Cytokine Polymorphisms, Their Influence and Levels in Brazilian Patients with Pulmonary Tuberculosis during Antituberculosis Treatment

Peresi, Eliana; Oliveira, Larissa Ragozo Cardoso de; Silva, Weber Laurentino da; Costa, Érika Alessandra Pellison Nunes da; Araújo, João Pessoa; Ayres, Jairo Aparecido; Fortes, Maria Rita Parise; Graviss, Edward A.; Pereira, Ana Carla; Calvi, Sueli Aparecida

doi:10.1155/2013/285094

Cited by 19 publications

(23 citation statements)

References 62 publications

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“…In tuberculosis, rs1861494 T allele carriage has been associated with susceptibility as well as a more severe microscopy-positive and bacterial positive form of the disease (18). Furthermore a recent study demonstrated the presence of persistent, elevated levels of IFN-γ in T allele carriers following anti-tuberculosis treatment supporting an association with therapeutic resistance (27). These data suggests a possible mechanistic role in which elevated IFN-γ expression in T allele carriers may lead to a worse prognosis for the resolution of active disease or accelerated progression to complicated and severe disease.…”

Section: Discussionmentioning

confidence: 93%

IFNG rs1861494 Polymorphism Is Associated with IBD Disease Severity and Functional Changes in Both IFNG Methylation and Protein Secretion

Gonsky

Deem

Landers

et al. 2014

Inflammatory Bowel Diseases

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Background Mucosal expression of IFN-γ plays a pivotal role in IBD pathogenesis and IBD-risk regions flank IFNG. The conserved IFNG rs1861494 T/C, introduces a new CpG methylation site, and is associated with disease severity and lack of therapeutic response in other infectious and immune mediated disorders, and is in linkage-disequilibrium with a UC disease severity region. It seems likely that CpG-altering SNPs modify methylation and gene expression. This study evaluated the association between rs1861494 and clinical, serologic and methylation patterns in IBD patients. Methods Peripheral T cells of UC and CD patients were genotyped for rs1861494 and analyzed for allele-specific and IFNG promoter methylation. Serum ANCA and IFN-γ secretion were measured by ELISA and nucleo-protein complex formation by EMSA. Results IFNG rs1861494 T allele carriage in IBD patients was associated with enhanced secretion of IFN-γ. T allele carriage was associated in UC with high levels of ANCA and faster progression to colectomy. In CD, it was associated with complicated disease involving a stricturing/penetrating phenotype. Likewise, IFNG rs1861494 displayed genotype specific modulation of DNA methylation and transcription factor complex formation. Conclusions This study reports the first association of IFNG rs1861494 T allele with enhanced IFN-γ secretion and known IBD clinical parameters indicative of more aggressive disease, as well as serological markers associated with treatment resistance to anti-TNF therapy in IBD patients. These data may be useful prognostically as predictors of early response to anti-TNF therapy to identify IBD patients for improved personalized therapeutics.

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Section: Discussionmentioning

confidence: 93%

IFNG rs1861494 Polymorphism Is Associated with IBD Disease Severity and Functional Changes in Both IFNG Methylation and Protein Secretion

Gonsky

Deem

Landers

et al. 2014

Inflammatory Bowel Diseases

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“…Moreover, genetic regulation is a complex process of multiple genetic sites correlation [16]. Gene polymorphisms and protein products involved in immunologic protective response determine the degree of MTB resistance as well as disease severity and duration [17,18].…”

Section: Introductionmentioning

confidence: 99%

Association of Interleukins Genes Polymorphisms with Multi-Drug Resistant Tuberculosis in Ukrainian Population

