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2.
Sci Immunol ; 3(24)2018 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-29907691

RESUMO

Heterozygosity for human signal transducer and activator of transcription 3 (STAT3) dominant-negative (DN) mutations underlies an autosomal dominant form of hyper-immunoglobulin E syndrome (HIES). We describe patients with an autosomal recessive form of HIES due to loss-of-function mutations of a previously uncharacterized gene, ZNF341 ZNF341 is a transcription factor that resides in the nucleus, where it binds a specific DNA motif present in various genes, including the STAT3 promoter. The patients' cells have low basal levels of STAT3 mRNA and protein. The autoinduction of STAT3 production, activation, and function by STAT3-activating cytokines is strongly impaired. Like patients with STAT3 DN mutations, ZNF341-deficient patients lack T helper 17 (TH17) cells, have an excess of TH2 cells, and have low memory B cells due to the tight dependence of STAT3 activity on ZNF341 in lymphocytes. Their milder extra-hematopoietic manifestations and stronger inflammatory responses reflect the lower ZNF341 dependence of STAT3 activity in other cell types. Human ZNF341 is essential for the STAT3 transcription-dependent autoinduction and sustained activity of STAT3.

3.
Acta Med Iran ; 55(6): 354-359, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28843235

RESUMO

Inflammatory elements and genetics have major roles in febrile seizures (FS) pathogenesis. Seventy patients were enrolled and compared with 139 controls. The allele and genotype frequency of the IL-2 gene at -330 and +166 positions and the IFN-γ at +874 position were determined. A significant positive association with GG genotype at position -330 in the patient group was found (P=0.003). Further, a positive association was detected in simple and complex FS groups at the same position (P=0.03, P=0.004). IL-2 GT haplotype was significantly more common in the patients compared to controls (P=0.0008). Higher frequency of GT haplotype was detected in simple FS patients in comparison to controls (P=0.0003). Contrary, IL-2 TG haplotype frequency was lower in complex FS group (P=0.005). Overrepresentation of certain alleles, genotypes and haplotypes in IL-2 gene in FS patients could predispose individuals to this disease.


Assuntos
Predisposição Genética para Doença , Interferon gama/genética , Interleucina-2/genética , Convulsões Febris/genética , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Lactente , Masculino , Polimorfismo de Nucleotídeo Único
4.
Acta Microbiol Immunol Hung ; 64(2): 191-201, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28597685

RESUMO

Heterozygous gain-of-function (GOF) mutations in the signal transducer and activator of transcription 1 (STAT1) have increasingly been identified as a genetic cause of autosomal-dominant (AD) chronic mucocutaneous candidiasis (CMC). In this article, we describe a 33-year-old man who experienced chronic refractory candidiasis, recurrent otitis media, and pneumonia resulting in bronchiectasis, severe oral and esophageal candidiases with strictures associated with hypothyroidism and immune hemolytic anemia. His son also suffered from persistent candidiasis, chronic diarrhea, poor weight gain, and pneumonia that resulted in his demise because of sepsis. The immunological workup showed that an inverse CD4/CD8 ratio and serum immunoglobulins were all within normal ranges. The laboratory data revealed failure in response to Candida lymphocyte transformation test. In addition, by Sanger sequencing method, we found a heterozygous mutation, Thr385Met (T385M), located in the DNA-binding domain of STAT1, which was previously shown to be GOF. These findings illustrate the broad and variable clinical phenotype of heterozygous STAT1 GOF mutations. However, more clinical information and phenotype-genotype studies are required to define the clinical phenotype caused by AD STAT1 GOF.


