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EBioMedicine Mar 2023Mass vaccination has dramatically reduced the incidence of severe COVID-19, with most cases now presenting as self-limiting upper respiratory tract infections. However,...
BACKGROUND
Mass vaccination has dramatically reduced the incidence of severe COVID-19, with most cases now presenting as self-limiting upper respiratory tract infections. However, those with co-morbidities, the elderly and immunocompromised, as well as the unvaccinated, remain disproportionately vulnerable to severe COVID-19 and its sequelae. Furthermore, as the effectiveness of vaccination wanes with time, immune escape SARS-CoV-2 variants could emerge to cause severe COVID-19. Reliable prognostic biomarkers for severe disease could be used as early indicator of re-emergence of severe COVID-19 as well as for triaging of patients for antiviral therapy.
METHODS
We performed a systematic review and re-analysis of 7 publicly available datasets, analysing a total of 140 severe and 181 mild COVID-19 patients, to determine the most consistent differentially regulated genes in peripheral blood of severe COVID-19 patients. In addition, we included an independent cohort where blood transcriptomics of COVID-19 patients were prospectively and longitudinally monitored previously, to track the time in which these gene expression changes occur before nadir of respiratory function. Single cell RNA-sequencing of peripheral blood mononuclear cells from publicly available datasets was then used to determine the immune cell subsets involved.
FINDINGS
The most consistent differentially regulated genes in peripheral blood of severe COVID-19 patients were MCEMP1, HLA-DRA and ETS1 across the 7 transcriptomics datasets. Moreover, we found significantly heightened MCEMP1 and reduced HLA-DRA expression as early as four days before the nadir of respiratory function, and the differential expression of MCEMP1 and HLA-DRA occurred predominantly in CD14+ cells. The online platform which we developed is publicly available at https://kuanrongchan-covid19-severity-app-t7l38g.streamlitapp.com/, for users to query gene expression differences between severe and mild COVID-19 patients in these datasets.
INTERPRETATION
Elevated MCEMP1 and reduced HLA-DRA gene expression in CD14+ cells during the early phase of disease are prognostic of severe COVID-19.
FUNDING
K.R.C is funded by the National Medical Research Council (NMRC) of Singapore under the Open Fund Individual Research Grant (MOH-000610). E.E.O. is funded by the NMRC Senior Clinician-Scientist Award (MOH-000135-00). J.G.H.L. is funded by the NMRC under the Clinician-Scientist Award (NMRC/CSAINV/013/2016-01). S.K. is funded by the NMRC under the Transition Award. This study was sponsored in part by a generous gift from The Hour Glass.
Topics: Humans; Aged; HLA-DR alpha-Chains; COVID-19; SARS-CoV-2; Leukocytes, Mononuclear; Prognosis
PubMed: 36801619
DOI: 10.1016/j.ebiom.2023.104472 -
Transplant Immunology Dec 2023Kidney transplantation is considered an ideal treatment for end-stage renal disease (ESRD) because it provides a longer and better quality of life than dialysis.... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Kidney transplantation is considered an ideal treatment for end-stage renal disease (ESRD) because it provides a longer and better quality of life than dialysis. ABO-incompatible (ABO-I) kidney transplantation relies on two principles: (i) removal of antibodies from a blood group; and (ii) inhibition of reappearance of blood group antibodies by intensifying the induction and maintenance of immunosuppression. This systematic review aimed to analyze the success and safety of ABO-I live-donor kidney transplantation.
METHODS
Databases, including Google Scholar, PubMed, Embase, Web of Science, and Medline were searched. Search duration was from the database establishment to December 2022. A thorough search was performed for relevant studies investigating the success and safety of ABO-I live-donor kidney transplantation. Two investigators independently extracted literature information and assessed the quality of the included studies. Heterogeneity test was performed using Cochrane's Q and chi-squared tests. All statistical analyses were performed using R software (version 4.2.1).
