAs patterns associated to the expression of different cytokines were observed in the MS cohort. Moreover, a down-regulation of miR-155 and miR-26a was seen in MS patients during and after natalizumab therapy. MS patients that over-expressed miR-155 showed a higher EBNA1 IgG titer than MS patients with high levels of miR-26a. In conclusions the expression of particular miRNAs modulates the pro-inflammatory cytokine expression and the humoral response against EBV and this expression is natalizumab regulated.


Assuntos
MicroRNAs/biossíntese , Esclerose Múltipla/tratamento farmacológico , Natalizumab/administração & dosagem , Adulto , Citocinas/imunologia , Antígenos Nucleares do Vírus Epstein-Barr/biossíntese , Antígenos Nucleares do Vírus Epstein-Barr/genética , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Imunoglobulina G/imunologia , Imunoglobulina G/isolamento & purificação , Interleucina-17/biossíntese , Interleucina-6/biossíntese , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Fator de Necrose Tumoral alfa/biossíntese
14.
J Neuroimmunol ; 293: 86-90, 2016 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-27049567

RESUMO

In Parkinson's disease (PD) ZnT proteins play an important role. Zinc is a co-factor of numerous enzymes and stabilizes the tertiary structure of several proteins. Nothing is known about previous infections mediated by Mycobacterium avium subsp. paratuberculosis (MAP). We evaluated if a previous infection with MAP could induce the production of antibodies that cross-reacted with the Znt homologous antigenic peptides associated to Parkinson. The humoral response toward MAP3865c peptides, ZnT3 and ZnT10 was evaluated. The hypothesis of cross-reactivity needs to be confirmed; we have observed the presence of MAP in PD patients by PCR, positivity to MAP3865c peptides, therefore MAP infection but not cross-reaction with human homologous Znt proteins.


Assuntos
Anticorpos Antibacterianos/imunologia , Imunoglobulina G/metabolismo , Mycobacterium avium subsp. paratuberculosis/imunologia , Doença de Parkinson/imunologia , Idoso , Estudos de Casos e Controles , Proteínas de Transporte de Cátions/imunologia , Reações Cruzadas/imunologia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/microbiologia , Peptídeos/imunologia , Curva ROC , Transportador 8 de Zinco
15.
J Neuroimmunol ; 291: 110-4, 2016 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-26857504

RESUMO

Environmental factors are implicated in the development of Parkinson's disease (PD). We have investigated on the role of molecular mimicry between HSV1 and α-synuclein that could foster the progression of PD. The antibody response against homologous peptides in PD patients and healthy controls was evaluated, showing that these antibodies are highly prevalent among PD patients to healthy controls. The competitive assay demonstrated cross-reactivity between HSV1 and human α-synuclein peptides. The results may suggest the hypothesis of the involvement of HSV1 in stimulating the immune cells against the neurons of the substantia nigra as a consequence of the cross reactivity.


Assuntos
Proteína Vmw65 do Vírus do Herpes Simples/metabolismo , Doença de Parkinson/complicações , alfa-Sinucleína/metabolismo , Idoso , Estudos de Casos e Controles , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mimetismo Molecular , Peptídeos/metabolismo , Curva ROC , Substância Negra/metabolismo , Substância Negra/patologia
16.
J Neurol Sci ; 357(1-2): 106-8, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26190523

RESUMO

Multiple Sclerosis (MS) is a heterogeneous disorder of the central nervous system (CNS) that begins as an inflammatory autoimmune disorder mediated by auto-reactive lymphocyte followed by microglial activation and chronic degeneration. The etiology of Multiple Sclerosis (MS) is unknown but several data support the hypothesis of possible infectious agents which may act as a trigger for the pathogenic cascade. Human endogenous retrovirus (HERV-W/MSRV), Epstein Barr Virus (EBV) and Mycobacterium avium ss. paratuberculosis (MAP) have been associated to Multiple Sclerosis. In this study, we evaluated the humoral response against different peptides: the human endogenous retrovirus HERV-Wenv73-88, MAP106c121-132 from MAP, EBNA1 400-413 from EBV and the homologous human peptide MBP85-98 in a cohort of MS patients treated with natalizumab. Results showed a statistically significant difference in the response against the HERV-W peptide in MS patients after two years of natalizumab treatment.


