Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 4.800
Filtrar
1.
Nat Med ; 25(12): 1865-1872, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31792456

RESUMO

Viruses are implicated in autoimmune destruction of pancreatic islet ß cells, which results in insulin deficiency and type 1 diabetes (T1D)1-4. Certain enteroviruses can infect ß cells in vitro5, have been detected in the pancreatic islets of patients with T1D6 and have shown an association with T1D in meta-analyses4. However, establishing consistency in findings across studies has proven difficult. Obstacles to convincingly linking RNA viruses to islet autoimmunity may be attributed to rapid viral mutation rates, the cyclical periodicity of viruses7 and the selection of variants with altered pathogenicity and ability to spread in populations. ß cells strongly express cell-surface coxsackie and adenovirus receptor (CXADR) genes, which can facilitate enterovirus infection8. Studies of human pancreata and cultured islets have shown significant variation in enteroviral virulence to ß cells between serotypes and within the same serotype9,10. In this large-scale study of known eukaryotic DNA and RNA viruses in stools from children, we evaluated fecally shed viruses in relation to islet autoimmunity and T1D. This study showed that prolonged enterovirus B rather than independent, short-duration enterovirus B infections may be involved in the development of islet autoimmunity, but not T1D, in some young children. Furthermore, we found that fewer early-life human mastadenovirus C infections, as well as CXADR rs6517774, independently correlated with islet autoimmunity.


Assuntos
Autoimunidade/imunologia , Diabetes Mellitus Tipo 1/virologia , Enterovirus/isolamento & purificação , RNA Viral/isolamento & purificação , Adolescente , Autoimunidade/genética , Criança , Pré-Escolar , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/patologia , Enterovirus/imunologia , Enterovirus/patogenicidade , Fezes/virologia , Feminino , Humanos , Lactente , Insulina/metabolismo , Células Secretoras de Insulina/imunologia , Células Secretoras de Insulina/virologia , Ilhotas Pancreáticas/imunologia , Ilhotas Pancreáticas/patologia , Ilhotas Pancreáticas/virologia , Masculino , Pâncreas/imunologia , Pâncreas/patologia , Pâncreas/virologia
2.
Isr Med Assoc J ; 21(7): 454-459, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31507120

RESUMO

BACKGROUND: Platelets have the ability to influence the immune system and the inflammatory process and may be strongly involved in the whole pathogenic process of chronic inflammatory joint diseases, such as rheumatoid arthritis. They may play a significant role even before the clinical onset of the disease, contributing to the loss of tolerance of the immune system and the induction of autoimmunity. Subsequently, they can interact with the most important cellular players involved in autoimmunity and inflammation, namely innate immunity cells and T cells and eventually contribute to the building of inflammation in the synovium, thus inducing the activation, migration, and proliferation of fibroblasts that eventually lead to joint damage. Due to their peculiar features, studying the behavior of platelets is a challenging task; however, platelets may prove to be valuable therapeutic targets in the future.


Assuntos
Artrite Reumatoide/imunologia , Plaquetas/imunologia , Sinovite/imunologia , Artrite Reumatoide/patologia , Autoimunidade/imunologia , Fibroblastos/imunologia , Humanos , Imunidade Inata/imunologia , Inflamação/imunologia , Inflamação/patologia , Membrana Sinovial/imunologia , Membrana Sinovial/patologia , Sinovite/patologia , Linfócitos T/imunologia
3.
Isr Med Assoc J ; 21(7): 480-486, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31507125

RESUMO

BACKGROUND: Serum rheumatoid factors are autoantibodies of different isotypes directed against the Fc fraction of immunoglobulin G (IgG) and represent paradigmatic autoantibodies that have been largely used in clinical practice for decades. Traditionally IgG has been associated with rheumatoid arthritis and more recently included also in the classification criteria for SjÓ§gren's syndrome. Researchers have established that rheumatoid factors are positive in a variety of infectious, autoimmune, and neoplastic disorders, thus requiring a comprehensive evaluation of seropositive patients. Of note, hepatitis B and C viruses represent a crossroad that includes the high rheumatoid factor seroprevalence and chronic inflammatory disease, as well as progression to non-Hodgkin's lymphomas. Chronic antigen stimulation is the likely common ground of these processes and rheumatoid factors may represent mere bystanders or drivers of pathology. Mixed cryoglobulinemia and lymphoproliferative disease are prime examples of the deleterious effects of rheumatoid factor-B cell activity, possibly associated with hepatitis B and C. More importantly, they show a clear association in a physiological host response to infection, chronic inflammation, and the slide toward autoimmunity and malignancy. The association between hepatitis B and C infections and the appearance of serum rheumatoid factors is further supported by prevalence data, which support a coexistence of these markers in a significant proportion of cases, with viral infections being frequent causes of rheumatoid factors in patients without a rheumatic condition. We provide a comprehensive overview of the known connections between hepatitis B and C infections and rheumatoid factors.


