Transcription Factor Assay of Peripheral Blood T cells in Different Groups of Rheumatoid Arthritis Patients

Background: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the joints and other tissues and organs of the body. Previous reports have demonstrated the imbalance of T helper (Th) subsets and Treg activity in the development, progression, and remission of RA. Here, we investigated the mRNA expression of four major transcription factors T-bet (Th1), GATA (Th2), RORc (Th17), and Foxp3 (Treg) in peripheral blood of different groups of RA patients. Materials and methods: In this case-control study, 60 patients with RA, including 20 newly diagnosed, 20 under treatment, and 20 in remission, as well as 20 patients with osteoarthritis, and 20 age- and the sex-matched healthy individual were enrolled. Diagnosis and classification of patients were done according to the American College of Rheumatology criteria. The relative mRNA expression of transcription factors, including T-bet, GATA, RORc, and Foxp3, was measured using qRT-PCR. Results: The relative expression of T-bet in RA patients was significantly increased in healthy controls (P = 0.002), while the relative expression of Foxp3 in RA patients was significantly decreased in healthy controls (P < 0.0001). There was no significant difference in the expression of GATA3 or RORc among RA patients, healthy controls, and osteoarthritis group. Conclusions: The results indicate the importance of Th1 and Treg cells in RA; however, the role of Th17 cells appear to be of little importance in these patients. It seems that Th2 cells do not interfere with RA development.

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The Profile of CD4+CD25+CD127low/- Regulator T Cell and the Associated Expression of Cytokines and Transcription Factors in Immune Thrombocytopenia Murine Model

Blood ◽

10.1182/blood.v124.21.4208.4208 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4208-4208

Author(s):

Liping Ma

Keyword(s):

Transcription Factors ◽

Mrna Expression ◽

Murine Model ◽

Peripheral Blood ◽

Immune Thrombocytopenia ◽

Mononuclear Cells ◽

Treg Cells ◽

Intracellular Cytokines ◽

Proliferation And Differentiation ◽

Daily Intraperitoneal Injection

Abstract Background Regulator T cell (Treg cell) may be associated with immune thrombocytopenia (ITP). Our previous study has showed that the profile of CD4+CD25+CD127low/-Treg cells presented significantly decreased in ITP patients and weakened immunosuppressive activity. This cellular defect about immune modulation may play important roles in the pathogenesis of ITP. The precise reason for these abnormalities remains being elucidated. To further investigate the role of Treg cells in ITP，we detected the profiles of Treg cells and the associated mRNA expression of cytokines and Transcription factors in CD4+CD25+ Treg cells in ITP murine model . Methods 1. The profiles of Treg cell in peripheral blood in ITP patients were examined with flow cytometry through intracellular cytokines analysis. Treg cells were identified as those that were CD4+CD25+CD127low/-. 2. ITP was induced by daily intraperitoneal injection of anti-platelet membrane CD41 antibody（MWReg30）into BALB/c murine and the controls were daily intraperitoneal injection of IgG antibodies. 3. The proportion of Treg cells in peripheral blood and spleen mononuclear cells were measured by FCM analysis. Treg cells were identified as those that were CD4+CD25+CD127low/- 4. The mRNA expression of Treg cells associated transcription factors (Foxp3, Smad7, STAT5 and Akt-1) and cytokines (IL-10, TGF-β) in CD4+CD25+ T cells which were enriched from spleen mononuclear cells were measured by real-time PCR. 5. Statistical analysis. All values were analyzed using SPSS version 18.0 software. We used the Kolmogorov-Smirnov goodness-of-fit model to assess the normality of the data. Because of the data did not show a normal distribution, the values were presented as median (range) and statistical significance was evaluated using a Wilcoxon rank-sum test. Spearman’s test was used for correlation analysis. Differences were considered significant at P <0.05. Results 1. We detected the expression of intracellular cytokines. In peripheral blood of ITP patients, the median of Treg cells was 3.9 % (3.1–6.3 %), respectively, significantly lower than the controls of which that was 6.0 % (5.3–7.85 %, p <0.05). 2. The percentage of CD4+CD25+CD127low/-Treg cells was significantly lower in both splenocyte and peripheral blood of ITP murine as compared with that in normal controls (p<0.05). 3. ITP murine had lower mRNA expression of IL-10, TGF-β and Foxp3 in splenocyte CD4+CD25+T cells (p<0.05). The expression of Smad7 mRNA was significantly higher than the controls. No significantly difference of the STAT5 and Akt-1 mRNA expression were observed between ITP murine and controls both in splenocyte and peripheral blood. Conclusions Our study data supported a low Treg polarization of the immune response in ITP murine model. The lower mRNA expressions of IL-10 and TGF-β indicated that the indirect immunosuppressive effect of Treg cells had impaired. The lower mRNA expressions of TGF-β and Foxp3 accelerated effects on the proliferation and differentiation of Treg cells, and the higher mRNA expression of Smad 7 inhibited the proliferation and differentiation of Treg cells. Results indicated that disorder proliferation and differentiation of Treg cells involved in the pathogenesis of ITP. Disclosures No relevant conflicts of interest to declare.

