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1.
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
2.
Expert Opin Ther Pat ; 29(9): 663-674, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31403347

RESUMO

Introduction: RORγt is critical for the differentiation of Th17 cells and the production of IL-17. Inhibition of RORγt is considered as a promising strategy to treat Th17-mediated autoimmune diseases. Quite a number of RORγt inhibitors have been progressed into clinical trials, besides much biological interests in this attractive target. Areas covered: This article reviews the progress of RORγt inhibitors (antagonists and inverse agonists) that are active in clinical development based on an analysis of the related patents published by the corresponding companies in the period of January 2016 through May 2019. Expert opinion: The development of RORγt inhibitors has gone through a boom period in the past three years. However, with a little bit frustration, some of the frontrunner clinical compounds were either discontinued or suspended for further development possibly due to some safety concerns or lack of efficacy in humans. There is a need to probe deeply into these concerns in the on-going pre-clinical and clinical studies. Given the effectiveness of a few recently FDA-approved anti-IL-17(R) antibodies on psoriasis, the discovery of RORγt inhibitors continues to be an exciting field for the development of novel treatment approaches.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Desenvolvimento de Medicamentos/métodos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/antagonistas & inibidores , Animais , Doenças Autoimunes/imunologia , Descoberta de Drogas , Humanos , Interleucina-17/imunologia , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/imunologia , Patentes como Assunto , Células Th17/imunologia
3.
Vet Immunol Immunopathol ; 214: 109902, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31378221

RESUMO

Autoantibodies against cytokines have been associated with immunodeficiency, susceptibility to infectious diseases, autoimmunity and inflammation in humans, but have not yet been investigated in the Veterinary field so far. The aim of the current study was to determine the presence of anti-cytokine autoantibodies in canines suffering from various conditions including recurrent infections, autoimmune diseases and cancer in comparison to healthy controls. This is the first report of the presence of autoantibodies against cytokines in dogs. A total of 101 serum samples (51 patients and 50 clinically healthy dogs) from the state of Mexico and surroundings were analysed using a multiplex bead-based flow cytometry assay. Results show significant levels of various anti-cytokine autoantibodies in diseased dogs but not in healthy controls. In addition we show distinct associations of various disease types to the specificity of anti-cytokine autoantibodies and to response complexities. Apart from the direct functional/causal implication of anti-cytokine auto-antibodies on disease processes, this findings point to the possibility to use anti-cytokine response patterns as diagnostic tools.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/veterinária , Citocinas/imunologia , Doenças do Sistema Imunitário/veterinária , Animais , Doenças Autoimunes/imunologia , Cães , Feminino , Doenças do Sistema Imunitário/imunologia , Incidência , Masculino , México , Neoplasias/imunologia , Neoplasias/veterinária
5.
Pan Afr Med J ; 32: 181, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31312295

RESUMO

Introduction: The term anti-nuclear antibody (ANA) is used to define a large group of autoantibodies which specifically bind to nuclear elements. Although healthy individuals may also have ANA positivity, the measurement of ANA is generally used in the diagnosis of autoimmune disorders. However, various studies have shown that ANA testing may be overused, especially in pediatrics clinics. Our aim was to investigate the reasons for antinuclear antibody (ANA) testing in the general pediatrics and pediatric rheumatology clinics of our hospital and to determine whether ANA testing was ordered appropriately by evaluating chief complaints and the ultimate diagnoses of these cases. Methods: The medical records of pediatric patients in whom ANA testing was performed between January 2014 and June 2016 were retrospectively evaluated. Subjects were grouped according to the indication for ANA testing and ANA titers. Results: ANA tests were ordered in a total of 409 patients during the study period, with 113 positive ANA results. The ANA test was ordered mostly due to joint pain (50% of the study population). There was an increased likelihood of autoimmune rheumatic diseases (ARDs) with higher ANA titer. The positive predictive value of an ANA test was 16% for any connective tissue disease and 13% for lupus in the pediatric setting. Conclusion: in the current study, more than one-fourth of the subjects were found to have ANA positivity, while only 15% were ultimately diagnosed with ARDs. Our findings underline the importance of an increased awareness of correct indications for ANA testing.