Assuntos
Candidíase Mucocutânea Crônica/genética , Mutação Puntual , Fator de Transcrição STAT1/genética , Adulto , Candida/genética , Candida/isolamento & purificação , Candida/fisiologia , Candidíase Mucocutânea Crônica/microbiologia , Humanos , Masculino , Polimorfismo de Nucleotídeo Único , Transdução de Sinais
6.
Clin Rheumatol ; 36(1): 77-81, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27646136

RESUMO

Juvenile idiopathic arthritis (JIA) is the most common chronic rheumatic disease in children. Genetics and inflammatory elements seem to act as major underlying factors in its pathogenesis. The aim of this study is to identify the associations between interleukin-6 (IL-6) gene polymorphisms and individuals' vulnerability to JIA in a group of Iranian pediatric patients. Fifty-four patients with JIA were enrolled in this investigation and compared with 139 healthy individuals. Using polymerase chain reaction with sequence-specific primers, cytokine genotyping was performed. The allele and genotype frequencies of two single nucleotide polymorphisms (SNPs) within the IL-6 gene at -174 and +565 positions were assessed. A significant positive association was observed for IL -6 -174 G allele in the patient group (p = 0.02). Furthermore, a positive association was observed in patients with JIA for the GG genotype at the same position (p < 0.01), thus revealing a predisposing effect in JIA patients. On the other hand, a significant negative association was found for IL-6 -174 CG genotype (p < 0.01) in the case group. No significant difference was discovered in both the allelic and genotypic frequencies of IL-6 +565 position between patients and controls. Additionally, haplotype analysis divulged over representation of IL-6 GG haplotype in patient group (p < 0.01) as well as IL-6 CG haplotype in healthy controls (p < 0.01). Certain allele, genotype, and haplotype in IL-6 gene were over expressed in patients with JIA, which probably could render individuals more susceptible to this disease.


Assuntos
Artrite Juvenil/genética , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Alelos , Criança , Citocinas/metabolismo , Feminino , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Irã (Geográfico) , Masculino
7.
Clin Rheumatol ; 36(4): 831-836, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27878683

RESUMO

Systemic lupus erythematosus (SLE) is a multi-factor autoimmune disorder with diverse clinical manifestations and unclear pathogenesis. Genetic components play important roles in the incidence and development of SLE. Among these, APRIL as a cytokine has roles in the stimulation and antibody production in B cells. APRIL was hypothesized to be associated with SLE. The aim of this study was to assess the involvement of the APRIL gene in SLE susceptibility in Iranian patients. A single-nucleotide polymorphism (SNP) for rs11552708 of APRIL gene was analyzed by real-time PCR in 60 SLE Iranian children and 64 healthy controls. DNA samples of patients and healthy controls were extracted from peripheral blood leukocytes by phenol-chloroform. Serum samples obtained from 45 children with SLE and 45 healthy controls were assayed by enzyme-linked immunosorbent assay (ELISA). The G/G genotype (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.22-2.07; P = 0.68) and G allele (OR 0.81, 95% CI 0.25-2.56; P = 0.89) frequencies of polymorphism at codon 67 (67G) do not differ significantly in the SLE patients compared with those in the healthy controls. The serum APRIL levels in the SLE patients (mean ± SD = 29.27 ng/ml ± 20.77, range from 0 to 55.33 ng/ml) were significantly higher than those in the healthy controls (P = 0.02). Our results demonstrated that rs11552708 of the APRIL gene is not associated with SLE susceptibility in Iranian children. Likewise, these findings suggest that APRIL antagonist could be a potential therapeutic target to control SLE in children.


Assuntos
Lúpus Eritematoso Sistêmico/sangue , Lúpus Eritematoso Sistêmico/genética , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/sangue , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Adolescente , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Irã (Geográfico) , Masculino , Polimorfismo de Nucleotídeo Único , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
8.
Immunotherapy ; 8(10): 1193-204, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27605068

RESUMO

Epithelial ovarian cancer (EOC) is the most lethal gynecological cancer. Several approaches of active and passive immunotherapy for EOC have been studied. The aim of this systematic review was to assess the clinical efficacy of specific immunotherapy in patients with EOC. We found 4524 references in seven databases and we included ten controlled clinical trials with 2285 patients with EOC reporting five active immunotherapeutic agents and three passive immunotherapies. Meta-analysis of six studies showed that overall there was not any significant difference in overall survival and recurrence-free survival between patients undergoing specific immunotherapy and those in control group. Most of the studies we evaluated reported a positive outcome from treatment with specific immunotherapy, although this was not significant.