RESULTS
The search for relevant literature in the five electronic databases yielded 1238 articles. Of the 1238 articles, only 15 were included. Meta-analysis of outcomes from five studies showed a survival rate of 0.93 (95% confidence interval [CI]: 0.88 to 0.97, P < 0.001) after ≥3 years, while outcomes from 12 studies revealed a short-term patient survival rate of 0.94 (95% CI: 0.92 to 0.96, P = 0.75). In contrast, long- and short-term graft survival rates were 0.89 (95% CI: 0.75 to 0.96, P < 0.001) and 0.94 (95% CI: 0.90 to 0.97, P < 0.001), respectively. Incidence rates of infectious, surgical, and medical complications were 0.31 (95% CI: 0.22 to 0.41, P < 0.001), 0.12 (95% CI: 0.05 to 0.25, P < 0.001), and 0.38 (95% CI: 0.17 to 0.66, P < 0.001), respectively.
CONCLUSION
Good long- and short-term patient outcomes and graft survival rates were observed after ABO-I kidney transplantation. Similarly, the safety of performing kidney transplantations from living donors with ABO-I blood groups was established by the results of the current meta-analysis. Therefore, ABO-I live-donor kidney transplantations should be encouraged to reduce the time recipients spend on waiting lists and supplement the existing paired-exchange donor program.
Topics: Humans; Kidney Transplantation; ABO Blood-Group System; Living Donors; Quality of Life; Renal Dialysis; Blood Group Incompatibility; Antibodies; Graft Survival; Graft Rejection
PubMed: 37648033
DOI: 10.1016/j.trim.2023.101921 -
Journal of Hepatology Nov 2011Previous studies examining the relationship between the C282Y and H63D HFE mutations and presence of nonalcoholic fatty liver disease (NAFLD) have yielded conflicting... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
Previous studies examining the relationship between the C282Y and H63D HFE mutations and presence of nonalcoholic fatty liver disease (NAFLD) have yielded conflicting results. The goal of this study was to systematically evaluate and summarize data on the association between these two variants and the presence of NAFLD.
METHODS
The authors searched EMBASE and PUBMED from August 1, 1996 to August 12, 2010. Two investigators independently conducted data abstraction. Ethnic specific weighted prevalence was calculated and pooled odds ratios were estimated using the random effects model.
RESULTS
From 2542 references, the authors included 16 case-control studies and 14 case-only studies, or 2610 cases and 7298 controls. The majority of the studies came from Caucasian populations (2287 cases and 4275 controls). The weighted prevalence of HFE mutations in cases was comparable to controls. The meta-analysis was restricted to Caucasians only because of the small sample size of non Caucasian participants. The pooled odds ratio for the presence of any HFE genetic variant in cases was 1.03 (95%CI: 0.90, 1.17; I(2): 65.8%, 95%CI: 38.5, 81.0). The presence of other genotypes and secondary analyses yielded similar non significant findings.
CONCLUSIONS
Our systematic review does not support an association between the HFE genetic variants and the presence of NAFLD.
Topics: Fatty Liver; Genotype; Hemochromatosis Protein; Histocompatibility Antigens Class I; Humans; Membrane Proteins; Mutation; Non-alcoholic Fatty Liver Disease; White People
PubMed: 21354231
DOI: 10.1016/j.jhep.2011.02.013 -
Seizure Nov 2022Antiepileptic drugs (AEDs) are extensively used to manage epilepsy and other comorbidities associated with seizures. Human Leukocyte Antigen (HLA) has a strong... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Antiepileptic drugs (AEDs) are extensively used to manage epilepsy and other comorbidities associated with seizures. Human Leukocyte Antigen (HLA) has a strong association with AED-induced severe cutaneous adverse drug reactions.
OBJECTIVE
We aimed to perform a systematic review and meta-analysis to identify, critically evaluate, and synthesize the best possible evidence on HLA-associated AED-induced Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis (SJS/TEN).
METHODS
MEDLINE/PubMed, Scopus, and the Cochrane Library were searched for literature from inception up to July 2022. We included case control studies analyzing association between HLA and AED-induced SJS/TEN. We assessed the studies' risk of bias in using Quality of genetic studies (Q-genie) tool. Outcomes focused on association (risk) between HLA and AED-induced SJS/TEN. The estimated risk was presented in the form of odds ratio (OR).