Assuntos
Anticorpos Antinucleares/sangue , Doenças Autoimunes/diagnóstico , Doenças do Tecido Conjuntivo/diagnóstico , Doenças Reumáticas/diagnóstico , Adolescente , Instituições de Assistência Ambulatorial , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/imunologia , Criança , Pré-Escolar , Doenças do Tecido Conjuntivo/epidemiologia , Doenças do Tecido Conjuntivo/imunologia , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/epidemiologia , Lúpus Eritematoso Sistêmico/imunologia , Masculino , Valor Preditivo dos Testes , Estudos Retrospectivos , Doenças Reumáticas/epidemiologia , Doenças Reumáticas/imunologia , Turquia/epidemiologia
6.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 41(3): 344-350, 2019 Jun 30.
Artigo em Chinês | MEDLINE | ID: mdl-31282328

RESUMO

Objective To explore the clinical characteristics of autoimmune disease with dual seropositive antibodies of leucine-rich glioma inactivated 1(LGI1)and contactin-associated protein 2(Caspr2).Methods The clinical data of seven patients with dual seropositive LGI1 and Caspr2 antibodies who were admitted to the Neurology Department of Peking Union Medical College Hospital from July 2014 to December 2017 were retrospectively analyzed.Results Central,peripheral and autonomic nervous systems were all involved in the seven cases;100%(7/7)presented with insomnia,myokymia,neuropahic pain and hyperhydrosis;71%(5/7)showed memory decline or psychiatric and behavioral symptoms;57%(4/7)had urinary hesitation or constipation;and 43%(3/7)had seizure.Electromyography showed 100%(6/6) of the patients had prolonged afterdischarges following normal M waves and/or abnormal spontaneous firing.Electroencephalography revealed slow waves or basic rhythm slowing in 71%(5/7)of patients.Electrocardiography showed sinus tachycardia,axis deviation,and prolonged QT intervals in 71%(5/7)of patients.One patient died from arrhythmia before immunotherapy.One died from pulmonary infection after immunotherapy.Improvement with immunotherapy was documented in the other five cases.No relapse was noted during the 1-2-year follow-up.Conclusions Autoimmune disease with dual seropositive antibodies of LGI1 and Caspr2 can diffusely affect the central,peripheral,and autonomic nervous systems.The possibility of this disease should be considered in patients with acute and subacute onset of neuropsychiatric symptoms,especially in patients with accompanying insomnia,myokymia,and hyperhydrosis.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/imunologia , Proteínas de Membrana/imunologia , Proteínas do Tecido Nervoso/imunologia , Proteínas/imunologia , Humanos , Estudos Retrospectivos
7.
Scand J Immunol ; 90(4): e12803, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31267615