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CD4+CD25highCD127low/- Treg Cell Frequency from Peripheral Blood Correlates with Disease Activity in Patients with Rheumatoid Arthritis

The Journal of Rheumatology ◽

10.3899/jrheum.110283 ◽

2011 ◽

Vol 38 (12) ◽

pp. 2517-2521 ◽

Cited By ~ 37

Author(s):

SHIN-YA KAWASHIRI ◽

ATSUSHI KAWAKAMI ◽

AKITOMO OKADA ◽

TOMOHIRO KOGA ◽

MAMI TAMAI ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Disease Activity ◽

Treg Cell ◽

Peripheral Blood ◽

Treg Cells ◽

Clinical Disease ◽

Joint Disease ◽

Healthy Controls ◽

Cell Frequency ◽

Clinical Disease Activity

Objective.To investigate whether the frequency of peripheral blood (PB) regulatory T cells (Treg) correlates with the clinical disease activity of rheumatoid arthritis (RA).Methods.PB Treg cells, defined as the CD4+CD25highCD127low/- population, were examined by flow cytometry in 48 patients with RA, including 13 who had never received disease-modifying antirheumatic drugs (DMARD), 19 with active disease who were receiving (n = 14) or had received (n = 5) DMARD, and 16 receiving DMARD whose disease was in remission. The clinical disease activity of the patients was defined by the 28-joint Disease Activity Score (DAS28). The association of DAS28, C-reactive protein (CRP), or erythrocyte sedimentation rate (ESR) with the frequency of PB Treg cells was examined.Results.The frequency of PB Treg cells in patients with RA was significantly low compared with that of healthy controls (n = 14). Among the 3 populations of patients with RA, Treg cell frequency was lowest in patients with active RA. In contrast, the Treg cell frequency of patients with RA in remission was similar to that of healthy controls. Accordingly, the frequency of CD4+CD25highCD127low/- Treg cells negatively correlated with DAS28, CRP, and ESR in patients with RA.Conclusion.The data suggest that Treg cells, defined as the CD4+CD25highCD127low/- population, may contribute to the pathogenesis of RA and be an indicator of disease activity.

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Aberrant Expression of MicroRNAs in CD4+ Cells May Contribute to the Imbalance of Th17/Treg Cells in Primary Immune Thrombocytopenia

Blood ◽

10.1182/blood-2018-99-115569 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 1140-1140

Author(s):

Mingqiang Hua ◽

Qi Feng ◽

Ju Li ◽

Yu Hou ◽

Shuwen Wang ◽

...