Assuntos
Hepatite B/imunologia , Hepatite C/imunologia , Fator Reumatoide/imunologia , Autoanticorpos/imunologia , Doenças Autoimunes/imunologia , Autoimunidade/imunologia , Crioglobulinemia/imunologia , Humanos , Transtornos Linfoproliferativos/imunologia , Neoplasias/imunologia , Fator Reumatoide/sangue
5.
Autoimmun Rev ; 18(10): 102367, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31404705

RESUMO

Aggregation of immuno-proteomic data reveals that i) herpesviruses and synaptic proteins -in particular Synapsin-1 and Bassoon - share a large number of hexapeptides that also recur in hundreds of epitopes experimentally validated as immunopositive in the human host, and ii) the shared peptides are also spread among human epilepsy-related proteins. The data indicate that cross-reactive processes may be associated with pathogenetic mechanisms in epilepsy, thus suggesting a role of autoimmunity in etiopathology of epilepsies after herpesvirus-infections.


Assuntos
Autoimunidade/imunologia , Epilepsia/etiologia , Epitopos/imunologia , Herpes Simples/complicações , Herpesviridae/imunologia , Fragmentos de Peptídeos/imunologia , Sinapsinas/imunologia , Animais , Reações Cruzadas , Epilepsia/patologia , Herpes Simples/imunologia , Humanos
6.
Int Arch Allergy Immunol ; 180(2): 150-158, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31284281

RESUMO

INTRODUCTION: Regulatory lymphocytes (CD4+ T regulatory cells [Treg], CD8+ Treg, and B regulatory cells [Breg]) play a critical role in immune homeostasis and tolerance. Common variable immunodeficiency (CVID) is associated with increased susceptibility to infections and increased frequency of inflammatory and autoimmune diseases. CD4+ Treg cell abnormalities have been reported in CVID; however, CD8+ Treg cells have not been reported in CVID. The objective of this study was to evaluate CD4+ Treg and CD8+ Treg cells in CVID patients. METHODS: In 25 patients with CVID and age-matched healthy controls, Treg cells, evaluated in freshly isolated peripheral blood mononuclear cells (natural; nCD4+ Treg and nCD8+ Treg) and following in vitro activation with anti-CD3/CD28 monoclonal antibodies (induced; iCD4+ Treg and iCD8+ Treg) as well as Breg cells were analyzed with specific monoclonal antibodies and isotype controls using flow cytometry. RESULTS: The proportions of nCD4+ Treg (CD4+ CD127low CD25high FoxP3+), iCD4+ Treg (CD4+ CD127low CD25high FoxP3+), iCD8+ Treg (CD8+ CD25high CD183+ FoxP3+), and Breg (CD19+ CD24high CD38high) lymphocytes were significantly lower in patients with CVID than in controls. CONCLUSIONS: Altered regulatory lymphocytes may play a role in the pathogenesis and autoimmunity and inflammation associated with CVID.


Assuntos
Linfócitos B Reguladores/imunologia , Linfócitos T CD8-Positivos/imunologia , Imunodeficiência de Variável Comum/imunologia , Linfócitos T Reguladores/imunologia , Adolescente , Adulto , Idoso , Envelhecimento/imunologia , Autoimunidade/imunologia , Feminino , Humanos , Inflamação/imunologia , Ativação Linfocitária/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
8.
EBioMedicine ; 45: 578-587, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31262710