RESULTS
We included 37 studies (51,422 participants; 7027 cases and 44,395 controls). There was a significantly higher risk of Carbamazepine-induced SJS/TEN with HLA-A (OR: 1.50; 95% CI: 1.03 to 2.17), HLA-B (OR: 1.94; 95% CI: 1.45 to 2.58), HLA-C (OR: 7.83; 95% CI: 4.72 to 12.98), and HLA-DRB1 (OR: 2.82; 95% CI: 1.94 to 4.12). Lamotrigine-induced SJS/TEN posed a higher risk with HLA-A (OR: 2.38; 95% CI: 1.26 to 4.46) and HLA-B (OR: 2.79; 95% CI: 1.75 to 4.46). Phenytoin-induced SJS/TEN showed a higher risk with HLA-A (OR: 3.47; 95% CI: 2.17 to 5.56), HLA-B (OR: 1.72; 95% CI: 1.38 to 2.15), and HLA-C (OR: 2.92; 95% CI: 1.77 to 4.83). Phenobarbital-induced SJS/TEN had a higher risk with HLA-A (OR: 6.98; 95% CI: 1.81 to 26.84), HLA-B (OR: 2.40; 95% CI: 1.39 to 4.17), and HLA-C (OR: 3.37; 95% CI: 1.03 to 11.01). Zonisamide-induced SJS/TEN was significantly associated with HLA-A*02:07 (OR: 9.77; 95% CI: 3.07 to 31.1), HLA-B*46:01 (OR: 6.73; 95% CI: 2.12 to 21.36), and HLA-DRB1×08:03 (OR: 3.78; 95% CI: 1.20 to 11.97). All other alleles of HLA were observed to have a non-significant association with AED-induced SJS/TEN. All included studies were of good quality, with a score of >50 and a mean score of 54.96 out of 77.
CONCLUSION
Our study showed a significant association between few variants of HLA alleles and AED-induced SJS/TEN. Evidences from our study could help in population-based studies and in implementation of individualized treatment regimens. These findings could be part of translational research helping in precision therapy.
Topics: Humans; Stevens-Johnson Syndrome; HLA-DRB1 Chains; HLA-C Antigens; Asian People; HLA-B Antigens; Anticonvulsants; HLA Antigens
PubMed: 36183454
DOI: 10.1016/j.seizure.2022.09.011 -
BMC Musculoskeletal Disorders Jun 2017Axial spondyloarthritis (AxSpA) is a relatively frequent and debilitating disease, with a prevalence ranging from 0.1 to 2% in the Caucasian population. Current... (Review)
Review
BACKGROUND
Axial spondyloarthritis (AxSpA) is a relatively frequent and debilitating disease, with a prevalence ranging from 0.1 to 2% in the Caucasian population. Current Assessment of Spondyloarthritis International Society (ASAS) classification criteria of AxSpA rely either on sacroiliitis on imaging plus one SpA feature or positive HLAB27 antigen plus two SpA features, in a patient with chronic low back pain and age at onset of less than 45 years. Therefore, HLA-B27 is a central feature in SpA classification and plays a pivotal role in referral strategies and early diagnosis. The primary objective of the study is to review the prevalence of HLA-B27 in normal and AxSpA populations in Middle Eastern and Arab Countries and to assess the strength of association between HLA-B27 antigen and AxSpA. The secondary objective is to identify the gaps in the methodology of the studies and suggest a framework for future research.
METHODS
Studies were included in the analysis if they reported prevalence of HLA-B27 in AxSpA and/or general population and if they covered geographical location in the Middle East or Arab countries in the Mediterranean basin. Odds ratios (OR) were calculated for each country, as a measure of the strength of association between HLA-B27 and AxSpA, compared to the normal population, using the two-by-two frequency table. Available data from the literature were analyzed according to the following quality indicators: sample size, method of HLA-B27 testing, presence of control group and external validity.