Keyword(s):

Peripheral Blood ◽

Th17 Cells ◽

Culture Medium ◽

Treg Cells ◽

Healthy Controls ◽

Cd4 Cells ◽

Rt Pcr ◽

Aberrant Expression ◽

Relative Expression ◽

Regulated Expression

Abstract Backgrounds:Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease characterized by reduced platelet count and an increased risk of bleeding. The imbalance of Treg/Th17 cells has been demonstrated in ITP, but the mechanism of Th17/Treg cells imbalance is still not clear. In this study, we aimed to investigate whether the expression of helper T (Th) or Treg cell-related microRNAs, such as miR-183-96-182 cluster, miR-17-5p, miR-99a, miR-146-5p, miR-155-5p, miR-181-5p, and miR-326, regulates the ratio of Th17/Treg in CD4+ T cells and could be used to evaluate the clinical implications of ITP patients. Methods: Peripheral blood was obtained from 54 patients with active ITP and 34 healthy controls. Peripheral blood mononuclear cells (PBMCs) were isolated using Ficoll density-gradient centrifugation and the CD4+ cells were separated by immuno-magnetic microbeads selection. Amplification technique of RT-PCR using stem-loop primers was applied to detect the relative expression of microRNAs (miR-17-5p, miR-99a, miR-96-5p, miR-146a-5p, miR-155-5p, miR-181a-5p, miR-182-5p, miR-183-5, miR-326) and U6 was normalized as control for miRNA quantification. The frequencies of Th17 and Treg cells in peripheral blood were analyzed by flow cytometry. The mRNA expression levels of Il-6, Il-10, Il-17, Rorγ-t and Foxp-3 in CD4+ cells were determined by RT-PCR. Platelet autoantibodies specific for GPIIb/IIIaor GPIb/IX were measured using MAIPA method. CD4+ cells were transfected with miRNAs (miR-99a, miR-182-5p, miR-183-5), mimics or inhibitors, which were used to detect the function of miRNAs. Cytokines in culture medium were determined by ELISA. Results: Our results showed that the relative expression of miR-182-5p and miR-183-5p in CD4+ cells was significantly increased in active ITP patients, compared to healthy controls (miR-182-5p, median 9.2678 vs 5.2723, p < 0.05, Fig. 1a; miR-183-5p, median 5.4435 vs 2.009, p < 0.05, Fig. 1b). In addition, the relative expression of miR-99a in ITP patients was lower than that of healthy controls (median 3.4214 vs 7.9648, p < 0.05; Fig. 1c). Moreover, the frequency of Treg cells decreased significantly in ITP patients compared to those in controls (1.89±1.59% vs 4.12±1.42%, p < 0.05; Fig. 2a), and the percentage of Treg cells was positively correlated with the relative expression of miR-99a in ITP patients(r=0.461, p< 0.05; Fig. 2c) and health controls(r=0.729, p< 0.05; Fig. 2d). Though the percentage of Th17 cells increased in ITP patients compared to the health controls (3.51±2.13%vs 1.85±0.63%, p < 0.05; Fig. 2b), there was no correlation between the percentage of Th17 and the relative expression of microRNAs in ITP patients or health controls. Besides, there was no correlation between the expression of mRNAs (Il-10, Il-17, Rorγ-t and Foxp-3) and microRNAs (miR-99a, miRNA-182-5p or miR-183-5p). No significant correlation was found between the microRNAs expression and platelets counts or different autoantibody subsets in ITP patients. The relative expression of other microRNAs (miR-17-5p, miR-96-5p, miR-146a-5p, miR-155-5p, miR-181-5p, miR-326) revealed no difference in CD4+ cells between ITP patients and health controls. Furthermore, the down-regulated expression of miR-183-5p with inhibitors promoted to the differentiation of Th17 cells(Fig. 3a), while up-regulated expression of miR-99a with mimics contributed to Treg cells in CD4+ cells from ITP patients (Fig. 3b). Meanwhile, the IL-17A in culture medium decreased in inhibitor group of miR-183-5p or miR-183-5p. However, miR-182-5p inhibitor had no effect on the differentiation of Th17 cells. Conclusions: Our results show the abnormal expression of microRNAs (miR-99a, miRNA-182-5p and miR-183-5p) in CD4+ cells and the miR-99a was closely correlated with the Treg cells. The aberrant expression of microRNAs may contribute to the imbalance of Th17/Treg cells in the development of ITP patients and potentially constitute a novel therapeutic target. Disclosures No relevant conflicts of interest to declare.