RESUMO

BACKGROUND: Sphingomyelin synthase 1 (SMS1) has been reported to participate in hepatitis and atherosclerosis. However, its role in autoimmune response is not clear. This study investigates the possible involvement of SMS1 in B-cell activation and lupus-like autoimmunity. METHODS: SMS1 knockout lupus-like animal model and SLE patient samples were utilized. B-cell activation and associated signal transduction were detected by flow cytometry, confocal analysis and western blotting. The SMS1 expression in B cells was measured by real-time qPCR. FINDINGS: SMS1 deficiency suppressed B-cell activation in culture, which was restored by exogenous SM supplementation. The BCR-mediated early signal transduction including the colocalization of BCR with F-actin or pY/pBtk, and the phosphorylation of intracellular Fyn and Syk were impaired in SMS1 knockout B cells. Furthermore, SMS1 knockout mice showed reduced production and deposition of autoantibodies, accompanied by less severe kidney pathological changes after pristane induction. SMS1 deficiency also displayed lower autoantibody titers and 24 h urine protein excretion in bm12-induced lupus, which were associated with reduced B-cell activation. Adoptively transferred wide-type B cells partially recovered B-cell activation and autoantibody production in SMS1 deficient bm12-induced lupus mice. Moreover, the SMS1 mRNA level in B cells of SLE patients was increased and positively correlated with the serum anti-dsDNA level, IgG and globulin titers. INTERPRETATION: These data suggest that SMS1 is involved in lupus-like autoimmunity via regulating BCR signal transduction and B cell activation. (Word count for the abstract: 230).


Assuntos
Autoimunidade/genética , Linfócitos B/imunologia , Lúpus Eritematoso Sistêmico/genética , Transferases (Outros Grupos de Fosfato Substituídos)/genética , Actinas/genética , Animais , Autoanticorpos/genética , Autoanticorpos/imunologia , Autoimunidade/imunologia , Linfócitos B/metabolismo , Feminino , Citometria de Fluxo , Humanos , Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/patologia , Ativação Linfocitária/imunologia , Masculino , Camundongos , Camundongos Knockout
9.
Nat Commun ; 10(1): 3392, 2019 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-31358739

RESUMO

Autoreactivity to myeloperoxidase (MPO) causes anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), with rapidly progressive glomerulonephritis. Here, we show that a Staphylococcus aureus peptide, homologous to an immunodominant MPO T-cell epitope (MPO409-428), can induce anti-MPO autoimmunity. The peptide (6PGD391-410) is part of a plasmid-encoded 6-phosphogluconate dehydrogenase found in some S. aureus strains. It induces anti-MPO T-cell autoimmunity and MPO-ANCA in mice, whereas related sequences do not. Mice immunized with 6PGD391-410, or with S. aureus containing a plasmid expressing 6PGD391-410, develop glomerulonephritis when MPO is deposited in glomeruli. The peptide induces anti-MPO autoreactivity in the context of three MHC class II allomorphs. Furthermore, we show that 6PGD391-410 is immunogenic in humans, as healthy human and AAV patient sera contain anti-6PGD and anti-6PGD391-410 antibodies. Therefore, our results support the idea that bacterial plasmids might have a function in autoimmune disease.


Assuntos
Autoimunidade/imunologia , Proteínas de Bactérias/imunologia , Complexo Antigênico da Nefrite de Heymann/imunologia , Peptídeos/imunologia , Peroxidase/imunologia , Staphylococcus aureus/imunologia , Sequência de Aminoácidos , Animais , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/sangue , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/imunologia , Proteínas de Bactérias/genética , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Glomerulonefrite/imunologia , Complexo Antigênico da Nefrite de Heymann/metabolismo , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Peptídeos/genética , Peroxidase/metabolismo , Plasmídeos/genética , Staphylococcus aureus/genética , Staphylococcus aureus/fisiologia
10.
Nat Commun ; 10(1): 2377, 2019 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-31147550

RESUMO

Glycans from microbial pathogens are well known pathogen-associated molecular patterns that are recognized by the host immunity; however, little is known about whether and how mammalian self-glycans activate the host immune response, especially in the context of autoimmune disease. Using biochemical fractionation and two-dimensional HPLC, we identify an abundant and bioactive free glycan, the Manß1-4GlcNAc disaccharide in TREX1-associated autoimmune diseases. We report that both monosaccharide residues and the ß1-4 linkage are critical for bioactivity of this disaccharide. We also show that Manß1-4GlcNAc is produced by oligosaccharyltransferase hydrolysis of lipid-linked oligosaccharides in the ER lumen, followed by ENGase and mannosidase processing in the cytosol and lysosomes. Furthermore, synthetic Manß1-4GlcNAc disaccharide stimulates a broad immune response in vitro, which is in part dependent on the STING-TBK1 pathway, and enhances antibody response in vivo. Together, our data identify Manß1-4GlcNAc as a novel innate immune modulator associated with chronic autoimmune diseases.


