RESUMEN
Th17 cells contribute the pathobiology of autoimmune diseases, including rheumatoid arthritis (RA). However, it was shown that differentiated Th17 cells display a high degree of plasticity under the influence of inflammatory conditions. In some autoimmune diseases, the majority of Th17 cells, especially at sites of inflammation, have a phenotype that is intermediate between Th17 and Th1. These cells, which are described as Th17.1 or exTh17 cells, are hypothesized to be more pathogenic than classical Th17 cells. In this review, the involvement of Th17.1 lymphocytes in RA, and potential features that might render these cells to be more pathogenic are discussed.
Asunto(s)
Microbioma Gastrointestinal/efectos de los fármacos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Esclerosis Múltiple/dietoterapia , Remielinización/efectos de los fármacos , Simvastatina/uso terapéutico , Microbioma Gastrointestinal/fisiología , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/farmacología , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/metabolismo , Remielinización/fisiología , Simvastatina/farmacologíaRESUMEN
Multiple sclerosis (MS) is an autoimmune disorder in which the immunopathogenesis is not fully understood. In the recent years, the role of gut microbiome in the pathogenesis of this disorder has been highlighted. Bifidobacteria as a component of gut microbiome might also be involved in MS pathogenesis. Being emerged in early days after birth, bifidobacteria have a prominent role in immune system maturation and function. Some factors like mode of delivery, breast feeding, mother's blood group and her secretory state and also environmental factors could influence its level in the early infancy, which may remain throughout lifetime. In this review, we discussed possible immunopathogenic link between the bifidobacteria and MS.
Asunto(s)
Bifidobacterium , Microbioma Gastrointestinal , Esclerosis Múltiple , Bifidobacterium/fisiología , Microbioma Gastrointestinal/inmunología , Humanos , Esclerosis Múltiple/etiología , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/microbiologíaRESUMEN
Multiple sclerosis (MS) is a chronic inflammatory disorder with several genetic and environmental factors being implicated in its pathogenesis. Protein prenylation as one of the important posttranslational modifications of proteins has crucial role in immune system regulation. In the current case-control study, we compared expression of five genes coding for the different subunits of proteins implicated in protein prenylation in 50 Iranian MS patients with those of healthy subjects. No significant difference has been found in FNTA and PGGT1B expressions between cases and controls. Spearman correlation analysis between FNTA relative expression and disease duration showed significant correlation in male patients (r = - 0.671, P = 0.024) but not female patients (r = 0.253, P = 0.12). FNTB expression was significantly higher in MS patients compared with healthy subjects. Spearman correlation analysis between FNTB relative expression and disease duration showed significant correlation in male patients (r = -0.876, P = 0.004) but not female patients (r = 0.296, P = 0.06). RABGGTA was significantly upregulated in total MS patients, total male patients, female patients aged between 30 and 40 and male patients aged >40 compared with corresponding control groups. RABGGTB was significantly downregulated in total MS patients, total female patients, and female patients aged > 40 compared with corresponding control groups. Totally, we demonstrated dysregulation of protein prenylation pathway in MS patients compared with healthy subjects. Future studies are needed to find the clinical implication of this pathway in MS patients.
Asunto(s)
Esclerosis Múltiple/metabolismo , Prenilación de Proteína , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adulto , Transferasas Alquil y Aril/genética , Transferasas Alquil y Aril/metabolismo , Estudios de Casos y Controles , Farnesiltransferasa/genética , Farnesiltransferasa/metabolismo , Femenino , Humanos , MasculinoRESUMEN
Vascular endothelial growth factor (VEGF) and its receptor kinase insert domain-containing receptor (KDR) pathway trigger the process of angiogenesis as well as inflammation, which contributes to the development and progression of demyelinating lesions in multiple sclerosis. This work is a case-control study comprising of a total of 400 subjects with multiple sclerosis and 400 healthy controls. Participants were subjected to neurological examination and peripheral blood sampling for genotyping. Polymorphisms in the VEGF and KDR genes were assessed using the restriction fragment length polymorphism (RFLP-PCR) method. A significantly higher frequency of the T allele and TT genotype of the VEGF 936C > T (rs3025039) polymorphism was found in the multiple sclerosis group than in the healthy control group (P = 0.01 [OR = 1.41] and P = 0.01 [OR = 3.12], respectively). In addition, VEGF 936C > T showed an association with patients in a recessive model. However, the KDR -604T > C (rs2071559) polymorphism showed no significant difference in either allelic or genotype frequency between the two groups. Taken together, the results of the present study suggests that the T allele of the rs3025039 in VEGF gene could be considered a risk factor for developing multiple sclerosis in the Iranian population.