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Function of regulatory T-cells improved by dexamethasone in Graves' disease

Acta Endocrinologica ◽

10.1530/eje-11-0879 ◽

2012 ◽

Vol 166 (4) ◽

pp. 641-646 ◽

Cited By ~ 20

Author(s):

Yun Hu ◽

Wei Tian ◽

Ling-Ling Zhang ◽

Hao Liu ◽

Guo-Ping Yin ◽

...

Keyword(s):

T Cells ◽

Mrna Expression ◽

Treg Cell ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Cell Function ◽

Treg Cells ◽

Th2 Cells ◽

Graves Disease ◽

Treg Cell Function

ObjectiveIntrathyroid injection of dexamethasone (DEX) has been used to treat Graves' disease (GD); however, the mechanism of this treatment remains poorly understood. The objective of this study was to investigate the effects of DEX on the function of regulatory T (Treg) cells (CD4+CD25+T cells) in patients with GD.MethodsPeripheral blood was obtained from 20 patients with GD, and peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll–Hypaque density gradient separation. CD4+CD25–/CD4+CD25+T cells were isolated by immunomagnetic selection and DEX was co-cultured with PBMCs or isolated T-cells for 72 h. Treg cell function was analyzed using the proliferation rate of CD4+CD25–T cells.ResultsThe proportion of Treg cells and the transcription factor forkhead box P3 (FOXP3) mRNA expression in PBMCs decreased in GD patients compared with healthy subjects, and Treg cell function was impaired in patients with GD. Although the proportion of Treg cells and FOXP3 mRNA expression in PBMCs did not increase, the function of Treg cells improved after the treatment with DEX. Moreover, the proportion of T-helper 2 (Th2) cells was decreased by the DEX treatment.ConclusionsDEX could effectively improve the function of Treg cells and set up a new balance of Th1/Th2 in GD patients. This study might help to further understand the immune mechanism of the intrathyroid injection of DEX in the treatment of GD and facilitate the potential use of this therapy.

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Assessment of peripheral blood T regulatory cells (Tregs) in PNET/Ewing sarcoma: A prospective study.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.9580 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 9580-9580

Author(s):

Tilak Tvsvgk ◽

Surender Kumar Sharawat ◽

Ritu Gupta ◽

Sandeep Agarwala ◽

Shah Alam Khan ◽

...

Keyword(s):

Metastatic Disease ◽

Peripheral Blood ◽

Venous Blood ◽

Flow Cytometric Analysis ◽

Treg Cells ◽

Healthy Controls ◽

Female Ratio ◽

Entire Cohort ◽

Treg Frequency ◽

Significant Difference

9580 Background: Tregs in bone marrow have been previously evaluated in PNET patients; however, data on peripheral blood ccirculating Tregs is lacking. The objective of our study was to determine baseline Treg frequency in PNET patients and correlate the same with patient characteristics and outcome. Methods: Samples of 5ml venous blood were obtained from 38 newly diagnosed PNET patients at diagnosis along with six healthy controls. Flow cytometric analysis was done for detecting Treg cells [CD4+CD25+FoxP3+]. Results: Thirty-eight patients with median age 17 years; male/female ratio of 5.5:1 had significantly higher baseline Tregs than healthy controls [9.17%±.3.08 vs 3.16±1.49%; p=<0.0001]. Eight patients (21.1%) had fever at baseline presentation. The disease was extra-skeletal in one and metastatic at baseline in 11 (28.9%) patients. Ten patients relapsed on standard protocol of therapy and seven died. The median Treg frequency was 8.84% (Range: 2.49-16.31). When the Tregs were categorized as high and low based on the median value, patients with fever had a significantly higher Tregs than those without fever [11.3%±.3.5% vs 8.6% ±. 2.7%; p=0.02]. No significant association of peripheral blood Treg cells frequency was noted with other factors like age, sex, metastatic disease, relapse or death. The EFS was 55% and OS 70% of the entire cohort at a median follow up of 14 months. There was no significant difference in the EFS or OS between the high and low Treg cell groups [EFS- 52% vs 64%; p=0.99 and OS-75% vs 70%; p=0.26]. Conclusions: This is the first study on circulating Tregs in PNET, and it shows that the peripheral blood Treg frequencies are higher in these patients as compared to healthy controls. Further, PNET patients with fever had significantly higher Treg frequency. However, Tregs did not differ with respect to metastatic disease at presentation, EFS or OS.

