Gene polymorphisms of interleukin-10 and transforming growth factor beta in allergic rhinitis

BACKGROUND: Allergic rhinitis (AR) is a polygenic inflammatory disorder of the upper respiratory airway with an increasing prevalence worldwide. Interleukin-10 (IL-10) and transforming growth factor-beta (TGF-β), as two cytokines with pleiotropic effects on both innate and adaptive immunity, play important roles in allergic responses. Therefore, this study was performed to evaluate the associations of five polymorphisms of IL-10 and TGF-β genes with AR. MATERIALS AND METHODS: Ninety-eight patients with AR along with 140 healthy volunteers with no history of AR and with the same ethnicity of the patients were recruited in this study. Genotyping was done for three polymorphisms in promoter region of IL-10 gene (rs1800896, rs1800871, rs1800872), and two polymorphisms in the exonic region of TGF-β1 gene (rs1982037, rs1800471) using PCR sequence-specific-primers method. RESULTS: A allele and AA genotype in rs1800896 of IL-10 and TT genotype in rs1982037 in TGF-β were significantly less frequent in the patients than in controls. While the C allele and the CG genotype in rs1800471 in TGF-β1 were associated with a higher susceptibility to AR. C/C and T/C haplotypes (rs1982037, rs1800471) in TGF-β1 gene and A/C/A, A/T/C and G/C/A haplotypes (rs1800896, rs1800871, rs1800872) in IL-10 gene were found with higher frequencies in patients than controls. Patients with CC genotype in rs1800871 in Il-10 had significantly lower levels of IgE. CONCLUSION: We found that certain genetic variants in IL-10 and TGF-β polymorphisms were associated with susceptibility to AR as well as some clinical parameters in the patients with AR

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Gene polymorphisms of interleukin-10 and transforming growth factor beta in allergic rhinitis.

BACKGROUND: Allergic rhinitis (AR) is a polygenic inflammatory disorder of the upper respiratory airway with an increasing prevalence worldwide. Interleukin-10 (IL-10) and transforming growth factor-beta (TGF-ß), as two cytokines with pleiotropic effects on both innate and adaptive immunity, play important roles in allergic responses. Therefore, this study was performed to evaluate the associations of five polymorphisms of IL-10 and TGF-ß genes with AR. MATERIALS AND METHODS: Ninety-eight patients with AR along with 140 healthy volunteers with no history of AR and with the same ethnicity of the patients were recruited in this study. Genotyping was done for three polymorphisms in promoter region of IL-10 gene (rs1800896, rs1800871, rs1800872), and two polymorphisms in the exonic region of TGF-ß1 gene (rs1982037, rs1800471) using PCR sequence-specific-primers method. RESULTS: A allele and AA genotype in rs1800896 of IL-10 and TT genotype in rs1982037 in TGF-ß were significantly less frequent in the patients than in controls. While the C allele and the CG genotype in rs1800471 in TGF-ß1 were associated with a higher susceptibility to AR. C/C and T/C haplotypes (rs1982037, rs1800471) in TGF-ß1 gene and A/C/A, A/T/C and G/C/A haplotypes (rs1800896, rs1800871, rs1800872) in IL-10 gene were found with higher frequencies in patients than controls. Patients with CC genotype in rs1800871 in Il-10 had significantly lower levels of IgE. CONCLUSION: We found that certain genetic variants in IL-10 and TGF-ß polymorphisms were associated with susceptibility to AR as well as some clinical parameters in the patients with AR.

Mortality and morbidity in patients with X-linked agammaglobulinaemia

BACKGROUND: X-linked agammaglobulinaemia (XLA) is a genetic disorder characterised by a defect in the generation of mature B cells, lack of antibodies production, and susceptibility to recurrent bacterial infections. Understanding of the risk factors responsible for morbidity and mortality in these patients can help in a better management of this disorder. However, there is a lack of specific studies in the literature regarding the morbidity and mortality of XLA patients. This study is designed to evaluate morbidities and mortality and survival rates in Iranian patients with XLA diagnosis during the past 20 years. METHODS: We have registered the clinical data of the XLA patients and followed them up until 2010. At the time of diagnosis, a four-page questionnaire including complete medical information was filled out for all patients. Follow-up information was gathered either by reviewing the patients' hospital records or regularly visiting the patients. RESULTS: Among 41 patients, 26.8% died during the follow up period. All of the complications before the initiation of treatment such as pneumonia, otitis media and diarrhoea were reduced after immunoglobulin replacement, except sinusitis and conjunctivitis. There were significant associations between some immunological and clinical characteristics such as lymphocyte subsets, consanguinity marriage and mortality. CONCLUSION: Despite recent advances in the treatment of XLA, these patients still suffer from severe complications. Associations between poor prognosis and clinical and some immunological characteristics of the patients may help physicians to select poor prognoses patients at higher risk of mortality to develop prevention strategies for them

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Mortality and morbidity in patients with X-linked agammaglobulinaemia.

