-
Frontiers in Immunology 2021Besides recurrent infections, a proportion of patients with Common Variable Immunodeficiency Disorders (CVID) may suffer from immune dysregulation such as... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Besides recurrent infections, a proportion of patients with Common Variable Immunodeficiency Disorders (CVID) may suffer from immune dysregulation such as granulomatous-lymphocytic interstitial lung disease (GLILD). The optimal treatment of this complication is currently unknown. Experienced-based expert opinions have been produced, but a systematic review of published treatment studies is lacking.
GOALS
To summarize and synthesize the published literature on the efficacy of treatments for GLILD in CVID.
METHODS
We performed a systematic review using the PRISMA guidelines. Papers describing treatment and outcomes in CVID patients with radiographic and/or histologic evidence of GLILD were included. Treatment regimens and outcomes of treatment were summarized.
RESULTS
6124 papers were identified and 42, reporting information about 233 patients in total, were included for review. These papers described case series or small, uncontrolled studies of monotherapy with glucocorticoids or other immunosuppressants, rituximab monotherapy or rituximab plus azathioprine, abatacept, or hematopoietic stem cell transplantation (HSCT). Treatment response rates varied widely. Cross-study comparisons were complicated because different treatment regimens, follow-up periods, and outcome measures were used. There was a trend towards more frequent GLILD relapses in patients treated with corticosteroid monotherapy when compared to rituximab-containing treatment regimens based on qualitative endpoints. HSCT is a promising alternative to pharmacological treatment of GLILD, because it has the potential to not only contain symptoms, but also to resolve the underlying pathology. However, mortality, especially among immunocompromised patients, is high.
CONCLUSIONS
We could not draw definitive conclusions regarding optimal pharmacological treatment for GLILD in CVID from the current literature since quantitative, well-controlled evidence was lacking. While HSCT might be considered a treatment option for GLILD in CVID, the risks related to the procedure are high. Our findings highlight the need for further research with uniform, objective and quantifiable endpoints. This should include international registries with standardized data collection including regular pulmonary function tests (with carbon monoxide-diffusion), uniform high-resolution chest CT radiographic scoring, and uniform treatment regimens, to facilitate comparison of treatment outcomes and ultimately randomized clinical trials.
Topics: Clinical Trials as Topic; Combined Modality Therapy; Common Variable Immunodeficiency; Disease Management; Disease Susceptibility; Humans; Lung Diseases, Interstitial; Prognosis
PubMed: 33936030
DOI: 10.3389/fimmu.2021.606099 -
Inflammation Research : Official... Sep 2018Inflammatory bowel disease (IBD) is a chronic inflammatory disease, which involves the gut and comprises of Crohn's disease (CD) and ulcerative colitis (UC). Immune... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Inflammatory bowel disease (IBD) is a chronic inflammatory disease, which involves the gut and comprises of Crohn's disease (CD) and ulcerative colitis (UC). Immune cells, including natural killer (NK) cells, play an important role in the pathogenesis of the disease. Killer immunoglobulin-like receptors (KIRs) are NK cell surface receptors, which ligate to the class I major histocompatibility complex (MHC) and have inhibitory or activating effects on the NK cells. The aim of this study was to perform a meta-analysis of the six studies evaluating the association in the polymorphisms of these KIR genes and the IBD risk (4 UC and 5 CD studies).
METHODS
A systematic search was conducted in the electronic databases to find all the studies on the KIR gene polymorphism in IBD patients prior to December 2017. The odds ratio (OR) and 95% confidence interval (CI) were used to find any association between KIR gene polymorphisms and the IBD risk.
RESULTS
Following extraction of the data from the studies, which were screened by inclusion and exclusion criteria, collectively 432 patients and 886 controls for UC and 1677 patients and 1308 controls for CD were included in the meta-analysis. The statistical evaluation demonstrated positive associations between 2DL5 (OR=1.31, 95% CI=1.01-1.69) and 2DS1 (OR=1.33, 95% CI=1.01-1.76) members of KIR genes and UC risk, as well a negative association between 2DS3 gene and CD risk was detected (OR=0.74, 95% CI=0.60-0.90).