RESUMO

Anti-centrosome antibodies are rare findings with undefined clinical significance in clinical research. We aimed at investigating the prevalence and clinical significance of anti-centrosome antibodies in Chinese population. Testing results of total of 281,230 ANA-positive sera were retrospectively obtained from West China Hospital Sichuan University in China between 2008 and 2017. We retrospectively collected and analysed the clinical and laboratory data of the patients with positive anti-centrosome antibody. Of the 356 453 patients tested, 281 230 patients had positive antinuclear antibodies (ANAs, 78.9%), but only 78 patients with positive anti-centrosome antibodies (0.022%), of which 74.4% are females. Diagnoses were established in 69 of 78 patients: 37 cases were autoimmune diseases, mainly including undifferentiated connective tissue diseases (UCTD, 9/37), rheumatoid arthritis (RA, 6/37), Sjögren's syndrome (SS, 5/37) and primary biliary cirrhosis (PBC, 5/37), and the remaining were other autoimmune conditions. The most frequent clinical symptoms of the anti-centrosome-positive patients were arthralgia and eyes and mouth drying. Additionally, 86.7% of anti-centrosome antibodies were not associated with other ANA profiles; however, when associated, the most frequent ANA was anti-U1RNP. Anti-centrosome antibodies are featured by a low prevalence and female gender predominance. They are correlated with some specific diseases, both autoimmune diseases, especially UCTD, RA, SS and PBC, and non-autoimmune diseases, such as infection and cancer, which suggests that they might be potential supporting serological markers of these diseases.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/imunologia , Centrossomo/imunologia , Tecido Conjuntivo/imunologia , Fatores Sexuais , Adulto , Anticorpos Antinucleares/sangue , Artralgia , Doenças Autoimunes/epidemiologia , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos
8.
Biochemistry (Mosc) ; 84(Suppl 1): S193-S205, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31213202

RESUMO

Cytokines of the IL-17 family play a key role in the host organism defense against bacterial and fungal infections. At the same time, upregulated synthesis of IL-17 cytokines is associated with immunoinflammatory and autoimmune diseases such as psoriasis, rheumatoid arthritis, systemic lupus erythematosus, and others. The members of this family are important therapeutic targets in the treatment of various human chronic inflammatory disorders. Elucidation of signaling pathways involving IL-17 family proteins and analysis of the structure of cytokine complexes with specific antibodies, inhibitors, and receptors are essential for the development of new drugs for the therapy of immunoinflammatory rheumatic diseases.


Assuntos
Doenças Autoimunes/imunologia , Interleucina-17 , Terapia de Alvo Molecular , Linfócitos T/imunologia , Anticorpos Monoclonais/farmacologia , Humanos , Interleucina-17/antagonistas & inibidores , Interleucina-17/química , Interleucina-17/fisiologia , Estrutura Quaternária de Proteína , Transdução de Sinais
9.
Zhonghua Gan Zang Bing Za Zhi ; 27(5): 393-396, 2019 May 20.
Artigo em Chinês | MEDLINE | ID: mdl-31177668

RESUMO

Autoimmune cholangitis (AIC) was first reported in 1987 as a chronic cholestatic disease that occurs predominantly in middle-aged women and has a common clinical manifestations, biochemical abnormalities and pathological changes with primary biliary cholangitis (PBC). However, serum anti-mitochondrial antibodies (AMA) are negative, and ANA and/or smooth muscle antibody positive rates are higher. The treatment response and prognosis with ursodeoxycholic acid and steroids is poor, thus it needs to be treated with immunosuppressive agents. Presently, the exact pathological mechanism of AIC is still unclear, and there is no unified assertion that classifies it as a new autoimmune liver disease or AMA-negative PBC. This article reviews the worldwide published work on AIC and compares them with PBC.


Assuntos
Autoanticorpos/imunologia , Doenças Autoimunes/patologia , Colangite/patologia , Cirrose Hepática Biliar/imunologia , Anticorpos Antinucleares/imunologia , Doenças Autoimunes/imunologia , Colangite/imunologia , Feminino , Humanos , Pessoa de Meia-Idade
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.
Clin Ter ; 170(3): e211-e215, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31173052

RESUMO

Different studies investigated about the role of T-helper 1 cytokines and chemokines in primary biliary cirrhosis (PBC). Animal models with autoimmune cholangitis have been used to investigate the involvement of (C-X-C motif) receptor (CXCR)3 and its ligand (C-X-C motif) ligand (CXCL)9/monokine induced by interferon (IFN)-γ (MIG) in the pathogenesis of PBC, suggesting a contribution of MIG in the development of PBC. In patients with PBC, in particular at the level of the portal areas of diseased livers, MIG expression and CXCR3+ cells have been found. MIG is positively associated with the severity of liver fibrosis. In PBC, circulating MIG levels and CXCR3+ cells are related with the progression of the disease; in fact, their expression increases significantly in PBC patients with respect to controls. Furthermore, it has been shown a significant reduction of these chemokines in the serum of PBC patients after treatment with ursodeoxycholic acid.