BACKGROUND: X-linked agammaglobulinaemia (XLA) is a genetic disorder characterised by a defect in the generation of mature B cells, lack of antibodies production, and susceptibility to recurrent bacterial infections. Understanding of the risk factors responsible for morbidity and mortality in these patients can help in a better management of this disorder. However, there is a lack of specific studies in the literature regarding the morbidity and mortality of XLA patients. This study is designed to evaluate morbidities and mortality and survival rates in Iranian patients with XLA diagnosis during the past 20 years. METHODS: We have registered the clinical data of the XLA patients and followed them up until 2010. At the time of diagnosis, a four-page questionnaire including complete medical information was filled out for all patients. Follow-up information was gathered either by reviewing the patients' hospital records or regularly visiting the patients. RESULTS: Among 41 patients, 26.8% died during the follow up period. All of the complications before the initiation of treatment such as pneumonia, otitis media and diarrhoea were reduced after immunoglobulin replacement, except sinusitis and conjunctivitis. There were significant associations between some immunological and clinical characteristics such as lymphocyte subsets, consanguinity marriage and mortality. CONCLUSION: Despite recent advances in the treatment of XLA, these patients still suffer from severe complications. Associations between poor prognosis and clinical and some immunological characteristics of the patients may help physicians to select poor prognoses patients at higher risk of mortality to develop prevention strategies for them.

RAD50 single-nucleotide polymorphism in predominantly antibody deficiency

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AICDA single nucleotide polymorphism in common variable immunodeficiency and selective IgA deficiency

BACKGROUND: Primary antibody deficiencies (PADs) are a heterogeneous group of disorders, characterised by increased susceptibility to recurrent bacterial infections. Common variable immunodeficiency (CVID) is the most important PAD from the clinical point of view and selective IgA deficiency (IgAD) is the most common PAD. However, the underlying gene defect in both is still unknown. As a recent study in Europe showed an association between a single nucleotide polymorphism (SNP) of AICDA gene with PADs, this study was performed to evaluate such an association in Iranian patients. METHODS: Fifty-eight patients with PAD, including 39 CVID and 19 IgAD, as well as 34 healthy volunteers, were enrolled in this study. Genotyping was done in all groups for an intronic SNP in AICDA (rs2580874), using real-time PCR genotyping assay. RESULTS: The less frequent genotype of AICDA in IgAD patients was AA, seen in 10.5% of the patients, which was much lower than the 30.8% in CVID patients and 38.2% in the controls. However, these differences were not significant. Indeed the GG genotype in the patients with PADs was seen in 20.7%, compared to 8.8% in the controls without any significant difference. CONCLUSIONS: There was no significant association between the previously reported genetic variant of AICDA gene and the development of CVID or IgAD, but further multi-center studies are also needed

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AICDA single nucleotide polymorphism in common variable immunodeficiency and selective IgA deficiency.

BACKGROUND: Primary antibody deficiencies (PADs) are a heterogeneous group of disorders, characterised by increased susceptibility to recurrent bacterial infections. Common variable immunodeficiency (CVID) is the most important PAD from the clinical point of view and selective IgA deficiency (IgAD) is the most common PAD. However, the underlying gene defect in both is still unknown. As a recent study in Europe showed an association between a single nucleotide polymorphism (SNP) of AICDA gene with PADs, this study was performed to evaluate such an association in Iranian patients. METHODS: Fifty-eight patients with PAD, including 39 CVID and 19 IgAD, as well as 34 healthy volunteers, were enrolled in this study. Genotyping was done in all groups for an intronic SNP in AICDA (rs2580874), using real-time PCR genotyping assay. RESULTS: The less frequent genotype of AICDA in IgAD patients was AA, seen in 10.5% of the patients, which was much lower than the 30.8% in CVID patients and 38.2% in the controls. However, these differences were not significant. Indeed the GG genotype in the patients with PADs was seen in 20.7%, compared to 8.8% in the controls without any significant difference. CONCLUSIONS: There was no significant association between the previously reported genetic variant of AICDA gene and the development of CVID or IgAD, but further multi-center studies are also needed.