Assuntos
Imunoterapia , Neoplasias Epiteliais e Glandulares/terapia , Neoplasias Ovarianas/terapia , Carcinoma Epitelial do Ovário , Ensaios Clínicos como Assunto , Feminino , Humanos , Neoplasias Epiteliais e Glandulares/imunologia , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/mortalidade , Análise de Sobrevida , Resultado do Tratamento
9.
Clin Rheumatol ; 35(8): 1943-1948, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26951255

RESUMO

As cytokines, including interleukin-4 (IL-4), seem to have a pivotal role in the pathogenesis of juvenile idiopathic arthritis (JIA), this study is aimed at investigating of association of polymorphisms in IL-4 and IL-4 receptor α (IL-4RA) genes with susceptibility to JIA. A case-control study was conducted on 53 patients with JIA and 139 healthy unrelated controls. Single nucleotide polymorphisms of IL-4 gene at positions -1098, -590, and -33, as well as IL-4RA gene at position +1902 were genotyped using polymerase chain reaction with sequence-specific primers method and compared between patients and healthy individuals. At the allelic level, C allele at IL-4 -33 was found to be more frequent in patients compared to control (P value <0.01). At the genotypic level, CC genotype at IL-4 -590 (P value <0.01), together with CC and TT genotypes at IL-4 -33 (P value <0.01), were significantly higher in patients with JIA, while TC genotypes at IL-4 -590 and -33 positions were found to be lower in case group (P value <0.01). At the haplotypic level, IL-4 (positions -1098, -509, -33) TTC, GCC, and TTT haplotypes were significantly lower than controls (P value <0.01, P value = 0.03, and P value = 0.04, respectively). Although, TCC haplotype at the same positions was found to be higher in patients (P value <0.01). Polymorphic site of +1902 IL-4RA gene did not differ between cases and controls. Polymorphisms in promoter region of IL-4 but not IL-4RA genes confer susceptibility to JIA and may predispose individuals to adaptive immune responses.


Assuntos
Artrite Juvenil/genética , Subunidade alfa de Receptor de Interleucina-4/genética , Interleucina-4/genética , Polimorfismo de Nucleotídeo Único , Adolescente , Alelos , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Irã (Geográfico) , Masculino
10.
Eur J Med Genet ; 59(4): 237-9, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26808426

RESUMO

ARC syndrome is a rare autosomal recessive disease, characterized by arthrogryposis, renal tubular dysfunction and cholestasis. Herein a 2.5 month old infant with dysmorphic features, including small anterior fontanel, low set ears, beaked nose and high arched palate is presented who was referred because of icterus. He also suffered from some additional anomalies, including unilateral choanal atresia, club foot, and bilateral developmental dislocation of hip, while further studies showed renal tubular acidosis and hearing impairment in addition to cholestasis. Genetic studies showed a homozygous mutation in the VIPAS39 gene. Making the definite diagnosis of the syndrome is important, while increased risk of mutation in other siblings highlights the importance of prenatal diagnosis.


Assuntos
Anormalidades Múltiplas/genética , Acidose Tubular Renal/genética , Artrogripose/genética , Colestase/genética , Insuficiência Renal/genética , Proteínas de Transporte Vesicular/genética , Anormalidades Múltiplas/patologia , Acidose Tubular Renal/patologia , Artrogripose/patologia , Pré-Escolar , Colestase/patologia , Colestase Intra-Hepática/genética , Colestase Intra-Hepática/patologia , Humanos , Masculino , Mutação , Fenótipo , Diagnóstico Pré-Natal , Insuficiência Renal/patologia , Análise de Sequência de DNA , Irmãos
11.
J Child Neurol ; 31(6): 673-7, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26500244