Assuntos
Quimiocina CXCL9/sangue , Cirrose Hepática Biliar/sangue , Receptores CXCR3/sangue , Animais , Doenças Autoimunes/imunologia , Quimiocina CXCL10/sangue , Quimiocinas/sangue , Colangite/sangue , Citocinas/sangue , Progressão da Doença , Humanos , Ácido Ursodesoxicólico/administração & dosagem
12.
Life Sci ; 231: 116593, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31228512

RESUMO

Inflammasomes are the major mechanistic complexes that include members of the NOD-like receptor (NLRs) or AIM2-like receptors (ALRs) families, which are affiliated with the innate immune system. Once NLRs or ALRs are activated by pathogen-associated molecular patterns (PAMPs) or damage-associated molecular patterns (DAMPs), the caspase-1 or -11 is activated by binding with NLRs or ALRs via its own unique cytosolic domains. As a result, caspase-1 or -11 enhances the production of IL-1ß and IL-18, which results in inflammation via the recruitment of immune cells, such as macrophages, and the promotion of programmed cell death mechanisms such as pyroptosis. In addition, the consistent cascades of inflammasomes would precede both minor and severe autoimmune diseases and cancers. The clinical relevance of inflammasomes in multiple forms of cancer highlights their therapeutic promise as molecular targets. To closely analyze the physiological roles of inflammasomes in cancers, here, we describe the fundamental knowledge regarding the current issues of inflammasomes in relevant cancers, and discuss possible therapeutic values in targeting these inflammasomes for the prevention and treatment of cancer.


Assuntos
Inflamassomos/metabolismo , Inflamassomos/fisiologia , Neoplasias/terapia , Alarminas/metabolismo , Animais , Apoptose/fisiologia , Doenças Autoimunes/imunologia , Proteínas de Transporte/metabolismo , Caspase 1/metabolismo , Caspases/metabolismo , Humanos , Imunidade Inata/imunologia , Inflamação/imunologia , Interleucina-18/metabolismo , Interleucina-1beta/metabolismo , Proteínas NLR/fisiologia , Padrões Moleculares Associados a Patógenos/metabolismo , Transdução de Sinais
13.
Scand J Immunol ; 90(3): e12799, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31211854

RESUMO

Pemphigus vulgaris (PV) is an autoimmune disease characterized by the production of IgG autoantibodies owing to an imbalance in the Th1/Th2 and Th17/Tregs cell pathways. The role of gut microbiota in the development of immune system and autoimmune diseases has been unraveled in the last two decades. However, data pertaining to gut microbiota of PV patients is largely lacking. We aimed to compare the gut microbiota of PV patients and healthy controls and assessed potential correlation with circulating cytokines of Th1/Th2/Th17 cell. Faecal bacterial diversity was analysed in 18 PV patients and 14 age- and gender-matched healthy individuals using hypervariable tag sequencing of the V3-V4 region of the 16S rRNA gene. Plasma levels of 20 inflammatory cytokines were assessed using the Luminex screening system. As a result, we identified 10 differentially abundant taxa between patients and controls. At the genera level, Lachnospiracea_incertae_sedis and Coprococcus decreased, while Granulicatella, Flavonifractor enriched in PV. Plasma levels of C5a, interleukin (IL)-2R, IL-6, IL-8, IL-7, IL-1ß, IL17A, IL-5 and IL-21 were significantly increased in PV Flavonifractor exhibited a positive correlation with C5a, IL-6, IL-8, IL-7, IL-1ß, IL17A and IL-21. Lachnospiracea_incertae_sedis and Coprococcus showed a negative correlation with IL-17A. Our results are consistent with the hypothesis that PV patients have gut microbial dysbiosis which might contribute to the immune disorder and the development of PV.