Autoimmune phenotype in patients with common variable immunodeficiency.

BACKGROUND AND OBJECTIVE: Autoimmune disorders occur with a higher incidence in common variable immunodeficiency (CVID) patients than in the general population. To describe the clinical features of the autoimmune phenotype in patients with CVID. METHODS: The hospital records of all diagnosed CVID patients referred to the Children's Medical Center Hospital in Tehran, Iran between 2000 and 2010 were reviewed. Patients were also classified according to the presence or absence of autoimmune disease. RESULTS: Of 52 patients studied, 26.9% (n=14) had shown at least 1 autoimmune manifestation during the study period. Autoimmune cytopenias and juvenile rheumatoid arthritis were the most common form of autoimmunity in our series. Autoimmunity was significantly associated with polyclonal lymphocytic infiltrative disorders (P = .017), increased serum Immunoglobulin (Ig) M levels (P < .001), decreased IgE values (P = .04) and diminished switched memory B-cell count (P < .001). CONCLUSIONS: Because autoimmunity is one of the first manifestations in CVID, humoral immune system tests should be considered in autoimmune patients with a history of recurrent infection. The presence of polyclonal lymphocytic infiltrative disorders and decreased switched memory B-cells may predispose CVID patients to autoimmunity.

Single-Nucleotide Polymorphisms of TNFA and IL1 in Allergic Rhinitis

Background: Allergic rhinitis is a complex polygenic disorder of the upper respiratory tract. Given that proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin (IL) 1 seem to play a role in the development of allergic rhinitis, we evaluated the associations between various single-nucleotide polymorphisms (SNPs) of the TNF and IL1 genes in a case-control study. Methods: The study population comprised 98 patients with allergic rhinitis. Genotyping was performed using polymerase chain reaction with sequence-specific primers for 2 TNFA promoter variants (rs1800629 and rs361525), 1 variant in the promoter region of IL1A (rs1800587), 2 SNPs in the IL1B gene (rs16944 and rs1143634), 1 variant in the IL1 receptor (rs2234650), and 1 in IL1RA (rs315952). Results: Patients who were homozygous for the T allele of rs16944 in IL1B had an 8.1-fold greater risk of allergic rhinitis than those with the C allele. In TNFA, a significant relationship was also detected between rs1800629 and rs361525 and allergic rhinitis. Except for rs1800587 in IL1A and rs315952 in IL1RA, significant differences were found between the patient and control groups for all other SNPs. Conclusions: We found that allelic variants in the TNFA and IL1 genes were not only associated with the risk of developing allergic rhinitis, but also affected disease course and severity (AU)

Antecedentes: La rinitis alérgica es una alteración poligénica compleja de las vías respiratorias. El TNF y la familia de la IL-1, como citoquinas proinflamatorias, parecen jugar un papel en el desarrollo de la rinitis alérgica. En este estudio de casos y controles, se evalúan las posibles asociaciones de diferentes polimorfismos de nucleótidos simples (SNPs) de los genes que regulan TNF- α e IL1. Métodos: Se estudiaron 19 pacientes con rinitis alérgica, los cuales fueron genotipados mediante PCR para primeras especie-específicos, para dos variantes del promotor del TNF- α (rs1800629 y rs361525), uno en el receptor de IL1 (rs2234650), dos SNPs en el gen de IL1ß (rs16944 y rs1143634), uno en el receptor de IL1 receptor (rs2234650) y IL1RA (rs315952). Resultados: En cuanto a los resultados obtenidos, los pacientes homicigotos para el alelo T de rs16944 en IL1ß mostraron un riesgo 8.1 veces mayor de tener rinitis alérgica que los que presentaban el alelo C. Con respecto al TNF- α, se observó una relación significativa entre los dos SNPs rs1800629 y rs361525 con la presentación de una rinitis alérgica. Excepto rs1800587, en IL1 α, y rs315952 en IL1RA, encuentran una diferencia significativa entre el grupo control y el de pacientes para el resto de los SNPs. Algunos SNPs se asociaron con el curso y con la gravedad de la enfermedad. Conclusiones: En conclusión, encontramos variantes genéticas de TNF-α y IL1 que se asocian con el riesgo de desarrollar una rinitis alérgica, y que también afectan al curso y gravedad de la enfermedad (AU)