RESUMO

Interleukin-1 (IL-1) plays a key role in inflammation, has an effect on a wide variety of cells, and often leads to tissue destruction. While the ratio between IL-1 and IL-1Ra could influence the development of different diseases of the central nervous system, its gene polymorphisms were investigated in a group of patients with febrile seizures. Ninety patients with febrile seizures were enrolled and compared with 140 controls. The allele and genotype frequency of single nucleotide polymorphisms within the IL-1α, ß, IL-1 R and IL-1Ra gene were determined. The frequency of the IL-1Ra/C allele at position Mspa-I 11100 was decreased significantly (P= .002) and the IL-1Ra/T frequency was significantly increased in patients (P= .002). In addition, the CT genotype frequency at the same position was significantly overrepresented in controls compared to patients (P= .001). Certain alleles and genotypes in the IL-1 gene were overrepresented in patients with febrile seizures, which possibly could predispose individuals to this disease.


Assuntos
Predisposição Genética para Doença/genética , Interleucina-1/genética , Polimorfismo de Nucleotídeo Único/genética , Receptores de Interleucina-1/genética , Convulsões Febris/genética , Criança , Pré-Escolar , Intervalos de Confiança , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Lactente , Masculino , Razão de Chances
12.
J Neurol Sci ; 356(1-2): 153-6, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26119396

RESUMO

Febrile seizures (FS) is the most common seizure disorder during childhood. This study was performed in 78 patients with FS and 137 control subjects to assess polymorphisms of the TNF-α gene at positions -308 and -238, using the polymerase chain reaction and the sequence specific primers method. The highest positive allelic association that made the patients susceptible to FS was seen for TNF-α -238/G (p<0.0001). The GG genotype at TNF-α -238 was significantly higher in the patients with FS, compared to the controls (p=0.0001). Also, GA genotype at the same position was significantly lower in patients than in controls (P=0.0001). The GG haplotype had a significant positive association at TNF-α (308, 238) while GA haplotype showed a negative association (P<0.001). Our data support the idea that TNF-α single-nucleotide polymorphisms play a role in the pathogenesis of FS.


Assuntos
Predisposição Genética para Doença/genética , Polimorfismo de Nucleotídeo Único/genética , Convulsões Febris/genética , Fator de Necrose Tumoral alfa/genética , Pré-Escolar , Feminino , Frequência do Gene , Genótipo , Humanos , Lactente , Masculino
13.
Seizure ; 29: 148-52, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26076859

RESUMO

PURPOSE: Febrile seizures (FS) are the most common convulsive event in children. Inflammatory elements and genetics seem to have major roles in their pathogenesis. METHODS: Seventy nine patients with FS were enrolled in this study and compared with 140 controls. Cytokine genotyping was performed, using polymerase chain reaction with sequence-specific primers. The allele and genotype frequency of three single nucleotide polymorphisms (SNPs) within the IL-10 gene at -1082, -819 and -592 positions (rs1800896, rs1800871, rs1800872), and two SNPs within the TGFB at codons 10 and 25 (rs1982037, rs1800471) were determined. RESULTS: No significant difference was detected in allelic frequency of IL-10 at -1082, -819 and -592 positions (rs1800896, rs1800871, rs1800872) and TGFB at codon 25 (rs1800471), between patients and controls. A significant negative association was observed at the codon 10/CT (rs1982037) in the patient group (OR, 0.5; 95%CI, 0.27-0.93; p=0.026). Further, a negative association was detected in patients with simple FS at same position (OR, 0.41; 95%CI, 0.18-0.93; p=0.03), thus revealing a protective effects in FS patients. There was no significant difference in allelic and genotype frequency between simple and complex FS samples. Furthermore, haplotype analysis revealed significant difference in frequency of TGFB/TC haplotype in comparison between complex FS patients and controls (p=0.048). CONCLUSION: Certain alleles, genotypes, and haplotypes in TGFB genes were over represented in patients with FS, which possibly could predispose individuals to this disease.