Assuntos
Retrovirus Endógenos/imunologia , Imunidade Humoral/imunologia , Esclerose Múltipla/tratamento farmacológico , Esclerose Múltipla/imunologia , Proteína Básica da Mielina/imunologia , Natalizumab/imunologia , Natalizumab/uso terapêutico , Oligopeptídeos/imunologia , Fragmentos de Peptídeos/imunologia , Adulto , Anticorpos/sangue , Estudos de Casos e Controles , Antígenos Nucleares do Vírus Epstein-Barr/imunologia , Feminino , Seguimentos , Produtos do Gene env/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas da Gravidez/imunologia , Adulto Jovem
17.
Mult Scler ; 20(2): 174-82, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23877972

RESUMO

BACKGROUND: Several viruses were reported as co-factors triggering the pathogenesis of multiple sclerosis (MS), including the endogenous retroviruses of the HERV-W family, that were also proposed as biomarkers of disease progression and therapy outcome. OBJECTIVE: The objective of this article is to clarify whether in MS patients treatment with natalizumab has effects on MSRV/syncytin-1/HERV-W expression and the possible relationship with disease outcome. METHODS: Peripheral blood mononuclear cells were collected from 22 patients with relapsing-remitting disease, at entry and after three, six and 12 months of treatment with natalizumab. The cell subpopulations and the expression of MSRVenv/syncytin-1/HERV-Wenv were analyzed by flow cytometry and by discriminatory env-specific RT-PCR assays. RESULTS: By flow cytometry the relative amounts of T, NK and monocyte subpopulations were shown to remain fairly constant. A relative increase of B lymphocytes was observed at three to six months (p = 0.033). The MSRVenv and syncitin-1 transcripts were reduced at six to 12 months of therapy (p = 0.0001). Accordingly, at month 12, the plasma-membrane levels of the HERV-Wenv protein were reduced (p = 0.0001). B cells, NK and monocytes but not T cells expressed the HERV-Wenv protein. None of the patients relapsed during therapy. CONCLUSION: Effective therapy with natalizumab downregulates MSRV/syncytin-1/HERV-W expression.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Retrovirus Endógenos/efeitos dos fármacos , Produtos do Gene env/análise , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/virologia , Proteínas da Gravidez/análise , Adulto , Estudos de Coortes , Feminino , Citometria de Fluxo , Humanos , Leucócitos Mononucleares/virologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Natalizumab , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto Jovem
19.
Dis Markers ; 35(3): 141-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24167359

RESUMO

BACKGROUND: Sulfhydryl groups (SH) are considered a key factor in redox sensitive reaction of plasma, and their modification could be considered an expression of abnormal generation of oxygen free radicals. METHODS: Fifty consecutive patients with acute brain stroke were enclosed in this study. The plasma concentrations of SH groups were correlated to cytokines (IL-1b, IL-6, IL-8, TNF- α ), plasma chitotriosidase (Chit), metalloprotease (MMP2-9), intercellular adhesion molecule-1 (ICAM-1). RESULTS: The results demonstrated a significant reduction of SH groups within 24 hours from the onset of an acute ischemic stroke, a reduction of plasma IL-1b, IL-6, and IL-8, and an increase of Chit and TNF- α in relation to the stroke severity. CONCLUSION: The observation of an intense microenvironment activation that follows the stroke and the correlation between SH levels and markers of immune response suggest that, especially in stroke, is necessary to maintain the redox function to prevent the brain damage. The reduced SH levels represent an attempt to neutralize the abnormal generation of free radicals. Since the reperfusion of brain after ischemic event represents a severe oxidative stress, which must be corrected by regeneration of redox sensitive function, pharmacological intervention could be beneficial in this setting.


Assuntos
Citocinas/sangue , Acidente Vascular Cerebral/sangue , Compostos de Sulfidrila/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Hexosaminidases/sangue , Humanos , Molécula 1 de Adesão Intercelular/sangue , Masculino , Metaloproteinases da Matriz/sangue , Pessoa de Meia-Idade , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/imunologia
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