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Are programmed cell death 1 gene polymorphisms correlated with susceptibility to rheumatoid arthritis?: A meta-analysis.

ABSTRACT: Several studies investigated the relationship between programmed cell death 1 (PDCD1) gene polymorphisms and rheumatoid arthritis (RA) risk, but the results were controversial. To explore whether PDCD1 gene polymorphisms have an effect on RA risk, we conducted this meta-analysis to investigate the relationships between PDCD1 polymorphisms (rs36084323 [PD-1.1?G/A], rs11568821 [PD-1.3?G/A] and rs2227981 [PD-1.5?C/T]) and RA risk under 4 genetic models.PubMed, EMBASE, Web of Science, Cochrane Library China National Knowledge Infrastructure (CNKI), and Chinese Biomedical Literature Database (CBLM) were systematically searched for all eligible case-control studies. The last search was updated on September 10, 2016. Studies were accessed using Newcastle-Ottawa Scale case control study (NOS), and the combined effect size was calculated using STATA software, version 12.0. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to assess the association. Heterogeneity analysis and subgroup analysis were also performed. Sensitivity analysis and publication bias were also performed if necessary.This meta-analysis included 6 studies. The result demonstrated null association between rs36084323 (PD-1.1?G/A) polymorphism and RA susceptibility in all 4 genetic models. With regard to rs11568821 (PD-1.3?G/A), statistically significant association with RA risk was observed under allele model in Caucasians (allele model A vs G, OR = 1.19, 95% CI = 1.03-1.41). There was no significant association between rs2227981 (PD-1.5?C/T) polymorphism and RA risk.The present study suggests that mutant A allele in rs11568821 (PD-1.3?G/A) might increase the susceptibility to RA in Caucasians.

SUBMITTER: Zou Y

PROVIDER: S-EPMC5585485 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Are programmed cell death 1 gene polymorphisms correlated with susceptibility to rheumatoid arthritis?: A meta-analysis.

Zou Yuming Y Zhang Ziteng Z Liu Yangang Y Liu Denghui D Xu Weidong W

Medicine 20170901 35

<h4>Background</h4>Several studies investigated the relationship between programmed cell death 1 (PDCD1) gene polymorphisms and rheumatoid arthritis (RA) risk, but the results were controversial. To explore whether PDCD1 gene polymorphisms have an effect on RA risk, we conducted this meta-analysis to investigate the relationships between PDCD1 polymorphisms (rs36084323 [PD-1.1 G/A], rs11568821 [PD-1.3 G/A] and rs2227981 [PD-1.5 C/T]) and RA risk under 4 genetic models.<h4>Methods</h4>PubMed, EMB ...[more]

PMID: 28858091

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Project description:IntroductionExtracellular vesicles (EVs) have been recognized as route of communication in the microenvironment. They transfer proteins and microRNAs (miRNAs) between cells, and possess immunoregulatory properties. However, their role in immune-mediated diseases remains to be elucidated. We hypothesized a role for EVs in the rheumatoid arthritis (RA) joint, potentially involving the development of T cell exhaustion and transfer of the co-inhibitory receptor programmed death 1 (PD-1).MethodsSynovial fluid mononuclear cells (SFMCs) and peripheral blood mononuclear cells (PBMCs) from RA patients were investigated for PD-1 and other markers of T cell inhibition. EVs were isolated from RA plasma and synovial fluid. In addition, healthy control (HC) and RA PBMCs and SFMCs were cultured to produce EVs. These were isolated and investigated by immunogold electron microscopy (EM) and also co-cultured with lymphocytes and PD-1 negative cells to investigate their functions. Finally, the miRNA expression profiles were assessed in EVs isolated from RA and HC cell cultures.ResultsCells from the RA joint expressed several T cell co-inhibitory receptors, including PD-1, TIM-3, and Tigit. ELISA demonstrated the presence of PD-1 in EVs from RA plasma and synovial fluid. Immunogold EM visualized PD-1 expression by EVs. Co-culturing lymphocytes and the PD-1 negative cell line, U937 with EVs resulted in an induction of PD-1 on these cells. Moreover, EVs from RA PBMCs increased proliferation in lymphocytes when co-cultured with these. All EVs contained miRNAs associated with PD-1 and other markers of T cell inhibition and the content was significantly lower in EVs from RA PBMCs than HC PBMCs. Stimulation of the cells increased the miRNA expression. However, EVs isolated from stimulated RA SFMCs did not change their miRNA expression profile to the same extend.ConclusionEVs carrying both the PD-1 receptor and miRNAs associated with T cell inhibition were present in RA cell cultures. Upon stimulation, these miRNAs failed to be upregulated in EVs from RA SFMCs. This was in line with increased expression of T cell co-inhibitory markers on SFMCs. In conclusion, we suggest EVs to play a significant role in the RA microenvironment, potentially favoring the progression of T cell exhaustion.