RESULTS
Twenty-seven studies were analyzed. HLAB27 prevalence in the normal population ranged from 0.3% (Oman) to 6.8% (Turkey). HLA-B27 prevalence in AxSpA ranged from 26.2% (Lebanon) to 91% (Turkey). HLA-B27 prevalence in all SpA ranged from 13.87% (Lebanon) to 69.43% (Kuwait). Peripheral SpA was less associated with HLA-B27 than AxSpA, indicating the need of differentiating between the two entities when calculating prevalence. When available (8 studies), the OR ranged from 21.63 (Morocco) to 105.6 (Syria). The high heterogeneity between the results can be due to differences in methodology: study sample size, different classification criteria, absence of control groups, HLA-B27 testing method.
CONCLUSIONS
The prevalence of HLA-B27 in the normal population is significantly lower in the Middle Eastern and Arab countries than in Western Countries. However, HLA-B27 testing can be useful for AxSpA positive diagnosis, given the high OR. Heterogeneity between countries may be due to methodological differences.
Topics: HLA-B27 Antigen; Humans; Middle East; Spondylarthritis
PubMed: 28662723
DOI: 10.1186/s12891-017-1639-5 -
American Journal of Obstetrics and... Aug 2022This study investigated the efficacy and safety of pharmacologic interventions to prevent vertical transmission of the hepatitis B virus. (Meta-Analysis)
Meta-Analysis Review
Comparative efficacy and safety of pharmacologic interventions to prevent mother-to-child transmission of hepatitis B virus: a systematic review and network meta-analysis.
OBJECTIVE
This study investigated the efficacy and safety of pharmacologic interventions to prevent vertical transmission of the hepatitis B virus.
DATA SOURCES
Medline, Cochrane, and Scopus databases were searched up to October 28, 2020.
STUDY ELIGIBILITY CRITERIA
All randomized controlled trials reporting vertical hepatitis B virus transmission with pharmacologic intervention were included.
METHODS
Risk of bias was assessed using the Cochrane Risk-of-Bias tool, version 2. Treatment efficacy was estimated using stratified network meta-analysis on the basis of maternal hepatitis B envelope antigen status.
RESULTS
Nineteen studies were included for mothers positive for hepatitis B surface and envelope antigens. Pooling indicated that a combination of hepatitis B vaccination and hepatitis B immunoglobulin in infants significantly reduced transmission risk compared with vaccination alone, with a risk ratio of 0.52 (95% confidence interval; 0.30-0.91). Only the addition of maternal tenofovir disoproxil fumarate, but not telbivudine, lamivudine, or maternal hepatitis B immunoglobulin further reduced transmission risk compared with a combination of hepatitis B vaccination and hepatitis B immunoglobulin in infants, with a pooled risk ratio of 0.10 (0.03-0.35). Twelve studies conducted in mothers with hepatitis B surface antigen positivity and mixed, unknown, or negative hepatitis B envelope antigen status provided limited evidence to suggest that maternal hepatitis B immunoglobulin combined with hepatitis B vaccination and immunoglobulin in infants was the likely best treatment, but this failed to reach statistical significance compared with a combination of hepatitis B vaccination and immunoglobulin in infants. Similarly, infant hepatitis B immunoglobulin, added to vaccination, likely provides additional benefit but failed to reach statistical significance.
CONCLUSION
A combination of hepatitis B vaccination and immunoglobulin in infants is the cornerstone for prevention of vertical transmission for mothers positive for both hepatitis B surface and envelope antigens. The addition of maternal tenofovir to this infant combination regimen was considered the likely most effective treatment. For infants of mothers with hepatitis B surface antigen positivity and mixed, unknown, or negative hepatitis B envelop antigen status, no additional agents provided further benefit beyond hepatitis B vaccination alone.
Topics: Antiviral Agents; Female; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B virus; Humans; Immunoglobulins; Infant; Infectious Disease Transmission, Vertical; Network Meta-Analysis; Pregnancy; Pregnancy Complications, Infectious; Tenofovir; Viral Load
PubMed: 35263648
DOI: 10.1016/j.ajog.2022.02.042 -
PloS One 2013Until recently, celiac disease was considered to be rare in China. We aimed to estimate its true status. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Until recently, celiac disease was considered to be rare in China. We aimed to estimate its true status.