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Comprehensive Evaluation of Different T-Helper Cell Subsets Differentiation and Function in Rheumatoid Arthritis

Journal of Biomedicine and Biotechnology ◽

10.1155/2012/535361 ◽

2012 ◽

Vol 2012 ◽

pp. 1-6 ◽

Cited By ~ 24

Author(s):

Junwei Chen ◽

Junxia Li ◽

Huiying Gao ◽

Caihong Wang ◽

Jing Luo ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Th17 Cells ◽

Comprehensive Evaluation ◽

Autoimmune Disorder ◽

Cell Interaction ◽

Treg Cells ◽

Th2 Cells ◽

Das28 Score ◽

Significant Difference ◽

And Function

Rheumatoid arthritis (RA) is the most common autoimmune disorder. Loss of Th1/Th2 and Th17/Treg balance has been reported in several inflammatory autoimmune diseases. This study was to investigate Th1, Th2, Th17, and Treg differentiation and related cytokines in RA patients. The frequencies of Th1, Th2, Th17, and Treg cells in peripheral blood of RA patients (n=76) and healthy controls (n=18) were determined by flow cytometry. Eight serum cytokines were analyzed using cytometric bead array. The results demonstrated that RA patients exhibited increased peripheral Th1/Th17 cells and Th1/Th17-related cytokines. However, Th1 cells only reached significant difference at advanced stage, but Th17 at all stages, suggesting more important roles in Th17 cells. For Th2 and Treg cells, there was a different function pattern in RA progression. Although with the increase of DAS28 score, Th2 cell experienced some degree of decrease in RA patients, no significant difference was observed. IL-4 and IL-10 showed a significant increase in RA patients. These indicated that Th2 cells might exert immunosuppression effects mainly by secreting cytokines. Treg cells were found significantly decreased in RA patients, but no difference was observed in TGF-βexpression, indicating a cell-cell interaction pattern in Treg cell.

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Single Immunoglobulin IL-1-Related Receptor (SIGIRR) Gene rs7396562 Polymorphism and Expression Level in Rheumatoid Arthritis

BioMed Research International ◽

10.1155/2021/6683148 ◽

2021 ◽

Vol 2021 ◽

pp. 1-6

Author(s):

Xiaoke Yang ◽

Mingyue Zhang ◽

Shengqian Xu ◽

Haifeng Pan ◽

Ruixue Leng ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Mrna Expression ◽