Assuntos
Interleucina-10/genética , Polimorfismo de Nucleotídeo Único , Convulsões Febris/genética , Fator de Crescimento Transformador beta1/genética , Criança , Pré-Escolar , Análise Mutacional de DNA , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Lactente , Irã (Geográfico)
14.
Iran J Parasitol ; 10(1): 39-45, 2015 Jan-Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25904944

RESUMO

BACKGROUND: The aim of this study was to detect low parasite and asymptomatic malaria infections by means of three malaria diagnostic tests, in a low transmission region of Minab district, Hormozgan Province, southern Iran. METHODS: Blood samples of 200 healthy volunteers from Bagh-e-Malek area were evaluated using microscopic, rapid diagnostic tests (RDT) and nested-PCR to inspect malaria parasite. RESULTS: The results showed no Plasmodium parasite in subjects by means of microscopy and RDT. However, 3 P. vivax positive samples (1.5%) were discovered by Nested-PCR while microscopy and RDT missed the cases. CONCLUSION: Microscopy as the gold standard method and RDT correctly identified 98.5% of cases, and molecular analysis is sensitive and reliable, especially in the detection of "asymptomatic" infections for active case surveillance. Regarding the existence of asymptomatic malaria in endemic area of Hormozgan, Iran, nested-PCR could be considered as a sensitive tool to interrupt malaria transmission in the country, beside the microscopic and RDT methods.

15.
J Child Neurol ; 30(4): 423-8, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25330798

RESUMO

As of importance of interleukin-4 (IL-4) in inhibiting the production of proinflammatory cytokines, the IL4 gene polymorphisms were investigated in patients with febrile seizure. This association has not been investigated yet, except 1 study which has been done in Japanese population. Eighty-two patients with febrile seizure were enrolled in this study, compared with 139 controls. The allele and genotype frequency of 3 single-nucleotide polymorphisms of IL4 gene were determined. Frequency of the IL4-590/C allele in the patient group was significantly higher than in the control group (P < .0001). Frequency of the following genotypes was significantly lower in patients compared to controls: IL-4 (-590) TC (P = .0001) and IL-4 (-33) TC (P = .001). The most frequent IL-4 haplotype in the patient group was TCC (P = .00) haplotype. In contrast, frequencies of GCC (P = .01), TTT (P = .009), and TTC (P = .0007) haplotypes were significantly lower in febrile seizure patients. Certain alleles, genotypes, and haplotypes in the IL4 gene were overrepresented in Iranian patients with febrile seizure, which could predispose individuals to this disease, and further investigations in other ethnicities are required.


Assuntos
Interleucina-4/genética , Polimorfismo de Nucleotídeo Único , Convulsões Febris/genética , Criança , Pré-Escolar , Frequência do Gene , Técnicas de Genotipagem , Haplótipos , Humanos , Lactente , Irã (Geográfico)
16.
J Neurol Sci ; 342(1-2): 25-8, 2014 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-24834995

RESUMO

Febrile seizures (FSs) are the most common convulsive event in children. Inflammatory elements and genetics have major roles in their pathogenesis. As of the importance of interleukin-6 (IL-6) in FS, this study was performed to assess IL6 single nucleotide polymorphisms (SNPs) in a group of patients with FS. IL6 gene (-174 and +565) SNPs were studied on genomic DNAs of 90 children with FS, using PCR-SSP method. The results were compared to 139 healthy individuals. The presence of the G allele or the GG genotype at +565 position reduced risk of FS, while the A allele at +565 position of the promoter regions was a constituted risk factor for developing FS. This study could support the idea that IL6 SNPs play a role in the pathogenesis of FS.