METHODS
By searching the MEDLINE database and four Chinese full-text databases (CNKI, CBM, VIP and WANFANG) (up to August 2012), as well as two HLA allele frequency net databases and the Chinese Statistics Yearbook databases, we systematically reviewed the literature on definite and suspected cases of celiac disease, the predisposing HLA allele frequencies, and on gluten exposure in China. Meta-analysis was performed by analyzing DQ2, DQ8 and DQB1*0201 gene frequencies and heterogeneity in populations from different geographic regions and ethnicities in China.
RESULTS
At present, the number of reported celiac disease cases is extremely low in China. The frequencies of the HLA-DQ2.5 and HLA-DQ8 haplotypes were 3.4% (95% confidence interval 1.3-5.5%) and 2.1% (0.1-4.1%), respectively. HLA-DQ2 and HLA-DQ8 antigen frequencies were 18.4% (15.0-21.7%) and 8.0% (4.5-11.4%), respectively. The frequency of the DQB1*0201 allele was 10.5% (9.3-11.6%) and it was more common in the northern Chinese than in the southern Chinese populations. The chance of being exposed to gluten is rapidly increasing all over China nowadays.
CONCLUSION
The data on HLA haplotyping, in conjunction with increasing wheat consumption, strongly suggests that the occurrence of celiac disease is more common in China than currently reported. Coordinated measures by the Chinese government, medical and agricultural research institutions, and food industries, would be justified to create more awareness about celiac disease and to prevent it becoming a medical and societal burden.
Topics: Alleles; Celiac Disease; China; Databases, Bibliographic; Gene Expression; Gene Frequency; Genetic Heterogeneity; Glutens; HLA-DQ Antigens; HLA-DQ beta-Chains; Haplotypes; Histocompatibility Testing; Humans; Incidence
PubMed: 24324669
DOI: 10.1371/journal.pone.0081151 -
Frontiers in Immunology 2023Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Several studies have investigated the impact of circulating complement-activating anti-human leukocyte antigen donor-specific antibodies (anti-HLA DSAs) on organ transplant outcomes. However, a critical appraisal of these studies and a demonstration of the prognostic value of complement-activating status over anti-HLA DSA mean fluorescence intensity (MFI) level are lacking.
METHODS
We conducted a systematic review, meta-analysis and critical appraisal evaluating the role of complement-activating anti-HLA DSAs on allograft outcomes in different solid organ transplants. We included studies through Medline, Cochrane, Scopus, and Embase since inception of databases till May 05, 2023. We evaluated allograft loss as the primary outcome, and allograft rejection as the secondary outcome. We used the Newcastle-Ottawa Scale and funnel plots to assess risk of bias and used bias adjustment methods when appropriate. We performed multiple subgroup analyses to account for sources of heterogeneity and studied the added value of complement assays over anti-HLA DSA MFI level.
RESULTS
In total, 52 studies were included in the final meta-analysis (11,035 patients). Complement-activating anti-HLA DSAs were associated with an increased risk of allograft loss (HR 2.77; 95% CI 2.33-3.29, p<0.001; I²=46.2%), and allograft rejection (HR 4.98; 95% CI 2.96-8.36, p<0.01; I²=70.9%). These results remained significant after adjustment for potential sources of bias and across multiple subgroup analyses. After adjusting on pan-IgG anti-HLA DSA defined by the MFI levels, complement-activating anti-HLA DSAs were significantly and independently associated with an increased risk of allograft loss.
DISCUSSION
We demonstrated in this systematic review, meta-analysis and critical appraisal the significant deleterious impact and the independent prognostic value of circulating complement-activating anti-HLA DSAs on solid organ transplant risk of allograft loss and rejection.
Topics: Humans; Graft Rejection; Organ Transplantation; Complement System Proteins; Transplantation, Homologous; HLA Antigens
PubMed: 37849755
DOI: 10.3389/fimmu.2023.1265796 -
Frontiers in Immunology 2023PD-1/PD-L1 immune checkpoint inhibitors (ICIs) have been controversial in the treatment of metastatic triple negative breast cancer (mTNBC). We collected randomized... (Meta-Analysis)
Meta-Analysis
BACKGROUND
PD-1/PD-L1 immune checkpoint inhibitors (ICIs) have been controversial in the treatment of metastatic triple negative breast cancer (mTNBC). We collected randomized controlled trials in accordance with the study and carried out meta-analysis to comprehensively evaluate the efficacy and safety of immune checkpoint inhibitors in mTNBC.