CONCLUSIONS
There are positive associations between 2DL5 and 2DS1 members of KIR genes and UC risk and a negative association between 2DS3 and CD risk.
Topics: Genetic Predisposition to Disease; Humans; Inflammatory Bowel Diseases; Odds Ratio; Receptors, KIR
PubMed: 29869094
DOI: 10.1007/s00011-018-1162-7 -
Medicine Apr 2017A number of studies had reported the association between tumor necrosis factor-alpha (TNF-α) gene polymorphisms and ischemic heart disease (IHD) risk. However, the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
A number of studies had reported the association between tumor necrosis factor-alpha (TNF-α) gene polymorphisms and ischemic heart disease (IHD) risk. However, the results remained controversial. Therefore, we performed a systematic review with multiple meta-analyses to provide the more precise estimations of the relationship.
METHODS
We systematically searched electronic databases (PubMed, the Web of Science, EMBASE, Medline, Chinese National Knowledge Infrastructure, WanFang and ChongQing VIP Database) for relevant studies published up to February 2017. The odds ratios (ORs) and 95% confidence intervals (CIs) were estimated for assessing the association. The present meta-analysis was performed using STATA 12.0 software.
RESULTS
In total, 45 articles with 17,375 cases and 15,375 controls involved were included. Pooled ORs revealed a significant association between TNF-α -308G/A gene polymorphism and IHD (A vs. G: OR = 1.22, 95% CI = 1.10-1.35; (AA + GA) vs. GG: OR = 1.18, 95% CI = 1.03-1.36; (AA vs. (GA+GG): OR = 1.37, 95% CI = 1.08-1.75)), indicating that the TNF-α -308A allele might be an important risk factor for IHD. No association between other TNF-α gene polymorphisms and susceptibility to IHD were observed. No publication bias were found. Sensitivity analyses indicated that our results were stable.
CONCLUSION
The present study indicated a possible association between the TNF-α -308G/A gene polymorphism and IHD risk. However, evidence was limited to confirm the role of TNF-α -238G/A, -857C/T, -863C/A, -1031T/C and other TNF-α gene polymorphisms in the risk of IHD.
Topics: Genetic Predisposition to Disease; Humans; Myocardial Ischemia; Polymorphism, Genetic; Tumor Necrosis Factor-alpha
PubMed: 28383437
DOI: 10.1097/MD.0000000000006569 -
Medicine Sep 2022Glutathione S-transferases (GSTs) genes single-nucleotide polymorphisms (SNPs) have been connected with the susceptibility of nonalcoholic fatty liver disease (NAFLD),... (Meta-Analysis)
Meta-Analysis
Association of glutathione S-transferases (GSTT1, GSTM1 and GSTP1) genes polymorphisms with nonalcoholic fatty liver disease susceptibility: A PRISMA-compliant systematic review and meta-analysis.
BACKGROUND
Glutathione S-transferases (GSTs) genes single-nucleotide polymorphisms (SNPs) have been connected with the susceptibility of nonalcoholic fatty liver disease (NAFLD), but with inconsistent results across the current evidences. The present work was schemed to explore the association between GSTs genes polymorphisms and the NAFLD vulnerability via meta-analysis.
METHODS
PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure and Wanfang were retrieved for eligible literatures previous to March 10, 2021. The odds ratio (OR) of the dichotomic variables and the standardized mean difference of quantitative variables with corresponding 95% confidence intervals (95%CIs) were computed to evaluate the strength of the associations. The quality of included studies were assessed via using Newcastle-Ottawa Scale (NOS).
RESULTS
In total, 7 case-control studies encompassing 804 NAFLD patients and 1362 disease-free controls in this meta-analysis. Ultimately, this analysis included 6, 5 and 5 studies for GSTM1, GSTT1 and GSTP1 polymorphisms, respectively. The pooled data revealed that the GSTs genes SNPs had conspicuous associations with NAFLD susceptibility: for GSTM1, null versus present, OR = 1.46, 95%CI 1.20 to 1.79, P = .0002; for GSTT1, null versus present, OR = 1.34, 95%CI 1.06 to 1.68, P = .01; for GSTP1, Ile/Val or Val/Val versus Ile/Ile, OR = 1.60, 95%CI 1.23 to 2.09, P = .0005.