Project description:Aims: Rheumatoid arthritis (RA) is characterized by cartilage and bone damage leading to disability. Here, the association between microRNA (miRNA) polymorphisms and susceptibility to RA was evaluated by performing an updated meta-analysis and systematic review. Main methods: An electronic search of databases including PubMed and Embase was performed from inception to December 8, 2017 to retrieve studies investigating the association between miRNA polymorphisms and RA risk. Two reviewers independently screened literature according to the inclusion and exclusion criteria and extracted data. The meta-analysis was conducted using Stata 14.0 software. Key findings: Thirteen case-control studies with 2660 cases and 4098 controls were screened out after a systematic search. One study from the miR-146a rs2910164 G > C polymorphism group and two from the miR-499 rs3746444 T > C polymorphism group were excluded because of deviations from Hardy-Weinberg equilibrium. Pooled analysis demonstrated that miR-146a rs2910164 G > C polymorphism was not significantly associated with susceptibility to RA. However, a significant association was observed between miR-499 rs3746444 T > C polymorphism and RA risk (C vs. T: OR = 1.22, 95% CI = 1.05-1.42, P = 0.008; TC vs. TT: OR = 1.26, 95% CI = 1.05-1.50, P = 0.011; TC/CC vs. TT: OR = 1.26, 95% CI = 1.07-1.5, P = 0.007). Subgroup analysis based on ethnicity showed no significant association between miR-499 T > C polymorphism and susceptibility to RA in the Asian population (P > 0.05). However, in Caucasian population, the C allele in the miR-499 T > C polymorphism was a contributor to RA susceptibility in some genetic models (C vs. T: OR = 1.64, 95% CI = 1.28-2.11, P < 0.001; TC vs. TT: OR = 1.95, 95% CI = 1.40-2.71, P < 0.001; TC/CC vs. TT: OR = 1.96, 95% CI = 1.43-2.69, P < 0.001). Significance: The miR-146a rs2910164 G > C polymorphism was not associated with susceptibility to RA. In the Caucasian population, the C allele in the miR-499 T > C polymorphism contributed to RA susceptibility.

Project description:BackgroundImmunotherapy has shown promising efficacy in patients with nasopharyngeal carcinoma (NPC). Lymphocyte activating 3 gene (LAG-3) represents a significant immune target, however, its relationship with NPC remains unclear. This study aimed to evaluate LAG-3 expression in NPC and its association with CD3+ tumor-infiltrating lymphocytes (TILs), Granzyme B (GZMB), programmed death ligand 1 (PD-L1), and programmed death 1 (PD-1) expression.MethodsA total of 182 patients with NPC from Sun Yat-sen University Cancer Center, China, were included in this retrospective study. LAG-3 expression in 15 NPC cell lines and LAG-3, CD3+ TILs, GZMB, PD-L1 and PD-1 in clinical samples were estimated using immunohistochemistry. The Chi-square test was used to estimate the association between LAG-3, other biomarkers, and clinical characteristics. Survival analysis was performed using the Kaplan-Meier method and the Cox regression model.ResultsLAG-3 was negatively expressed in all of the 15 NPC cell lines, whereas, 147 patients with NPC (80.8%) exhibited high LAG-3 expression on TILs from tumor tissues. Male patients and those who were EBV-positive presented higher LAG-3 expression. Correlation analyses showed that LAG-3 expression was related to PD-1 expression on TILs, as well as, PD-L1 expression on tumor cells (TCs) and TILs. Both the univariate and multivariate Cox models indicated that pathological type III (P = 0.036), higher LAG-3 on TILs (P < 0.001), higher PD-L1 on TCs (P = 0.027), and higher PD-1 on TILs (P < 0.001) were associated with poorer disease-free survival (DFS). However, lower PD-L1 expression on TILs was related to superior DFS only in the univariate Cox analyses (P = 0.002).ConclusionHigher LAG-3 and PD-1 on TILs, and higher PD-L1 expression on TCs, and pathological type III were identified as independent risk factors for poorer DFS in NPC patients. Our data demonstrate that LAG-3 is a promising inhibitory receptor that may play an important role in anti-NPC therapy.

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Are programmed cell death 1 gene polymorphisms correlated with susceptibility to rheumatoid arthritis?: A meta-analysis.

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Are programmed cell death 1 gene polymorphisms correlated with susceptibility to rheumatoid arthritis?: A meta-analysis.

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