Assuntos
Doenças Autoimunes/imunologia , Citocinas/imunologia , Microbioma Gastrointestinal/imunologia , Inflamação/imunologia , Pênfigo/imunologia , Plasma/imunologia , Adulto , Autoanticorpos/imunologia , Doenças Autoimunes/microbiologia , Fezes/microbiologia , Feminino , Humanos , Inflamação/microbiologia , Masculino , Pessoa de Meia-Idade , Pênfigo/microbiologia , Plasma/microbiologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/microbiologia , Células Th1/imunologia , Células Th1/microbiologia , Células Th17/imunologia , Células Th17/microbiologia , Células Th2/imunologia , Células Th2/microbiologia
14.
Nat Commun ; 10(1): 2150, 2019 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-31089130

RESUMO

Peptide-major histocompatibility complex class II (pMHCII)-based nanomedicines displaying tissue-specific autoantigenic epitopes can blunt specific autoimmune conditions by re-programming cognate antigen-experienced CD4+ T-cells into disease-suppressing T-regulatory type 1 (TR1) cells. Here, we show that single pMHCII-based nanomedicines displaying epitopes from mitochondrial, endoplasmic reticulum or cytoplasmic antigens associated with primary biliary cholangitis (PBC) or autoimmune hepatitis (AIH) can broadly blunt PBC, AIH and Primary Sclerosing Cholangitis in various murine models in an organ- rather than disease-specific manner, without suppressing general or local immunity against infection or metastatic tumors. Therapeutic activity is associated with cognate TR1 cell formation and expansion, TR1 cell recruitment to the liver and draining lymph nodes, local B-regulatory cell formation and profound suppression of the pro-inflammatory capacity of liver and liver-proximal myeloid dendritic cells and Kupffer cells. Thus, autoreactivity against liver-enriched autoantigens in liver autoimmunity is not disease-specific and can be harnessed to treat various liver autoimmune diseases broadly.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Antígenos de Histocompatibilidade Classe II/imunologia , Hepatopatias/tratamento farmacológico , Nanopartículas/administração & dosagem , Peptídeos/administração & dosagem , Idoso , Animais , Autoantígenos/imunologia , Doenças Autoimunes/imunologia , Linhagem Celular , Modelos Animais de Doenças , Epitopos/imunologia , Feminino , Antígenos de Histocompatibilidade Classe II/química , Humanos , Fígado/efeitos dos fármacos , Fígado/imunologia , Hepatopatias/imunologia , Masculino , Camundongos , Pessoa de Meia-Idade , Nanomedicina/métodos , Nanopartículas/química , Peptídeos/química , Peptídeos/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia
15.
Nat Commun ; 10(1): 2261, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113940

RESUMO

Cyclic GMP-AMP synthase (cGAS) is the primary sensor for aberrant intracellular dsDNA producing the cyclic dinucleotide cGAMP, a second messenger initiating cytokine production in subsets of myeloid lineage cell types. Therefore, inhibition of the enzyme cGAS may act anti-inflammatory. Here we report the discovery of human-cGAS-specific small-molecule inhibitors by high-throughput screening and the targeted medicinal chemistry optimization for two molecular scaffolds. Lead compounds from one scaffold co-crystallize with human cGAS and occupy the ATP- and GTP-binding active site. The specificity and potency of these drug candidates is further documented in human myeloid cells including primary macrophages. These novel cGAS inhibitors with cell-based activity will serve as probes into cGAS-dependent innate immune pathways and warrant future pharmacological studies for treatment of cGAS-dependent inflammatory diseases.