Chinese Population ◽

Quantitative Polymerase Chain Reaction ◽

Healthy Controls ◽

Allelic Discrimination Assay ◽

Allelic Discrimination ◽

Expression Levels ◽

Significant Difference ◽

Mrna Expression Levels

Objectives. The aim of our study was to investigate the association of single-nucleotide polymorphism (SNP) and mRNA expression profile of single immunoglobulin IL-1-related receptor (SIGIRR) in rheumatoid arthritis (RA) in a Chinese population. Methods. SIGIRR rs7396562 polymorphism was genotyped using TaqMan allelic discrimination assay in 517 RA patients and 601 healthy controls. Simultaneously, the SIGIRR mRNA expression levels of 79 RA patients and 76 healthy controls were examined by real-time quantitative polymerase chain reaction (RT-qPCR). Results. The frequency of SIGIRR rs7396562 T allele was significantly higher in RA patients compared with healthy controls (T versus G: OR = 1.277 , 95 % CI = 1.079 − 1.511 , P = 0.004 ). The TT genotype of SIGIRR rs7396562 was more frequent in RA patients than in healthy controls ( OR = 1.547 , 95 % CI = 1.107 − 2.163 , P = 0.011 ). Moreover, we also found a significant difference in the recessive model (TT versus TG+GG: OR = 1.439 , 95 % CI = 1.122 − 1.847 , P = 0.004 ). However, no significant evidence was observed for the association of the SIGIRR rs7396562 with RA in dominant model (TT+TG versus GG: OR = 1.275 , 95 % CI = 0.947 − 1.717 , P = 0.109 ). Further analysis showed no association between SIGIRR rs7396562 polymorphism and laboratory parameters of RA patients (all P > 0.05 ). The mRNA expression of SIGIRR was decreased in PBMCs of patients with RA when compared to healthy controls ( Z = − 2.459 , P = 0.014 ). No significant differences in SIGIRR mRNA expression levels were observed in patients with RA with different genotypes ( P = 0.280 ). Conclusions. Our findings demonstrated that the dysregulation of SIGIRR might be associated with the pathogenesis of RA, and SIGIRR rs7396562 polymorphism might contribute to RA susceptibility in the Chinese population.

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Regulatory T Cells Fail to Suppress Fast Homeostatic Proliferation In Vitro

Life ◽

10.3390/life11030245 ◽

2021 ◽

Vol 11 (3) ◽

pp. 245

Author(s):

Daniil Shevyrev ◽

Valeriy Tereshchenko ◽

Elena Blinova ◽

Nadezda Knauer ◽

Ekaterina Pashkina ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

T Cells ◽

T Cell ◽

Regulatory T Cells ◽

Autoimmune Diseases ◽

Peripheral Blood ◽

Treg Cells ◽

Homeostatic Proliferation ◽

Suppressive Activity ◽

Healthy Donors

Homeostatic proliferation (HP) is a physiological process that reconstitutes the T cell pool after lymphopenia involving Interleukin-7 and 15 (IL-7 and IL-15), which are the key cytokines regulating the process. However, there is no evidence that these cytokines influence the function of regulatory T cells (Tregs). Since lymphopenia often accompanies autoimmune diseases, we decided to study the functional activity of Tregs stimulated by HP cytokines from patients with rheumatoid arthritis as compared with that of those from healthy donors. Since T cell receptor (TCR) signal strength determines the intensity of HP, we imitated slow HP using IL-7 or IL-15 and fast HP using a combination of IL-7 or IL-15 with anti-CD3 antibodies, cultivating Treg cells with peripheral blood mononuclear cells (PBMCs) at a 1:1 ratio. We used peripheral blood from 14 patients with rheumatoid arthritis and 18 healthy volunteers. We also used anti-CD3 and anti-CD3 + IL-2 stimulation as controls. The suppressive activity of Treg cells was evaluated in each case by the inhibition of the proliferation of CD4+ and CD8+ cells. The phenotype and proliferation of purified CD3+CD4+CD25+CD127lo cells were assessed by flow cytometry. The suppressive activity of the total pool of Tregs did not differ between the rheumatoid arthritis and healthy donors; however, it significantly decreased in conditions close to fast HP when the influence of HP cytokines was accompanied by anti-CD3 stimulation. The Treg proliferation caused by HP cytokines was lower in the rheumatoid arthritis (RA) patients than in the healthy individuals. The revealed decrease in Treg suppressive activity could impact the TCR landscape during lymphopenia and lead to the proliferation of potentially self-reactive T cell clones that are able to receive relatively strong TCR signals. This may be another explanation as to why lymphopenia is associated with the development of autoimmune diseases. The revealed decrease in Treg proliferation under IL-7 and IL-15 exposure can lead to a delay in Treg pool reconstitution in patients with rheumatoid arthritis in the case of lymphopenia.