Assuntos
Doenças Autoimunes/imunologia , Autoimunidade/imunologia , Dissacarídeos/imunologia , Imunidade Inata/imunologia , Proteínas de Membrana/imunologia , Proteínas Serina-Treonina Quinases/imunologia , Animais , Doenças Autoimunes/genética , Modelos Animais de Doenças , Retículo Endoplasmático , Exodesoxirribonucleases/genética , Fibroblastos , Camundongos , Fosfoproteínas/genética , Células RAW 264.7
11.
Nat Commun ; 10(1): 2603, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31197149

RESUMO

During thymic negative selection, autoreactive thymocytes carrying T cell receptor (TCR) with overtly strong affinity to self-MHC/self-peptide are removed by Bim-dependent apoptosis, but how Bim is specifically regulated to link TCR activation and apoptosis induction is unclear. Here we identify a murine T cell-specific genomic enhancer EBAB (Bub1-Acoxl-Bim), whose deletion leads to accumulation of thymocytes expressing high affinity TCRs. Consistently, EBAB knockout mice have defective negative selection and fail to delete autoreactive thymocytes in various settings, with this defect accompanied by reduced Bim expression and apoptosis induction. By contrast, EBAB is dispensable for maintaining peripheral T cell homeostasis via Bim-dependent pathways. Our data thus implicate EBAB as an important, developmental stage-specific regulator of Bim expression and apoptosis induction to enforce thymic negative selection and suppress autoimmunity. Our study unravels a part of genomic enhancer codes that underlie complex and context-dependent gene regulation in TCR signaling.


Assuntos
Autoimunidade/genética , Proteína 11 Semelhante a Bcl-2/genética , Elementos Facilitadores Genéticos/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Timócitos/fisiologia , Animais , Apoptose/genética , Apoptose/imunologia , Autoimunidade/imunologia , Proteína 11 Semelhante a Bcl-2/metabolismo , Sistemas CRISPR-Cas/genética , Elementos Facilitadores Genéticos/genética , Feminino , Regulação da Expressão Gênica/imunologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Modelos Animais , Receptores de Antígenos de Linfócitos T/imunologia , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Timo/citologia , Timo/imunologia
12.
Clin Lab ; 65(6)2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-31232027

RESUMO

BACKGROUND: To evaluate platelet functions in patients with Hashimoto's thyroiditis (HT) versus healthy controls. METHODS: Seventy-five patients with HT and 29 healthy controls were included in this study. Age, serum levels of thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), anti-thyroglobulin (anti-Tg) antibody and anti-thyroid peroxidase (anti-TPO) antibody, platelet count, in vitro platelet aggregation and ATP release reaction tests were recorded and compared between HT and control groups. RESULTS: Median (IQR) serum levels for TSH (p = 0.001), anti-TPO (p = 0.001), and anti-Tg (p = 0.001) antibodies were significantly higher, while FT4 levels (p = 0.005) were significantly lower in patients with HT than in controls. Patients had lower levels of ADP-induced platelet aggregation (p = 0.05) and lower ristocetin-induced ATP release activity (p = 0.05) compared to controls. Platelet count was positively correlated with serum FT4 levels (r = 0.27, p < 0.05). Conclusions: We found decreased ADP-induced platelet aggregation and ristocetin-induced platelet release activity as well as a positive correlation of platelet count with FT4 levels in patients with HT. Our findings support the role of thyroid hormone status and autoimmunity in the association between HT and platelet aggregation and secretion functions.