Assuntos
Descoberta de Drogas/métodos , Inibidores Enzimáticos/farmacologia , Nucleotidiltransferases/antagonistas & inibidores , Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/imunologia , Doenças Autoimunes/patologia , Células Cultivadas , Cristalografia por Raios X , DNA/imunologia , DNA/metabolismo , Inibidores Enzimáticos/química , Inibidores Enzimáticos/uso terapêutico , Ensaios de Triagem em Larga Escala/métodos , Humanos , Imunidade Inata/efeitos dos fármacos , Interferons/imunologia , Interferons/metabolismo , Macrófagos , Modelos Moleculares , Nucleotídeos Cíclicos/imunologia , Nucleotídeos Cíclicos/metabolismo , Nucleotidiltransferases/imunologia , Nucleotidiltransferases/isolamento & purificação , Nucleotidiltransferases/metabolismo , Cultura Primária de Células , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/isolamento & purificação , Proteínas Recombinantes/metabolismo
16.
Graefes Arch Clin Exp Ophthalmol ; 257(8): 1759-1764, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31119427

RESUMO

PURPOSE: To explore the presence of serum anti-retinal antibodies (ARAs) in the Chinese patients with presumed autoimmune retinopathy (AIR). METHODS: Twenty-three Chinese patients with presumed AIR, disease controls including 40 RP patients, 22 bilateral uveitis patients, 18 acute zonal outer occult retinopathy (AZOOR) patients, and 30 healthy donors were included. Serum samples of all the subjects were obtained and analyzed for the presence of four ARAs including recoverin, α-enolase, carbonic anhydraseII (CAII), and collapsin response-mediated protein (CRMP)-5 by Western bolt assay. RESULTS: ARAs were present in the serum of either presumed AIR patients, disease control, or healthy donors. One or more ARAs were present in the 78.2% of presumed AIR while they were indicated in the 35.0% of RP patients (p < 0.01) and 33.3% of healthy donors (p < 0.01). The prevalence of ARAs in the bilateral uveitis and AZOOR was 63.3% and 100% respectively. Positive rate of α-enolase antibody present in the presumed AIR, disease control, and healthy donors was 73.9%, 47.5%, and 33.3% respectively. Positive rate of CAII antibody present above groups was 52.1%, 50%, and 33.3% respectively. Recoverin antibody seemed to be specifically present in the serum of patients with cancer-associated retinopathy. CONCLUSION: Presence of serum ARAs including recoverin, α-enolase, CAII, or CRMP-5 in the Chinese patients with presumed AIR occurred significantly more often than RP patients and healthy donors. Seropositivity of ARAs had diagnostic value for the presumed AIR but mere presence was not sufficient for the diagnosis due to identification of them in the healthy controls and other retinal diseases.


Assuntos
Autoanticorpos/sangue , Doenças Autoimunes/imunologia , Retina/imunologia , Doenças Retinianas/imunologia , Adulto , Idoso , Doenças Autoimunes/sangue , Doenças Autoimunes/epidemiologia , Western Blotting , Anidrase Carbônica II/sangue , Anidrase Carbônica II/imunologia , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/sangue , Proteínas do Tecido Nervoso/imunologia , Fosfopiruvato Hidratase/sangue , Fosfopiruvato Hidratase/imunologia , Prevalência , Recoverina/sangue , Recoverina/imunologia , Doenças Retinianas/sangue , Doenças Retinianas/epidemiologia , Estudos Retrospectivos
17.
Wiad Lek ; 72(4): 716-722, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31055563