Assuntos
Interleucina-6/genética , Polimorfismo de Nucleotídeo Único/genética , Convulsões Febris/genética , Alelos , Estudos de Casos e Controles , Pré-Escolar , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Lactente , Masculino , Regiões Promotoras Genéticas/genética
17.
Malar J ; 11: 126, 2012 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-22533733

RESUMO

BACKGROUND: In malaria endemic areas, continuous exposure to Plasmodium parasites leads to asymptomatic carriers that provide a fundamental reservoir of parasites, contributing to the persistence of malaria transmission. Therefore, in the present investigation, the presence and prevalence of malaria asymptomatic cases were determined to evaluate the reservoir of infection in two malaria endemic areas with a previous history of malaria transmission in the south of Iran, Bashagard and Ghale-Ganj districts of Hormozgan and Kerman provinces, respectively, where malaria transmission has been drastically reduced in the recent years. METHODS: The population samples (n = 500 from each of the studied areas) were randomly collected from non-febrile, long-term residing, aged two to over 60 years, during 20092010. Three identical surveys were carried out in both study areas and in each phase all the consent participants were interviewed and clinically examined. In all, three surveys to detect hidden parasite reservoirs (both Plasmodium falciparum and Plasmodium vivax), thick and thin blood smears and a highly sensitive nested-PCR were applied. In addition, the sero-prevalence survey for detecting malaria exposure was done by using a serological marker. RESULTS: In this study, P. vivax and P. falciparum parasites were not detected by light microscopy and nested-PCR assay in all three surveys of samples. Antibody responses against P. vivax and P. falciparum were detected in 1% and 0.2% of the total examined individuals, respectively, in Bashagard district. Regarding to Ghale-Ganj district, about 0.9% of the individuals had IgG -specific antibody to P. vivax at the first and second surveys, but at the third survey 0.45% of the participants had positive antibody to P. vivax parasite. IgG -specific antibody to P. falciparum was detected in 0.2% of the participants at the first and follow-up surveys. The overall regional differences were not statistically significant (P > 0.05). CONCLUSION: Taken together, the lack of asymptomatic carrier with the evidence of extremely low sero-positive to both P. vivax and P. falciparum among examined individuals supported the limited recent transmission in the studied areas and, therefore, these parts of Iran have potential to eliminate the disease in the next few years. However, continued follow up and action are still needed in both studied areas and also in their neighbouring province, Sistan and Baluchistan, which has the highest reported cases of malaria in Iran and also, has the largest border line with Afghanistan and Pakistan, with no elimination activities. This data will provide useful information for managing elimination activities in Iran.


Assuntos
Portador Sadio/epidemiologia , Erradicação de Doenças , Doenças Endêmicas , Malária Falciparum/epidemiologia , Malária Vivax/epidemiologia , Adolescente , Adulto , Doenças Assintomáticas , Sangue/parasitologia , Portador Sadio/parasitologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Malária Falciparum/parasitologia , Malária Vivax/parasitologia , Masculino , Microscopia , Plasmodium falciparum/isolamento & purificação , Plasmodium vivax/isolamento & purificação , Reação em Cadeia da Polimerase , Prevalência , Adulto Jovem
18.
Immunol Invest ; 40(6): 581-96, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21510778

RESUMO

The present study was performed to investigate the effects of dimethylfumarate (DMF) and methylhydrogen fumarate (MHF) on the cytokine pattern of peripheral blood mononuclear cells (PBMCs) of multiple sclerosis (MS) patients. The PBMCs from patients and healthy controls were stimulated with myelin basic protein (MBP) or phytohemagglutinin (PHA) and cultured in the presence of DMF and MHF. The percentage of CD4+IL-4+ and CD4+IFN-γ+ cells was determined by means of intracellular cytokine staining. CD4+IL-4+ cells were significantly increased in the presence of DMF and MHF when PBMCs were stimulated by MBP (P < 0.003). The same significant result was obtained by PHA stimulation (P < 0.049). In terms of CD4+IFN-γ+ cells, the percentage of cells did not significantly differ between the cultures stimulated with MBP or PHA in the presence and absence of the drugs. Results of MBP stimulation in control group also showed a significant increase in CD4+IL-4+ cells in the presence of DMF and MHF. In comparison between patient and control groups, no statistically significant changes were observed. In conclusion, both DMF and MHF effectively increased IL-4 production, whereas they did not significantly change IFN-γ level, indicating the role of these drugs in increasing the production of beneficial cytokines such as IL-4.