CONCLUSION
This work revealed that the GSTM1 null, GSTT1 null and GSTP1-Val genotypes might be related to increased NAFLD susceptibility.
Topics: Humans; Case-Control Studies; Genetic Predisposition to Disease; Genotype; Glutathione; Glutathione S-Transferase pi; Glutathione Transferase; Non-alcoholic Fatty Liver Disease; Polymorphism, Single Nucleotide; Risk Factors
PubMed: 36197156
DOI: 10.1097/MD.0000000000030803 -
British Journal of Sports Medicine Jul 2015Recurrent instability following a first-time anterior traumatic shoulder dislocation may exceed 26%. We systematically reviewed risk factors which predispose this... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Recurrent instability following a first-time anterior traumatic shoulder dislocation may exceed 26%. We systematically reviewed risk factors which predispose this population to events of recurrence.
METHODS
A systematic review of studies published before 1 July 2014. Risk factors which predispose recurrence following a first-time traumatic anterior shoulder dislocation were documented and rates of recurrence were compared. Pooled ORs were analysed using random-effects meta-analysis.
RESULTS
Ten studies comprising 1324 participants met the criteria for inclusion. Recurrent instability following a first-time traumatic anterior shoulder dislocation was 39%. Increased risk of recurrent instability was reported in people aged 40 years and under (OR=13.46), in men (OR=3.18) and in people with hyperlaxity (OR=2.68). Decreased risk of recurrent instability was reported in people with a greater tuberosity fracture (OR=0.13). The rate of recurrent instability decreased as time from the initial dislocation increased. Other factors such as a bony Bankart lesion, nerve palsy and occupation influenced rates of recurrent instability.
CONCLUSIONS
Sex, age at initial dislocation, time from initial dislocation, hyperlaxity and greater tuberosity fractures were key risk factors in at least two good quality cohort studies resulting in strong evidence as concluded in the GRADE criteria. Although bony Bankart lesions, Hill Sachs lesions, occupation, physiotherapy treatment and nerve palsy were risk factors for recurrent instability, the evidence was weak using the GRADE criteria-these findings relied on poorer quality studies or were inconsistent among studies.
Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Disease Susceptibility; Female; Humans; Joint Instability; Male; Middle Aged; Recurrence; Risk Factors; Sex Factors; Shoulder Dislocation; Young Adult
PubMed: 25900943
DOI: 10.1136/bjsports-2014-094342 -
Cytokine Nov 2023Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory disease with high morbidity and mortality rates worldwide. Cytokines, which are the main... (Meta-Analysis)
Meta-Analysis Review
Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory disease with high morbidity and mortality rates worldwide. Cytokines, which are the main regulators of immune responses, play crucial roles in inflammatory diseases such as COPD. Moreover, certain genetic variations can alter cytokine expression, and changes in cytokine level or function can affect disease susceptibility. Therefore, investigating the association between genetic variations and disease progression can be useful for prevention and treatment. Several studies have explored the association between common genetic variations in cytokine genes and COPD susceptibility. In this study, we summarized the reported studies and, where possible, conducted a systematic review and meta-analysis to evaluate the genetic association between various cytokines and COPD pathogenesis. We extracted relevant articles from PubMed and Google Scholar databases using a standard systematic search strategy. We included a total of 183 studies from 78 separate articles that evaluated 50 polymorphisms in 12 cytokine genes in this study. Our analysis showed that among all reported cytokine polymorphisms (including TNF-α, TGF-β, IL1, IL1RN, IL4, IL4R, IL6, IL10, IL12, IL13, IL17, IL18, IL27, and IL33), only four variants, including TNF-α-rs1800629, TGF-β1-rs6957, IL13-rs1800925, and IL6-rs1800796, were associated with the risk of COPD development. This updated meta-analysis strongly supports the association of TNF-α-rs1800629, TGF-β1-rs6957, IL13-rs1800925, and IL6-rs1800796 variants with a high risk of COPD.