RESUMO

OBJECTIVE: Introduction: Autoimmune uveitis (AU) is an inflammation of the uvea due to an autoimmune reaction to self-antigens. There are no standardized treatment protocols for AU. A new class of drugs called biologics, that target the various mediators of the inflammation cascade, may potentially provide more effective and less toxic corticosteroids treatment of AU. The aim: The aim of this review was to make the evaluatation of the interleukins influence on intraocular inflammation in available literature and summarize the expediency of using anti-interleukins agent in case of AU. PATIENTS AND METHODS: Material and methods: This article is a review and summary of the up-to-date results of pivotal experimental and clinical trials targeting the Interleukins (IL), including IL-6, IL-10, IL-17, IL-22, IL-23, and tumor necrosis factor alpha (TNF-α). Also reviews focus on the potential use of anti-interleukin therapy for the treatment of autoimmune diseases (AD). CONCLUSION: Conclusions: AU is an inflammation of the uvea due to an autoimmune reaction to self-antigens. The most important IL in the pathogenesis of AU are IL-6, IL-10, IL-17, IL-22, IL-23 and TNF-α. Anti-interleukin therapy is partially described. Future randomized controlled trials are urgently needed to be conduct.


Assuntos
Doenças Autoimunes/imunologia , Interleucinas/imunologia , Uveíte/imunologia , Humanos , Inflamação/imunologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Fator de Necrose Tumoral alfa/imunologia
18.
Autoimmun Rev ; 18(7): 647-657, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059841

RESUMO

In addition to protecting body from infections and diseases, the immune system produces auto-antibodies that can cause complex autoimmune disorders, such as Type I diabetes, primary biliary cirrhosis, rheumatoid arthritis, and multiple sclerosis, to name a few. In such cases, the immune system fails to recognize between foreign agents and its own body cells. Different factors, such as genetic factors (CD25, STAT4), epigenetic factors (DNA methylation, histone modifications) and environmental factors (xenobiotics, drugs, hormones) trigger autoimmunity. Glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), immunosuppressive and biological agents are currently used to manage autoimmune diseases of different origins. However, complete cure remains elusive. Many dietary and natural products including polyphenols have been widely studied as possible alternative treatment strategies for the management of autoimmune disorders. Polyphenols possess a wide-range of pharmacological and therapeutic properties, including antioxidant and anti-inflammatory activities. As immunomodulatory agents, polyphenols are emerging pharmaceutical tools for management of various autoimmune disorders including vitiligo, ulcerative colitis and multiple sclerosis (MS). Polyphenols activate intracellular pathways such as arachidonic acid dependent pathway, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling pathway, mitogen-activated protein kinases (MAPKs) pathway, phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway and epigenetic modulation, which regulate the host's immune response. This timely review discusses putative points of action of polyphenols in autoimmune diseases, characterizing their efficacy and safety as therapeutic agents in managing autoimmune disorders.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Polifenóis/uso terapêutico , Animais , Doenças Autoimunes/imunologia , Humanos , Transdução de Sinais
19.
Autoimmun Rev ; 18(7): 738-748, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059845

RESUMO

CD4+ T helper (Th) cells are a crucial player in host defense but under certain conditions can contribute to the pathogenesis of inflammatory and autoimmune diseases. Beside the Th1/Th2 subset, several additional Th subsets have been identified, each with a distinctive transcription factor, functional properties, signature cytokine profile, and possible role in the pathophysiology of diseases. These newer Th subsets include Th17, regulatory Th cells (Tregs), and more recently, Th9, Th22, and follicular T helper cells. Interestingly, imbalance of Th subsets contributes to the immunopathology of several disease states. Therefore, targeting the imbalance of Th subsets and their signature cytokine profiles by a safe, effective and inexpensive nutraceutical agent such as curcumin could be helpful to treat autoimmune and inflammatory diseases. In this study different Th subsets and how the imbalance of these subsets could promote pathology of several diseases has been reviewed. Furthermore, the role of curcumin in this process will be discussed and the impact of targeting Th subsets by curcumin.


Assuntos
Curcumina/farmacologia , Linfócitos T Auxiliares-Indutores/imunologia , Animais , Doenças Autoimunes/imunologia , Humanos , Hipersensibilidade/imunologia , Doenças Inflamatórias Intestinais/imunologia , Neoplasias/imunologia , Transplante de Órgãos , Psoríase/imunologia
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