Assuntos
Autoimunidade/imunologia , Doença de Hashimoto/sangue , Contagem de Plaquetas , Testes de Função Plaquetária/métodos , Hormônios Tireóideos/sangue , Difosfato de Adenosina/farmacologia , Adulto , Autoanticorpos/sangue , Estudos Transversais , Doença de Hashimoto/imunologia , Humanos , Pessoa de Meia-Idade , Agregação Plaquetária/efeitos dos fármacos , Tireotropina/sangue
13.
Nat Immunol ; 20(8): 1046-1058, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31209405

RESUMO

The neonatal thymus generates Foxp3+ regulatory T (tTreg) cells that are critical in controlling immune homeostasis and preventing multiorgan autoimmunity. The role of antigen specificity on neonatal tTreg cell selection is unresolved. Here we identify 17 self-peptides recognized by neonatal tTreg cells, and reveal ligand specificity patterns that include self-antigens presented in an age- and inflammation-dependent manner. Fate-mapping studies of neonatal peptidyl arginine deiminase type IV (Padi4)-specific thymocytes reveal disparate fate choices. Neonatal thymocytes expressing T cell receptors that engage IAb-Padi4 with moderate dwell times within a conventional docking orientation are exported as tTreg cells. In contrast, Padi4-specific T cell receptors with short dwell times are expressed on CD4+ T cells, while long dwell times induce negative selection. Temporally, Padi4-specific thymocytes are subject to a developmental stage-specific change in negative selection, which precludes tTreg cell development. Thus, a temporal switch in negative selection and ligand binding kinetics constrains the neonatal tTreg selection window.


Assuntos
Autoantígenos/imunologia , Receptores de Antígenos de Linfócitos T alfa-beta/imunologia , Tolerância a Antígenos Próprios/imunologia , Linfócitos T Reguladores/citologia , Animais , Autoimunidade/imunologia , Diferenciação Celular/imunologia , Linhagem Celular , Feminino , Fatores de Transcrição Forkhead/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Desiminases de Arginina em Proteínas/metabolismo , Linfócitos T Reguladores/imunologia , Timo/citologia
14.
Expert Rev Clin Pharmacol ; 12(6): 513-521, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31035801

RESUMO

Introduction: Advanced cancers that did not respond to chemotherapy were once a death sentence, but now there are newer therapies utilizing the patient's own immune system to fight cancer that are proving effective in chemotherapy-refractory malignancies. However, this success against cancer cells may be accompanied by immune-related adverse events that can affect the kidneys. Areas covered: Using Medline and Scopus, we compiled all publications through February 2019 that pertained to immune checkpoint inhibitors (ICPIs) and chimeric antigen receptor T-cells (CAR T-cells).  The focus of this review is the discussion of these new cancer therapies, with attention to the reported kidney-related adverse effects.. Expert opinion: Autoimmunity is repressed by molecular pathways that inhibit T-cell activation against selected antigens. These self-protective mechanisms have been appropriated by tumor cells as a means of evading immune detection and destruction. New immunotherapies such as immune checkpoint inhibitors and chimeric antigen receptor T-cell therapy incite an aggressive immune response directed against tumor cells. This unrestrained activation of the immune system may result in kidney injury via multiple mechanisms.


Assuntos
Imunoterapia/efeitos adversos , Nefropatias/etiologia , Neoplasias/terapia , Autoimunidade/imunologia , Humanos , Imunoterapia/métodos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Nefropatias/imunologia , Neoplasias/imunologia
15.
Cells ; 8(5)2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-31052239

RESUMO

The Hippo pathway was originally identified as an evolutionarily-conserved signaling mechanism that contributes to the control of organ size. It was then rapidly expanded as a key pathway in the regulation of tissue development, regeneration, and cancer pathogenesis. The increasing amount of evidence in recent years has also connected this pathway to the regulation of innate and adaptive immune responses. Notably, the Hippo pathway has been revealed to play a pivotal role in adaptive immune cell lineages, as represented by the patients with T- and B-cell lymphopenia exhibiting defective expressions of the pathway component. The complex regulatory mechanisms of and by the Hippo pathway have also been evident as alternative signal transductions are employed in some immune cell types. In this review article, we summarize the current understanding of the emerging roles of the Hippo pathway in adaptive immune cell development and differentiation. We also highlight the recent findings concerning the dual functions of the Hippo pathway in autoimmunity and anti-cancer immune responses and discuss the key open questions in the interplay between the Hippo pathway and the mammalian immune system.