Asunto(s)
Esclerosis Múltiple/genética , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido Simple , Factor A de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Irán , MasculinoRESUMEN
Ras-like without CAAX2 (RIT2) which encodes a GTP-binding protein has recently been reported as a new susceptibility gene for Autism Spectrum Disorders (ASD) in a genome-wide association study. Since the gene is suggested to be involved in the pathogenesis of different neurological diseases, we investigated the association of two single nucleotide polymorphisms (SNP) rs16976358 and rs4130047 of this gene with ASD in Iranian patients. A total of 1004 individuals, comprising 532 ASD cases and 472 healthy subjects participated in this study. Allele frequency analyses showed significant over-presentation of rs16976358-C allele in cases versus controls (P < 0.0001). In addition, rs16976358 CC genotype (OR (95% CI) =3.57(1.72-7.69) and P < 0.0001) and rs4130047 CC genotype (OR (95% CI) =0.64(0.43-0.97) and P = 0.035) were associated with ASD in recessive inheritance model. Besides, haplotype analysis demonstrated an association between the C/T haplotype block (rs16976358/rs4130047) and ASD (OR (95%CI) = 0.44 (0.31-0.62), P < 0.0001). Altogether, our findings provided additional confirmation for the RIT2 gene participation in ASD risk and suggested the rs16976358 variant as a possible genetic risk factor for this disorder.
Asunto(s)
Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/genética , Predisposición Genética a la Enfermedad/genética , Proteínas de Unión al GTP Monoméricas/genética , Polimorfismo de Nucleótido Simple/genética , Adolescente , Trastorno del Espectro Autista/epidemiología , Estudios de Casos y Controles , Niño , Femenino , Predisposición Genética a la Enfermedad/epidemiología , Variación Genética/genética , Humanos , Irán/epidemiología , MasculinoRESUMEN
Multiple sclerosis (MS) is a chronic autoimmune disease, and the most common cause of nontraumatic disability in young people. The etiology of this disease is not well defined yet. Cytokines play an important role in differentiation, maturation and survival of a wide range of cells, including cells of the immune system. Suppressor of cytokine signaling (SOCS) proteins are the most important regulators of this cytokine signaling pathway. The aim of present study was to compare the expression levels of SOCS1, SOCS2, SOCS3 and SOCS5 genes in the blood of 50 relapsing-remitting MS (RR-MS) patients and 50 healthy controls by Taqman Quantitative Real-Time PCR in patients and healthy control group. We observed that SOCS1 and SOCS5 expression was significantly down-regulated (P=0.045 and P=0.044, respectively); whereas, no significant difference was observed between MS patients and controls for SOCS2 and SOCS3 gene expression (P=0.747 and P=0.439, respectively). In addition, there was no significant correlation between the expression of SOCS1, SOCS2, SOCS3 and SOCS5 genes and clinical findings, such as the level of physical disability in the MS patients according to the Kurtzke Expanded Disability Status Scale (EDSS) criterion and disease duration. However, a significant positive correlation was observed between expression levels of SOCS genes. This study shows that loss of balance among various members of the SOCS family proteins may contribute to pathophysiology of multiple sclerosis.
Asunto(s)
Salud de la Familia , Esclerosis Múltiple/sangre , Esclerosis Múltiple/genética , Transducción de Señal/genética , Proteínas Supresoras de la Señalización de Citocinas/sangre , Proteínas Supresoras de la Señalización de Citocinas/genética , Adolescente , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Modelos Moleculares , ARN Mensajero/metabolismo , Estadística como Asunto , Transcriptoma , Adulto JovenRESUMEN
Retinoic acid receptor-related orphan receptor alpha (RORA) is proposed to promote Th17 cells differentiation that play a crucial role in many inflammatory diseases, including multiple sclerosis (MS). The gene is also involved in regulation of inflammatory responses and neuronal cell development. The aim of the present study is to determine if any relation exists between RORA rs11639084 and rs4774388 gene polymorphisms on the individual susceptibility of multiple sclerosis. 410 patients with clinically definite MS and 500 ethnically-matched healthy controls participated in this study. Genotyping was performed using tetra primer-amplification refractory mutation system-PCR (4P-ARMS-PCR) method for the mentioned polymorphisms in the RORA gene. Both variants showed significant differences in allele and genotype distributions between the studied groups. Genotypes were risk associated in additive (P-value of 0.0003 and odds ratio equal to 1.7 (95% CI: 1.27-2.26)), dominant (P-value of <0.0001 and odds ratio equal to 0.55 (95% CI: 0.41-0.73)) and recessive (P-value of 0.04 and odds ratio equal to 0.33 (95% CI: (0.12-0.96)) models for rs11639084. However, the rs4774388 genotypes were risk associated in recessive model with a P-value of 0.036 and an odds ratio of 0.62 (95% CI: (0.4-0.97)). To the best of our knowledge this is the first report concerning the association between RORΑ gene polymorphisms and MS. The further study of RORΑ related pathways and gene networks might result in the better understanding of the pathophysiology of MS and related symptoms.