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1.
Scand J Immunol ; 83(1): 52-7, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26368842

ABSTRACT

H. pylori is a potent pathogen due to its capacity to successfully evade host defence mechanisms. Despite inducing immune responses in infected individuals, sometimes these responses fail to clear the infection and the bacterium establishes a persistent infection leading to chronic inflammation. In this context, we hypothesized that human leucocyte antigen G (HLA-G), a non-classical major histocompatibility complex molecule that has the ability to regulate immune responses both in physiological and in pathological conditions, may play an important role in promoting tolerance and helping H. pylori to subvert host defence and consequently establish a chronic infection. Therefore, we evaluated the expression of HLA-G 14-bp Ins/Del polymorphism in patients harbouring H. pylori infection, as well as their relationship with histological and demographic variables, to gain a better understanding of the actual role of HLA-G and its genetic polymorphisms in bacterial infection. Sixty-eight patients with clinical symptoms suggestive of H. pylori infection were enrolled to assess HLA-G 14-bp Ins/Del polymorphism allele and genotype frequencies. After adjustment for covariates (age and gender), the odds of having the genotype Ins/Ins, compared to Del/Del, were 3.77 times greater among HP+ cases than among controls. These findings suggest that the 14-bp Ins/Ins genotype, already associated with inflammatory and autoimmune diseases as well as some viral and parasitic infections, could confer a greater risk of developing H. pylori infection.


Subject(s)
Genetic Predisposition to Disease/genetics , HLA-G Antigens/genetics , Helicobacter Infections/genetics , Adult , Female , Genotype , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide , Reverse Transcriptase Polymerase Chain Reaction , Risk Factors
2.
Scand J Immunol ; 83(1): 38-43, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26346688

ABSTRACT

The subversion mechanisms employed by Helicobacter pylori (H. pylori) to escape from immune surveillance and to establish persistent infection are poorly understood. Growing evidence indicates that expression of HLA-G, a non-classical major histocompatibility complex molecule, negatively regulates immune responses in pathological conditions, including infectious diseases. In this context, we aimed to evaluate HLA-G expression in the gastric microenvironment of individuals harbouring H. pylori and to correlate it with histological variables. Fifty-four gastric specimens from patients harbouring H. pylori infection were evaluated by immunohistochemistry using anti-HLA-G monoclonal antibody. As a result, HLA-G expression was detected in 43 of 54 specimens harbouring H. pylori. The presence of HLA-G was significantly associated with milder colonization by H. pylori (P < 0.02), milder inflammatory activity (P < 0.02) and bacterium histological location in the gastric antrum. This study is the first to explore HLA-G expression in the context of bacterial infection. Whether the biological role of HLA-G during H. pylori infection is beneficial or hazardous for patients remains to be defined.


Subject(s)
Gastric Mucosa/metabolism , HLA-G Antigens/biosynthesis , Helicobacter Infections/metabolism , Gastric Mucosa/immunology , Helicobacter Infections/immunology , Helicobacter pylori , Humans , Immunohistochemistry , Protein Isoforms/biosynthesis , Retrospective Studies , Up-Regulation
3.
Scand J Immunol ; 72(1): 31-7, 2010 Jul.
Article in English | MEDLINE | ID: mdl-20591073

ABSTRACT

The pro-inflammatory cytokines play a critical role in the initiation and propagation of ocular autoimmune diseases. Regulation of these cytokines is generally mediated by the immunoregulatory cytokine such as IL-10 or TGF-beta. In this study, we investigated the immunoregulatory cytokine profile and frequency of natural regulatory T cells (nTregs) in patients with Vogt-Koyanagi-Harada (VKH). We obtained the peripheral blood mononuclear cells (PBMC) from patients with VKH and healthy controls. The cytokine profile from supernatants of PBMC cultured with or without phytohaemagglutinin (PHA) was measured by ELISA, the percentage of CD4(+) Foxp3(+) and CD25(high)Foxp3(+) T regulatory cells were analysed by flow cytometry, and the transcriptional level of Foxp3 expression was analysed by real-time quantitative PCR. The immunoregulatory cytokines, TGF-beta and IL-10, increased in patients with VKH in the inactive stage of the disease. We observed no significant difference in the CD4(+) Foxp3(+) and CD25(high)Foxp3(+) T cells as well as no reduction in FOXP3 mRNA expression in the patients with VKH when compared to healthy controls. We showed in our work, an increase in IFN-gamma secretion by PBMC of patients with VKH in the active stage of the disease when compared to healthy controls and patients in the inactive stage. Our data suggest that IL-10 and TGF-beta cytokines, rather than nTregs are associated with the resolution phase of the disease and may have a more relevant role in controlling this disease.


Subject(s)
Forkhead Transcription Factors/immunology , Interleukin-10/immunology , T-Lymphocytes, Regulatory/immunology , Transforming Growth Factor beta/immunology , Uveomeningoencephalitic Syndrome/immunology , Adult , CD4 Antigens/immunology , Female , Flow Cytometry , Forkhead Transcription Factors/genetics , Humans , Interleukin-2 Receptor alpha Subunit/immunology , Leukocytes, Mononuclear/immunology , Male , Middle Aged , RNA/chemistry , RNA/genetics , Reverse Transcriptase Polymerase Chain Reaction , Young Adult
4.
Clin Immunol ; 132(2): 215-21, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19394278

ABSTRACT

Common Variable Immunodeficiency (CVID) is a primary immunodeficiency disease characterized by defective immunoglobulin production and often associated with autoimmunity. We used flow cytometry to analyze CD4(+)CD25(HIGH)FOXP3(+) T regulatory (Treg) cells and ask whether perturbations in their frequency in peripheral blood could underlie the high incidence of autoimmune disorders in CVID patients. In this study, we report for the first time that CVID patients with autoimmune disease have a significantly reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells in their peripheral blood accompanied by a decreased intensity of FOXP3 expression. Notably, although CVID patients in whom autoimmunity was not diagnosed had a reduced frequency of CD4(+)CD25(HIGH)FOXP3(+) cells, FOXP3 expression levels did not differ from those in healthy controls. In conclusion, these data suggest compromised homeostasis of CD4(+)CD25(HIGH)FOXP3(+) cells in a subset of CVID patients with autoimmunity, and may implicate Treg cells in pathological mechanisms of CVID.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , Common Variable Immunodeficiency/immunology , Forkhead Transcription Factors/immunology , Interleukin-2 Receptor alpha Subunit/immunology , Adolescent , Adult , Aged , Autoimmunity/immunology , CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/cytology , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Common Variable Immunodeficiency/blood , Common Variable Immunodeficiency/genetics , Female , Flow Cytometry , Forkhead Transcription Factors/genetics , Gene Expression , Humans , Lymphocyte Count , Male , Middle Aged , Reverse Transcriptase Polymerase Chain Reaction , T-Lymphocytes, Regulatory/cytology , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Young Adult
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