Assuntos
Imunidade Adaptativa/imunologia , Autoimunidade/imunologia , Linfopenia/imunologia , Mamíferos/imunologia , Neoplasias/imunologia , Proteínas Serina-Treonina Quinases/imunologia , Animais , Diferenciação Celular/imunologia , Drosophila/metabolismo , Humanos , Linfócitos T/citologia , Linfócitos T/imunologia
16.
Eur Cytokine Netw ; 30(1): 1-14, 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31074417

RESUMO

Guillain-Barré syndrome (GBS) is the most common cause of acute paralysis in the United States. Campylobacter jejuni is a common trigger for GBS, igniting autoimmunity as a result of molecular mimicry between C. jejuni lipooligosaccharide (LOS) and host gangliosides. Evidence also suggests an active role for cell-mediated and innate immunity in pathogenesis of GBS. Infection alone is not enough for GBS to develop, infection with the same strain might yield different outcomes in different patients. C. jejuni strains with low to absent molecular mimicry to self-antigens can cause full-blown GBS with positive autoantibodies. A role for T helper 17 and IL-17 in acute phase of GBS is also identified. Currently, no biological treatment is validated for severe, ventilation-dependent patients with GBS, who might not benefit from either IVIG or plasma exchange therapy. Use of biologic agents in treatment-resistant GBS, especially anti-IL-17 agents, such as secukinumab, ixekizumab, and brodalumab, is to be hoped. This review covers up-to-date knowledge on autoimmune mechanisms responsible in different subtypes of GBS: acute inflammatory demyelinating polyneuropathy and acute motor axonal neuropathy; as well as the experimental autoimmune neuritis (EAN), a commonly used animal model of GBS.


Assuntos
Autoimunidade/imunologia , Campylobacter jejuni/imunologia , Citocinas/imunologia , Síndrome de Guillain-Barré/imunologia , Mimetismo Molecular/imunologia , Animais , Anticorpos Monoclonais/uso terapêutico , Autoanticorpos/imunologia , Infecções por Campylobacter/imunologia , Infecções por Campylobacter/microbiologia , Gangliosídeos/imunologia , Síndrome de Guillain-Barré/tratamento farmacológico , Síndrome de Guillain-Barré/patologia , Humanos , Interleucina-17/imunologia , Lipopolissacarídeos/imunologia , Camundongos , Células Th17/imunologia
17.
J Immunoassay Immunochem ; 40(4): 343-349, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31116079

RESUMO

Reactive oxygen species (ROS) are implicated in inflammatory, autoimmune, and neurodegenerative diseases. The activation, proliferation, and apoptosis of immune cells are dependent on the controlled production and elimination of ROS. However, under chronic inflammatory conditions, large amounts of ROS generated are a major cause of many human diseases. The electronically excited molecular oxygen species known as singlet oxygen (1O2) is a form of ROS and is one of the major cytotoxic species in eukaryotic cells. ROS are known to cause DNA damage leading to strand breaks, base damage, and conformational changes. The 1O2, being one of the most potent ROS, is generated by photoexcitation or by chemiexcitation and is known to selectively react with the deoxyguanosine moiety in DNA. The biological consequences of 1O2-induced damage causes loss of transforming activity as well as mutagenicity and genotoxicity and may lead to the formation of neo-epitopes in native DNA and generation of pathogenic anti-DNA antibodies. The excessive production of ROS may be one of the factors responsible for the induction of autoimmune response in diseases such as cancer and systemic lupus erythematosus. Abbreviations: Singlet oxygen: 1O2; Superoxide anion: O2-.; Hydroxyl radical: OH; Hydrogen peroxide: H2O2.


Assuntos
Lúpus Eritematoso Sistêmico/imunologia , Lúpus Eritematoso Sistêmico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Oxigênio Singlete/metabolismo , Anticorpos Antinucleares/imunologia , Autoimunidade/imunologia , Humanos
18.
Autoimmun Rev ; 18(6): 565-575, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30959209