Assuntos
Citocinas/metabolismo , Fumaratos/farmacologia , Linfócitos/efeitos dos fármacos , Linfócitos/metabolismo , Esclerose Múltipla/metabolismo , Adolescente , Adulto , Linfócitos T CD4-Positivos/citologia , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Contagem de Células , Sobrevivência Celular/efeitos dos fármacos , Fumarato de Dimetilo , Feminino , Humanos , Interferon gama/metabolismo , Interleucina-4/metabolismo , Leucócitos Mononucleares/citologia , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/imunologia , Leucócitos Mononucleares/metabolismo , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Linfócitos/citologia , Linfócitos/imunologia , Masculino , Maleatos/farmacologia , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Proteína Básica da Mielina/imunologia , Proteína Básica da Mielina/farmacologia , Fito-Hemaglutininas/farmacologia , Células Th1/citologia , Células Th1/efeitos dos fármacos , Células Th1/imunologia , Células Th1/metabolismo , Células Th2/citologia , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Células Th2/metabolismo , Adulto Jovem
19.
Malar J ; 9: 257, 2010 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-20846388

RESUMO

BACKGROUND: The C-terminal region of Plasmodium falciparum merozoite surface protein-1 (PfMSP-1(19)) is a leading malaria vaccine candidate antigen. However, the existence of different variants of this antigen can limit efficacy of the vaccine development based on this protein. Therefore, in this study, the main objective was to define the frequency of PfMSP-1(19) haplotypes in malaria hypoendemic region of Iran and also to analyse cross-reactive and/or variant-specific antibody responses to four PfMSP-1(19) variant forms. METHODS: The PfMSP-1(19) was genotyped in 50 infected subjects with P. falciparum collected during 2006-2008. Four GST-PfMSP-1(19) variants (E/TSR/L, E/TSG/L, E/KNG/F and Q/KNG/L) were produced in Escherichia coli and naturally occurring IgG antibody to these proteins was evaluated in malaria patients' sera (n = 50) using ELISA. To determine the cross-reactivity of antibodies against each PfMSP-1(19) variant in P. falciparum-infected human sera, an antibody depletion assay was performed in eleven corresponding patients' sera. RESULTS: Sequence data of the PfMSP-1(19) revealed five variant forms in which the haplotypes Q/KNG/L and Q/KNG/F were predominant types and the second most frequent haplotype was E/KNG/F. In addition, the prevalence of IgG antibodies to all four PfMSP-1(19) variant forms was equal and high (84%) among the studied patients' sera. Immunodepletion results showed that in Iranian malaria patients, Q/KNG/L variant could induce not only cross-reactive antibody responses to other PfMSP-1(19) variants, but also could induce some specific antibodies that are not able to recognize the E/TSG/L or E/TSR/L variant forms. CONCLUSION: The present findings demonstrated the presence of non-variant specific antibodies to PfMSP-1(19) in Iranian falciparum malaria patients. This data suggests that polymorphism in PfMSP-1(19) is less important and one variant of this antigen, particularly Q/KNG/L, may be sufficient to be included in PfMSP-1(19)-based vaccine.


Assuntos
Anticorpos Antiprotozoários/sangue , Antígenos de Protozoários/imunologia , Malária Falciparum/epidemiologia , Proteína 1 de Superfície de Merozoito/imunologia , Plasmodium falciparum/imunologia , Adolescente , Adulto , Idoso , Antígenos de Protozoários/genética , Criança , Reações Cruzadas , Ensaio de Imunoadsorção Enzimática , Feminino , Genótipo , Humanos , Imunoglobulina G/sangue , Irã (Geográfico)/epidemiologia , Malária Falciparum/transmissão , Masculino , Proteína 1 de Superfície de Merozoito/genética , Pessoa de Meia-Idade , Plasmodium falciparum/genética , Polimorfismo Genético , Adulto Jovem
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