AIM
To systematically evaluate the efficacy and safety of PD-1/PD-L1 ICIs (hereinafter referred to as ICIs) in the treatment of mTNBC.
METHODS
As of 2023.2.5, Medline, PubMed, Embase, Cochrane library database and Web of Science were searched to determine the study in accordance with the trial of ICIs in the treatment of mTNBC. The assessment endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety. Meta-analysis of the included studies was performed using Revman 5.4.
RESULTS
A total of six trials with 3172 patients were included in this meta-analysis. The ORR of ICIs combined with chemotherapy was significantly improved compared with chemotherapy (HR=0.88, 95%CI: 0.81-0.94, I= 0%). For PFS, the experimental group were better than the control group in both intention-to-treat (ITT) population and PD-L1 positive population, showing statistical significance (ITT: HR=0.81, 95%CI: 0.74-0.89, P<0.05, I= 0%; PD-L1 positive: HR=0.72, 95%CI: 0.63-0.82, P<0.05, I= 18%); For OS, in the ITT population, no statistical difference was observed in either ICIs combined with chemotherapy(HR=0.92, 95%CI: 0.83-1.02, P=0.10)or immune monotherapy(HR=0.78, 95%CI: 0.44-1.36, P=0.37), in the PD-L1 positive population, ICIs group had better OS than chemotherapy group (HR=0.83, 95%CI: 0.74-0.93, P < 0.05); In safety, serious adverse event (SAE) was no statistically significant difference between the ICIs group and the chemotherapy group; however, the incidence of immune-related adverse event (irAE) was significantly higher in the ICIs group than in the chemotherapy group (HR=2.15, 95%CI: 1.45-3.19, P < 0.05).
CONCLUSION
ICIs combined with chemotherapy significantly improved the PFS of mTNBC, however, ICIs only improved the OS in PD-L1 positive people, and no statistical difference was observed in ITT population; while benefiting from ICIs, we found that irAE in ICIs group increased significantly, and its high rate of adverse events still needs to be taken seriously.
Topics: Humans; Immune Checkpoint Inhibitors; Programmed Cell Death 1 Receptor; Triple Negative Breast Neoplasms; B7-H1 Antigen; Control Groups
PubMed: 37377959
DOI: 10.3389/fimmu.2023.1206689 -
Jornal de Pediatria 2023Fecal calprotectin is an inflammatory marker used for monitoring intestinal diseases. It has been studied as a marker of intestinal inflammation in cystic fibrosis (CF),... (Review)
Review
OBJECTIVES
Fecal calprotectin is an inflammatory marker used for monitoring intestinal diseases. It has been studied as a marker of intestinal inflammation in cystic fibrosis (CF), a multi-systemic genetic disease caused by alterations to the CFTR gene. Manifestations of the disease favor a systemic inflammation not limited to the respiratory tract, therefore, calprotectin is a non-invasive and effective diagnostic method. The aim of the study was to perform a systematic review of the literature with a qualitative synthesis of studies.
SOURCES
The articles were selected from PubMed, Web of Science, Scielo and Lilacs.
SUMMARY OF THE FINDINGS
Nine studies were selected for that qualitative synthesis, one was a randomized clinical trial, and eight were case-control or cohort designs. Most studies have indicated that calprotectin is a marker of systemic inflammation in CF and not just intestinal inflammation. Calprotectin is an aid in monitoring inflammatory bowel conditions in patients with cystic fibrosis.
CONCLUSION
Further studies should be conducted to investigate the role of this marker in the systemic inflammation of CF.
Topics: Humans; Cystic Fibrosis; Leukocyte L1 Antigen Complex; Biomarkers; Inflammation; Intestines; Feces; Randomized Controlled Trials as Topic
PubMed: 35523321
DOI: 10.1016/j.jped.2022.01.006