Autoimmune Phenotype in Patients With Common Variable Immunodeficiency

Antecedentes y objetivo: Las enfermedades autoinmunes se presentan asociadas, con una alta incidencia, en los pacientes con inmunodeficiencia común variable (IDCV), respecto a la población normal. El objetivo de este estudio fue describir los hechos clínicos del fenotipo autoinmune en pacientes con IDCV. Métodos: Se revisaron las historias clínicas de todos los pacientes diagnosticados de IDCV del Medical Center Hospital de Teherán en el periodo de 2000-2010. Los pacientes fueron clasificados en dos grupos: con y sin enfermedades autoinmunes asociadas. Resultados: De los 52 pacientes estudiados, un 26.9% (14 pacientes) habían mostrado al menos una manifestación de enfermedad autoinmune durante el tiempo del estudio. Las citopenias autoinmunes y la artritis reumatoide juvenil fueron las manifestaciones más frecuentes en nuestra serie. Encontramos en nuestros pacientes asociaciones significativas entre enfermedades infiltrativas polilinfocíticas (p=0.017), incremento de niveles de IgM sérica (p<0.001) y disminución de cifras de IgE (p=0.04) con desarrollo de autoinmunidad, así como una disminución de las células B memoria (p<0.001). Conclusión: La autoinmunidad puede considerarse una de las manifestaciones iniciales en los pacientes con IDCV, por lo que se aconseja explorar el sistema inmunológico humoral mediante test in vitro, en aquellos pacientes con historias de infecciones de repetición. Por otra parte la presencia de enfermedades infiltrativas polilinfocíticas y la disminución de las células B memoria en pacientes con IDCV, pueden predisponer al desarrollo de una enfermedad autoinmune (AU)

Background and objective: Autoimmune disorders occur with a higher incidence in common variable immunodeficiency (CVID) patients than in the general population. To describe the clinical features of the autoimmune phenotype in patients with CVID. Methods: The hospital records of all diagnosed CVID patients referred to the Children’s Medical Center Hospital in Tehran, Iran between 2000 and 2010 were reviewed. Patients were also classified according to the presence or absence of autoimmune disease. Results: Of 52 patients studied, 26.9% (n=14) had shown at least 1 autoimmune manifestation during the study period. Autoimmune cytopenias and juvenile rheumatoid arthritis were the most common form of autoimmunity in our series. Autoimmunity was significantly associated with polyclonal lymphocytic infiltrative disorders (P=.017), increased serum Immunoglobulin (Ig) M levels (P<.001), decreased IgE values (P=.04) and diminished switched memory B-cell count (P<.001). Conclusions: Because autoimmunity is one of the first manifestations in CVID, humoral immune system tests should be considered in autoimmune patients with a history of recurrent infection. The presence of polyclonal lymphocytic infiltrative disorders and decreased switched memory B-cells may predispose CVID patients to autoimmunity (AU)

Single-nucleotide polymorphisms of TNFA and IL1 in allergic rhinitis.

BACKGROUND: Allergic rhinitis is a complex polygenic disorder of the upper respiratory tract. Given that proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin (IL) 1 seem to play a role in the development of allergic rhinitis, we evaluated the associations between various single-nucleotide polymorphisms (SNPs) of the TNF and IL1 genes in a case-control study. METHODS: The study population comprised 98 patients with allergic rhinitis. Genotyping was performed using polymerase chain reaction with sequence-specific primers for 2 TNFA promoter variants (rs1800629 and rs361525), 1 variant in the promoter region of IL1A (rs1800587), 2 SNPs in the IL1B gene (rs16944 and rs1 143634), 1 variant in the IL1 receptor (rs2234650), and 1 in IL1RA (rs315952). RESULTS: Patients who were homozygous for the T allele of rs16944 in IL1B had an 8.1-fold greater risk of allergic rhinitis than those with the C allele. In TNFA, a significant relationship was also detected between rs1800629 and rs361525 and allergic rhinitis. Except for rs1800587 in IL1A and rs315952 in IL1RA, significant differences were found between the patient and control groups for all other SNPs. CONCLUSIONS: We found that allelic variants in the TNFA and IL1 genes were not only associated with the risk of developing allergic rhinitis, but also affected disease course and severity.