Topics: Humans; Polymorphism, Single Nucleotide; Transforming Growth Factor beta1; Tumor Necrosis Factor-alpha; Genetic Predisposition to Disease; Interleukin-13; Interleukin-6; Cytokines; Pulmonary Disease, Chronic Obstructive
PubMed: 37703677
DOI: 10.1016/j.cyto.2023.156352 -
Journal of Cerebral Blood Flow and... Nov 2018Investigation of genetic susceptibility to cerebrovascular disease has been of growing interest. A systematic review of human studies assessing neurogenomic aspects of...
Investigation of genetic susceptibility to cerebrovascular disease has been of growing interest. A systematic review of human studies assessing neurogenomic aspects of cerebrovascular disease was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Any association study exploring genetic variants located in the exome associated with one of the major cerebrovascular diseases with at least 500 subjects was eligible for inclusion. Of 6874 manuscripts identified, 35 studies met the inclusion criteria. Most studies of interest focused on ischemic stroke and cerebrovascular occlusive disease. Large cohort genetic association studies on hemorrhagic cerebrovascular disease were less common. In addition to rare, well-established monogenic conditions with significant risk for cerebrovascular disease, a number of genetic variants are also relevant to cerebrovascular pathogenesis as part of a multifactorial process. The 45 polymorphisms identified were located in genes involved in processes related to endothelial and vascular health (15 (33.4%) variants), plasma lipid metabolism (10 (22.2%) variants), inflammation (9 (20%) variants), coagulation (3 (6.7%) variants), and blood pressure modulation (2 (4.4%) variants), and other (6 (13.3%) variants). This work represents a comprehensive overview of genetic variants in the exome relevant to ischemic and hemorrhagic stroke pathophysiology.
Topics: Cerebrovascular Disorders; Genetic Predisposition to Disease; Humans
PubMed: 30182779
DOI: 10.1177/0271678X18797958 -
Medicina (Kaunas, Lithuania) Jul 2022: Starting in early December 2019, the novel Coronavirus Disease (COVID-19) from infection with COVID-19 has caused a global pandemic. Many aspects of its pathogenesis... (Review)
Review
: Starting in early December 2019, the novel Coronavirus Disease (COVID-19) from infection with COVID-19 has caused a global pandemic. Many aspects of its pathogenesis and related clinical consequences are still unclear. Early diagnosis and dynamic monitoring of prognostic factors are essential to improve the ability to manage COVID-19 infection. This study aimed to provide an account of the role played by vitamins C and D on the onset, progression and severity of COVID-19. Clinical features and infection-related risk factors are also briefly discussed. : In March 2022, the main online databases were accessed. All the articles that investigate the possible role of vitamins C and D on COVID-19 susceptibility, severity and progression were considered. : The current evidence on vitamin C and D supplementation in patients with COVID-19 infection is inconsistent and controversial. In some studies, vitamins were used as coadjuvant of a formal experimental therapy, while in others as main treatment. Ethnicity and hospital setting (inpatient/outpatient) were also variable. Moreover, there was no consensus between studies in administration protocol: high heterogeneity in dosage, administration, and duration of the treatment were evident. Finally, some studies administered vitamins pre- and/or during COVID infection, in patients with different risk factors and infection severity. : While waiting to develop a targeted, safe and effective therapy, it is important to investigate individual predisposition and proper disease management. Concluding, available data on the use of nutraceuticals in COVID-19 are inconsistent. However, there is a lack of evidence-based guidelines which recommend vitamin C and D supplementation in patients with COVID-19, and results from high quality randomised controlled trials (RCTs) are inconsistent. Current investigations so far are mostly observational, and include a relatively small sample size which can lead to biased results. Large-scale multicentre studies are therefore needed.
Topics: Ascorbic Acid; COVID-19; Disease Susceptibility; Humans; Pandemics; SARS-CoV-2; Vitamin D; Vitamins
PubMed: 35888660
DOI: 10.3390/medicina58070941 -
BMC Medical Genomics Sep 2019Pneumonia, sepsis, meningitis, and empyema due to Streptococcus pneumoniae is a major cause of morbidity and mortality. We provide a systemic overview of genetic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pneumonia, sepsis, meningitis, and empyema due to Streptococcus pneumoniae is a major cause of morbidity and mortality. We provide a systemic overview of genetic variants associated with susceptibility, phenotype and outcome of community acquired pneumococcal pneumonia (CAP) and invasive pneumococcal disease (IPD).