RESUMO

Psoriatic arthritis (PsA) is a chronic inflammatory arthritis that may be present in near 30% of patients affected by psoriasis (PsO), clinically characterized by inflammation of periarticular (e.g., enthesis) and articular structures. Recently, an autoimmune footprint of PsA pathogenesis has been demonstrated with the presence of autoantigens and related autoantibodies in PsA patients' sera. In this context, histological features of PsA synovitis supports the relevance of an autoimmune pathogenesis of the disease. Since there is no currently validated test for PsA, the analysis of PsA synovial tissue revealed pathognomonic characteristics of PsA that may support the clinician in the clinical practice. PsA synovitis is characterized by a sublining infiltrate with T and B cells, vascular proliferation and a relative thin lining layer of proliferating intimal synoviocytes. PsA synovial histopathology shows that ectopic lymphoid-neogenesis with an increase of IL-23 expression. These new pathogenetics features and the systemic nature of the disease raised the concept of a Systemic Psoriatic Disease (SysPsD), characterized by multiple extra-cutaneous and -articular manifestations, highlightening the great heterogeneity of this condition. SyPsD represents a heterogeneous chronic inflammatory condition with a wide spectrum of phenotypical manifestations. The purpose of this review is to describe the new pathogenetic mechanisms and the different clinical pictures of SysPsD, with the ultimate goal of improving the knowledge of this heterogeneous chronic inflammatory condition.


Assuntos
Artrite Psoriásica/imunologia , Autoimunidade/imunologia , Humanos
19.
J Immunol Res ; 2019: 8016254, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30944838

RESUMO

As the most abundant leukocytes in the circulation, neutrophils are committed to innate and adaptive immune effector function to protect the human body. They are capable of killing intruding microbes through various ways including phagocytosis, release of granules, and formation of extracellular traps. Recent research has revealed that neutrophils are heterogeneous in phenotype and function and can display outstanding plasticity in both homeostatic and disease states. The great flexibility and elasticity arm neutrophils with important regulatory and controlling functions in various disease states such as autoimmunity and inflammation as well as cancer. Hence, this review will focus on recent literature describing neutrophils' variable and diverse phenotypes and functions in different contexts.


Assuntos
Imunidade Adaptativa , Imunidade Inata , Neutrófilos/imunologia , Fenótipo , Autoimunidade/imunologia , Armadilhas Extracelulares/imunologia , Homeostase/imunologia , Humanos , Inflamação , Neoplasias/imunologia , Ativação de Neutrófilo/imunologia , Neutrófilos/fisiologia , Fagocitose/imunologia
20.
Blood ; 133(24): 2586-2596, 2019 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-31015189

RESUMO

DiGeorge syndrome (DGS) is a primary immunodeficiency characterized by various degrees of T-cell deficiency. In partial DGS (pDGS), other risk factors could predispose to recurrent infections, autoimmunity, and allergy. The aim of this study was to assess the effect of different factors in the development of infections, autoimmunity, and/or allergy in patients with pDGS. We studied 467 pDGS patients in follow-up at Great Ormond Street Hospital. Using a multivariate approach, we observed that palatal anomalies represent a risk factor for the development of recurrent otitis media with effusion. Gastroesophageal reflux/dysphagia and asthma/rhinitis represent a risk factor for the development of recurrent upper respiratory tract infections. Allergy and autoimmunity were associated with persistently low immunoglobulin M levels and lymphopenia, respectively. Patients with autoimmunity showed lower levels of CD3+, CD3+CD4+, and naïve CD4+CD45RA+CD27+ T lymphocytes compared with pDGS patients without autoimmunity. We also observed that the physiological age-related decline of the T-cell number was slower in pDGS patients compared with age-matched controls. The age-related recovery of the T-cell number depended on a homeostatic peripheral proliferation of T cells, as suggested by an accelerated decline of the naïve T lymphocytes in pDGS as well as a more skewed T-cell repertoire in older pDGS patients. These evidences suggest that premature CD4+ T-cell aging and lymphopenia induced spontaneous peripheral T-cell proliferation might contribute to the pathogenesis of autoimmunity in patients with pDGS. Infections in these patients represent, in most of the cases, a complication of anatomical or gastroenterological anomalies rather than a feature of the underlying immunodeficiency.


Assuntos
Autoimunidade/imunologia , Síndrome de DiGeorge/imunologia , Síndrome de DiGeorge/patologia , Adolescente , Adulto , Autoimunidade/genética , Criança , Pré-Escolar , Síndrome de DiGeorge/complicações , Feminino , Humanos , Lactente , Masculino , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA