Paria Heydarinezhad; Nasser Gholijani; Zahra Habibagahi; Mohammad Reza Malekmakan; Zahra Amirghofran
Abstract
Background: FOXP3, an important transcription factor of regulatory T cells has shown a contribution to the development of various autoimmune diseases. Objectives: To investigate the influence of FOXP3 polymorphisms (rs3761548 and rs2294021) on systemic lupus erythematosus (SLE) susceptibility and patients' ...
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Background: FOXP3, an important transcription factor of regulatory T cells has shown a contribution to the development of various autoimmune diseases. Objectives: To investigate the influence of FOXP3 polymorphisms (rs3761548 and rs2294021) on systemic lupus erythematosus (SLE) susceptibility and patients' characteristics. Methods: Genotyping was performed on 265 patients with SLE and 404 healthy controls using PCR-RFLP. Patients' demographic, laboratory, and clinical information were all documented. The relationship between the SNPs and patients' characteristics was statistically analyzed. Results: The frequency of C/- genotype in male patients was significantly higher than in the healthy male controls, whereas the frequency of A/- genotype was lower (OR=0.53; 95% CI=0.28-1.00, p=.05). Analysis of the correlation between these SNPs and the patients' characteristics showed a longer disease duration in the rs3761548 C/- carriers and a correlation with arthralgia in both SNPs. In the females, there was a significant association between CC haplotype and disease susceptibility (OR=0.6, CI=0.38-0.94, p=.027). A significant association of both SNPs with the history of abortion was also detected. The frequencies of the rs3761548 AA (p=.006) and the rs2294021 CC genotypes (p=.038) and AC/AC combination (p=.033) were higher in women who had an abortion. We found a correlation between the rs3761548 AC genotype and the decreased C4 level and cardiovascular involvement, and the rs2294021 CC genotype with ESR, neurological involvement, and photosensitivity. Conclusions: FOXP3 rs3761548 C/- genotype association with disease susceptibility in male patients, an association of both SNPs with the abortion risk in female patients, and the correlation between these SNPs and several clinical features of the patients suggest their association with the disease development and pathology.
Mohammadreza Yazdani; Shahdad Khosropanah; Ahmad Hosseini; Mehrnoosh Doroudchi
Volume 13, Issue 4 , December 2016, , Pages 249-262
Abstract
Background: Atherosclerosis is a chronic inflammatory disease affecting large and
medium arteries. CD4+ T cells are known to play a role in the progression of the
disease. CD4+CD25+Foxp3+ natural Treg (nTreg) cells seem to have a protective role
in the disease and their reduction in acute coronary ...
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Background: Atherosclerosis is a chronic inflammatory disease affecting large and
medium arteries. CD4+ T cells are known to play a role in the progression of the
disease. CD4+CD25+Foxp3+ natural Treg (nTreg) cells seem to have a protective role
in the disease and their reduction in acute coronary syndrome is recently shown.
Objective: To investigate the frequency of nTreg subsets in the peripheral blood of
patients with atherosclerosis. Methods: Confirmation of atherosclerosis was done by
angiography and 15 ml heparinized blood was obtained from each of the 13 nondiabetic
patients and 13 non-diabetic, non-smoker individuals with normal/insignificant
coronary artery disease which was also confirmed by angiography. Lipid profiles of the
patients and controls were measured at the time of sampling. Mononuclear cells were
used for both RNA extraction and immunophenotyping by real-time PCR and
flowcytometry techniques, respectively. Results: In natural Treg subsets, the frequency
of CD4+CD45RO-CD25+Foxp3lo T-cells (resting nTregs) was greater in controls than
patients (p=0.02). The frequency of CD4+CD45RO+CD25hiFoxp3hi T-cells (activated
nTregs) was significantly higher in controls compared with patients (p=0.02). However,
the frequency of CD4+CD25+CD45RO+Foxp3- T-cells (effector/memory) increased in
patients compared with controls (p=0.01). Both the MFI and gene expression of Foxp3
were higher in control group than in patients (p=0.015 and p=0.017, respectively).
Moreover, the TGF-β gene expression showed a decrease in the peripheral blood
mononuclear cells of patients compared with controls (p=0.03). Conclusion: Decrease
in both subsets of resting and activated nTregs along with a decrease in the expression
of Foxp3 and TGF-β genes in patients with atherosclerosis suggests phenotypic changes
in these subsets, which may as well be correlated with a more inflammatory profile in
their lymphocytes.
Maryam Hamidinia; Mehri Ghafourian Boroujernia; Abdolhassan Talaiezadeh; Ghasem Solgi; Maryam Taghdiri; Ali Khodadadi
Volume 10, Issue 1 , March 2013, , Pages 22-30
Abstract
Background: Regulatory T cells (T-regs) have an important role in cancer by suppression of protective antitumor immune responses. Regulatory T cells express the forkhead/winged helix transcription factor (FOXP3) and OX40 molecules which have important regulatory roles in the immune system. Objective: ...
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Background: Regulatory T cells (T-regs) have an important role in cancer by suppression of protective antitumor immune responses. Regulatory T cells express the forkhead/winged helix transcription factor (FOXP3) and OX40 molecules which have important regulatory roles in the immune system. Objective: To evaluate FOXP3 and OX40 transcripts in the peripheral blood mononuclear cells of women with breast cancer. Methods: Blood samples from 40 women with histologically-confirmed infiltrating ductal carcinoma of the breast and 40 healthy volunteer women without a history of malignancy or autoimmune disorders were collected. The abundance of FOXP3 and OX40 gene transcripts were determined by quantitative real-time PCR (qRT-PCR). Results: There was a significant positive correlation between FOXP3 and OX40 gene expression in women with breast cancer in a stage dependent manner. Conclusion: This finding emphasizes the importance of T-regs as predominant targets for breast cancer immunotherapy.
Haddi Hassannia; Saeid Abediankenari; Javad Ghaffari
Volume 8, Issue 4 , December 2011, , Pages 218-225
Abstract
Background: Regulatory CD4+T (Treg) cells are effective in maintaining immune tolerance. Objective: To investigate single nucleotide polymorphisms (SNPs) of Transforming Growth Factor β-1 (TGF-β1) and Forkhead Box Protein 3 (FOXP3) genes in Iranian patients with allergic rhinitis (AR). Methods: ...
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Background: Regulatory CD4+T (Treg) cells are effective in maintaining immune tolerance. Objective: To investigate single nucleotide polymorphisms (SNPs) of Transforming Growth Factor β-1 (TGF-β1) and Forkhead Box Protein 3 (FOXP3) genes in Iranian patients with allergic rhinitis (AR). Methods: Variations at codons 10 and 25 of TGF-β1 and FOXP3 at positions -3279 A>C and -924 A>G were evaluated in AR patients and compared with controls. In a case-control study, 155 AR patients and 163 allergy- free controls were genotyped using polymerase chain reaction sequence-specific primer (PCR-SSP) technique. Results: The analysis of the frequency of these SNPs showed that the haplotype formed by FOXP3 -3279 A allele occurred significantly more frequently in patients than controls (odds ratio=1.44, 95% CI=1.312-2.66; p=0.001). Conclusion: Our results suggest that polymorphism in FOXP3 gene is associated with susceptibility to AR.