METHODS
We searched PubMed for studies on the influence of host genetics on susceptibility, phenotype, and outcome of CAP and IPD between Jan 1, 1983 and Jul 4, 2018. We listed methodological characteristics and when genetic data was available we calculated effect sizes. We used fixed or random effect models to calculate pooled effect sizes in the meta-analysis.
RESULTS
We identified 1219 studies of which 60 studies involving 15,358 patients were included. Twenty-five studies (42%) focused on susceptibility, 8 (13%) on outcome, 1 (2%) on disease phenotype, and 26 (43%) on multiple categories. We identified five studies with a hypothesis free approach of which one resulted in one genome wide significant association in a gene coding for lincRNA with pneumococcal disease susceptibility. We performed 17 meta-analyses of which two susceptibility polymorphisms had a significant overall effect size: variant alleles of MBL2 (odds ratio [OR] 1·67, 95% confidence interval [CI] 1·04-2·69) and a variant in CD14 (OR 1·77, 95% CI 1·18-2·66) and none of the outcome polymorphisms.
CONCLUSIONS
Studies have identified several host genetics factors influencing risk of pneumococcal disease, but many result in non-reproducible findings due to methodological limitations. Uniform case definitions and pooling of data is necessary to obtain more robust findings.
Topics: Disease Susceptibility; Humans; Lipopolysaccharide Receptors; Mannose-Binding Lectin; Odds Ratio; Phenotype; Pneumococcal Infections; Polymorphism, Genetic; RNA, Long Noncoding; Risk Factors
PubMed: 31519222
DOI: 10.1186/s12920-019-0572-x -
Inflammatory Bowel Diseases Jun 2012Inflammatory bowel diseases (IBD) result from an interaction between genetic and environmental factors. Preliminary findings suggest that susceptibility genes differ... (Review)
Review
BACKGROUND
Inflammatory bowel diseases (IBD) result from an interaction between genetic and environmental factors. Preliminary findings suggest that susceptibility genes differ between IBD patients in Asia and the West. We aimed to evaluate disease-predisposing genes in Asian IBD patients.
METHODS
A systematic review and meta-analysis were performed of published studies from 1950 to 2010 using keyword searches in MEDLINE, EMBASE, EBM Reviews, and BIOSIS Previews.
RESULTS
In all, 477 abstracts were identified and data extracted from 93 studies, comprising 17,976 IBD patients and 27,350 age- and sex-matched controls. Major nucleotide oligomerization domain (NOD)-2 variants in Western Crohn's disease (CD) patients were not associated with CD in Han Chinese, Japanese, South Korean, Indian, and Malaysian populations. New NOD2 mutations were, however, associated with CD in Malaysians (JW1), Han Chinese, and Indians (P268S). Autophagy-related protein 16-linked 1 (ATG16L1) was not associated with CD in East Asians (odds ratio [OR] 0.97; 95% confidence interval [CI] 0.84-1.13). Interleukin (IL)-23R was associated with CD in South Koreans (OR 1.8; 95% CI 1.16-2.82) and a single nucleotide polymorphism in IL-23R (Gly149Arg) was protective of CD in Han Chinese (OR 0.3; 95% CI 0.15-0.60). Tumor necrosis factor (TNF) superfamily gene-15 (SF15) polymorphisms were associated with CD (OR 2.68; 95% CI 1.86-3.86), while TNF-308 polymorphisms (OR 1.82; 95% CI 1.15-2.9), cytotoxic T lymphocyte antigen (CTLA)-4 (OR 2.75; 95% CI 1.22-6.22) and MICA allele (OR 2.41; 95% CI 1.89-3.07) were associated with ulcerative colitis in Asians.
CONCLUSIONS
Genetic mutations of IBD in Asians differ from Caucasians. New mutations and susceptibility genes identified in Asian IBD patients provide an opportunity to explore new disease-associated mechanisms in this population of rising incidence.
Topics: Asian People; Genetic Predisposition to Disease; Humans; Inflammatory Bowel Diseases; Meta-Analysis as Topic
PubMed: 21887729
DOI: 10.1002/ibd.21845