Butov

Kuzhko²,

Makeeva

et al. 2016

Advances in Respiratory Medicine

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Introduction: Multi-drug resistant tuberculosis (MDR TB) is a significant health problem in some parts of the world. Three major cytokines involved in TB immunopathogenesis include IL-2, IL-4 and IL-10. The susceptibility to MDR TB may be genetically determined. The aim of the study was to assess the association of IL-2, IL-4, IL-10 gene polymorphisms with multi-drug resistant tuberculosis (MDR TB) in Ukrainian population. Material and methods: We observed 140 patients suffering from infiltrative pulmonary tuberculosis (PT) and 30 apparently healthy subjects. The patients were assigned to two groups whether they suffer or do not suffer from pulmonary MDR TB. Interleukin gene (IL) polymorphisms, particularly T330G polymorphism in the IL-2 gene, C589T polymorphism in the IL-4 gene and G1082A polymorphism in the IL-10 gene were studied through polymerase chain reaction. Circulating levels of IL-2, IL-4 and IL-10 in venous blood were estimated using ELISA. Results: Prior to treatment, patients with PT showed significant increase of IL-2 levels and decrease of IL-4 and IL-10 levels compared to apparently healthy subjects. Circulating IL-4 and IL-10 levels were significantly decreased whilst serum IL-2 level was significantly increased in patients with MDR TB compared to non-MDR TB. Low IL-4 and IL-10 secretion and considerable IL-2 alterations were shown to be significantly associated with mutations of homozygous and heterozygous genotypes affecting C589T polymorphism in the IL-4 gene, G1082A polymorphism in the IL-10 gene and T330G polymorphism in the IL-2 gene in patients with PT. Conclusions: Heterozygous genotype and mutations homozygous genotypes gene in polymorphisms determining specified cytokines’ production is a PT risk factor and may lead to disease progression into chronic phase. Heterozygous genotype of aforementioned cytokine genetic polymorphisms was significantly the most frequent in patients with MDR TB.

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“…Consistently, the increase in actin ring formation, The Mycobacterium tuberculosis is mainly present in macrophages, and causes pathological changes in the body by stimulating the peripheral blood T lymphocytes [27]. Tuberculosis of bone refers to the Mycobacterium tuberculosis invading the bones or joints [28]. If the diagnosis and treatment of bone tuberculosis is not timely, it can cause spinal deformity, limited activity, and even paraplegia, seriously affecting the quality of life of the patients.…”

Section: Discussionmentioning

confidence: 99%

Anti-IFN-γ Antibody Promotes Osteoclastogenesis in Human Bone Marrow Monocyte-Derived Macrophages Co-Cultured with Tuberculosis-Activated Th1 Cells

Deng¹,

Sun²,

Luo³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Tuberculosis induces bone loss and activates Th1 cells that play an important role in the host defense of Bacille Calmette-Guérin tuberculosis vaccine. However, the role of tuberculosis-activated Th1 cells in differentiation of osteoclast precursors to osteoclasts is unclear. As secretion of IFN-γ in Th1 cells is induced by tuberculosis, we aimed to investigate the role of anti-IFN-γ antibody on the differentiation and activation of osteoclasts in bone marrow monocyte-derived macrophages (BMMs). Methods: BMMs were isolated and co-cultured with CD4+T helper 1 cells (Th1 cells), pretreated with anti-IFN-γ antibody. Then, cell proliferation, expression and release of cytokines, formation of actin ring, differentiation of osteoclasts and bone resorption function were measured by CCK8 assay, qRT-PCR/Western blot/flow cytometry, ELISA, immunofluorescence, tartrate-resistant acidic phosphatase (TRAP) staining and bone absorbance assay, respectively. Results: Anti-IFN-γ antibody inhibited the cell viability of BMMs, and induced the expressions of RANKL, TNF-α, NF-κB and TRAF6 in BMMs. In addition, it led to increased expression levels of RANK on cell surfaces, and increased production of RANKL, TNF-α, MCP-1 and SDF-1. Anti-IFN-γ antibody also induced the expression of osteoclast differentiation factor and actin ring formation, but inhibited the expression of osteoprotegerin. TRAP staining and bone resorption assays showed that anti-IFN-γ antibody induced an increase in osteoclast formation and bone resorption. Conclusion: The anti-IFN-γ antibody induced osteoclast formation, and is probably mediated by RANKL-induced activation of NF-κB, that induces TRAF6 in the RANKL-RANK signaling pathway. Our data suggest an inhibitory role for IFN-γ in osteoclast formation induced by tuberculosis.

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Cytokine Polymorphisms, Their Influence and Levels in Brazilian Patients with Pulmonary Tuberculosis during Antituberculosis Treatment

Cited by 19 publications

References 62 publications

IFNG rs1861494 Polymorphism Is Associated with IBD Disease Severity and Functional Changes in Both IFNG Methylation and Protein Secretion

IFNG rs1861494 Polymorphism Is Associated with IBD Disease Severity and Functional Changes in Both IFNG Methylation and Protein Secretion

Association of Interleukins Genes Polymorphisms with Multi-Drug Resistant Tuberculosis in Ukrainian Population

Anti-IFN-γ Antibody Promotes Osteoclastogenesis in Human Bone Marrow Monocyte-Derived Macrophages Co-Cultured with Tuberculosis-Activated Th1 Cells

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