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Over-expression of IL-6 coding gene in the peripheral blood of migraine with aura patients

Human Antibodies ◽

10.3233/hab-210442 ◽

2021 ◽

pp. 1-5

Author(s):

Mahdi Ramezani ◽

Alireza Komaki ◽

Mohammad Mahdi Eftekharian ◽

Mehrdokht Mazdeh ◽

Soudeh Ghafouri-Fard

Keyword(s):

Migraine With Aura ◽

Peripheral Blood ◽

Healthy Subjects ◽

Migraine Without Aura ◽

P Value ◽

Healthy Controls ◽

Over Expression ◽

Significant Difference ◽

Male Patients ◽

Years Lived With Disability

Migraine is a common disorder which is placed among the top ten reasons of years lived with disability. Cytokines are among the molecules that contribute in the pathophysiology of migraine. In the current study, we evaluated expression levels of IL-6 coding gene in the peripheral blood of 120 migraine patients (54 migraine without aura and 66 migraine with aura patients) and 40 healthy subjects. No significant difference was detected in expression of IL-6 between total migraine patients and healthy controls (Posterior beta = 0.253, P value = 0.199). The interaction effect between gender and group was significant (Posterior beta =-1.274, P value = 0.011), therefore, we conducted subgroup analysis within gender group. Such analysis revealed that while expression of this gene is not different between male patients and male controls (Posterior beta =-0.371, P value > 0.999), it was significantly over-expressed in female patients compared with female controls (Posterior beta = 0.86, P= 0.002). Expression of IL-6 was significantly higher in patients with aura compared with controls (Posterior beta = 0.63, adjusted P value = 0.019). However, expression of this cytokine coding gene was not different between patients without aura and healthy subjects (Posterior beta = 0.193, adjusted P value = 0.281). Therefore, IL-6 might be involved in the pathophysiology of migraine among females and migraine with aura among both sexes.

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Identification of NURR1 (Exon 4) and FOXA1 (Exon 3) Haplotypes Associated with mRNA Expression Levels in Peripheral Blood Lymphocytes of Parkinson’s Patients in Small Indian Population

Parkinson s Disease ◽

10.1155/2017/6025358 ◽

2017 ◽

Vol 2017 ◽

pp. 1-8 ◽

Cited By ~ 3

Author(s):

Jayakrishna Tippabathani ◽

Jayshree Nellore ◽

Vaishnavie Radhakrishnan ◽

Somashree Banik ◽

Sonia Kapoor

Keyword(s):

Mrna Expression ◽

Peripheral Blood ◽

Peripheral Blood Lymphocytes ◽

Coding Region ◽

Male And Female ◽

Blood Lymphocytes ◽

Coding Regions ◽

Significant Difference ◽

Exon 4 ◽

Foxa1 Expression

Here, we study the expression of NURR1 and FOXA1 mRNA in peripheral blood lymphocytes and its haplotypes in coding region in a small Chennai population of India. Thirty cases of Parkinson’s patients (PD) with anti-PD medications (20 males aged65.85±1.19and 10 females aged65.7±1.202) and 30 age matched healthy people (20 males aged68.45±1.282and 10 females aged65.8±1.133) were included. The expression of NURR1 and FOXA1 in PBL was detected by Q-PCR and haplotypes were identified by PCR-SSCP. In the 30 PD cases examined, NURR1 and FOXA1 expression was significantly reduced in both male and female PD patients. However, NURR1 (57.631% reduced in males; 28.93% in females) and FOXA1 (64.42% in males; 55.76% in females) mRNA expression did differ greatly between male and female PD patients. Polymorphisms were identified at exon 4 of the NURR1 and at exon 3 of the FOXA1, respectively, in both male and female patients. A near significant difference in SSCP patterns between genders of control and PD population was analyzed suggesting that further investigations of more patients, more molecular markers, and coding regions should be performed. Such studies could potentially reveal peripheral molecular marker of early PD and different significance to the respective genders.

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