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Vox Sanguinis Nov 2022Sickle cell disease (SCD) patients are commonly treated with red blood cell (RBC) transfusion. Pretransfusion tests commonly involve limited serological antibody... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND OBJECTIVES
Sickle cell disease (SCD) patients are commonly treated with red blood cell (RBC) transfusion. Pretransfusion tests commonly involve limited serological antibody testing. RBC alloimmunization to RBC antigens is a frequently encountered complication seen in chronically transfused patients. Genetic factors such as the human leukocyte antigen (HLA) are known to influence and regulate immune responses. HLAs are highly polymorphic and play an essential role in regulating immune responses, including RBC alloimmunization. The aim of this study was to conduct a systematic review and meta-analysis to evaluate the association between HLA Class II allelic polymorphisms with the possible risk of developing RBC alloantibodies.
MATERIALS AND METHODS
Four databases were systematically searched for relevant studies between the years 2000 and 2021 following the PRISMA guidelines. Four articles met the eligibility and quality criterion, and three alleles, HLA-DRB1*04, HLA-DRB1*15 and HLA-DQB1*03, that were found to be potentially associated with an increased risk in alloantibody formation were included.
RESULTS
The primary outcome measure was alloimmunization by RBC antigen exposure in multiply transfused SCD patients. The total estimate of alloimmunization of the SCD patients was 2.33 (95% CI, 1.58-3.44), demonstrating susceptibility to RBC alloantibody formation. Heterogeneity between the studies was insignificant, suggesting the differences associated with random sampling errors. The results showed that SCD patients carry an increased risk of producing RBC alloantibodies.
CONCLUSION
A strategy to prevent RBC alloimmunization is genotyping for genetically susceptible SCD patients receiving multiple transfusions. Early identification of genetic variants that can potentially increase the risk of RBC alloimmunization could aid in the screening process and selection of phenotypically matched RBC units.
Topics: Humans; Isoantibodies; Anemia, Sickle Cell; Erythrocytes; Erythrocyte Transfusion; Anemia, Hemolytic, Autoimmune; Immunity
PubMed: 36102140
DOI: 10.1111/vox.13351 -
Journal of Orthopaedic Translation Mar 2020Although emerging studies have provided evidence that osteocytes are actively involved in fracture healing, there is a general lack of a detailed understanding of the... (Review)
Review
BACKGROUND
Although emerging studies have provided evidence that osteocytes are actively involved in fracture healing, there is a general lack of a detailed understanding of the mechanistic pathway, cellular events and expression of markers at different phases of healing.
METHODS
This systematic review describes the role of osteocytes in fracture healing from early to late phase. Literature search was performed in PubMed and Embase. Original animal and clinical studies with available English full-text were included. Information was retrieved from the selected studies.
RESULTS
A total of 23 articles were selected in this systematic review. Most of the studies investigated changes of various genes and proteins expression patterns related to osteocytes. Several studies have described a constant expression of osteocyte-specific marker genes throughout the fracture healing cascade followed by decline phase with the progress of healing, denoting the important physiological role of the osteocyte and the osteocyte lacuno-canalicular network in fracture healing. The reports of various markers suggested that osteocytes could trigger coordinated bone healing responses from cell death and expression of proinflammatory markers cyclooxygenase-2 and interleukin 6 at early phase of fracture healing. This is followed by the expression of growth factors bone morphogenetic protein-2 and cysteine-rich angiogenic inducer 61 that matched with the neo-angiogenesis, chondrogenesis and callus formation during the intermediate phase. Tightly controlled regulation of osteocyte-specific markers E11/Podoplanin (E11), dentin matrix protein 1 and sclerostin modulate and promote osteogenesis, mineralisation and remodelling across different phases of fracture healing. Stabilised fixation was associated with the finding of higher number of osteocytes with little detectable bone morphogenetic proteins expressions in osteocytes. Sclerostin-antibody treatment was found to result in improvement in bone mass, bone strength and mineralisation.
CONCLUSION
To further illustrate the function of osteocytes, additional longitudinal studies with appropriate clinically relevant model to study osteoporotic fractures are crucial. Future investigations on the morphological changes of osteocyte lacuno-canalicular network during healing, osteocyte-mediated signalling molecules in the transforming growth factor-beta-Smad3 pathway, perilacunar remodelling, type of fixation and putative biomarkers to monitor fracture healing are highly desirable to bridge the current gaps of knowledge.The translational potential of this article: This systematic review provides an up-to-date chronological overview and highlights the osteocyte-regulated events at gene, protein, cellular and tissue levels throughout the fracture healing cascade, with the hope of informing and developing potential new therapeutic strategies that could improve the timing and quality of fracture healing in the future.
PubMed: 32309136
DOI: 10.1016/j.jot.2019.07.005 -
Expert Review of Vaccines 2024This review aimed to systematically evaluate the immunogenicity and safety of the candidate Ebola virus vaccine (EVV). (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
This review aimed to systematically evaluate the immunogenicity and safety of the candidate Ebola virus vaccine (EVV).
METHODS
We searched five databases for randomized controlled trials (RCTs) evaluating the effects of EVV on healthy adults. The primary outcomes were relative risk (RR) of sero-conversion or sero-response of EVV in healthy adults between the groups that received EVV and the controls.
RESULTS
Twenty-nine RCTs ( = 23573) were included. There was a significant difference in RR of sero-conversion of EVV (RR 13.18; 95% CI 11.28-15.41; I = 33%; < 0.01) between the two groups. There was a significant difference in RR of adverse events (AEs) of EVV (RR 1.49; 95% CI 1.27-1.74; I = 88%; < 0.01), although no difference in RR of serious AE (SAE) between the two groups. Subgroup analysis showed that there was no significant difference in RR of AEs for DNAEBO, EBOV-GP, MVA, and rVSVN4CT1 vaccines, compared with controls.
CONCLUSIONS
The DNAEBO, EBOV-GP, MVA, and rVSVN4CT1 vaccines are likely to be safe and immunogenic, tending to support the vaccination against Ebola disease. These findings should provide much-needed evidence for public health policy makers to develop preventive measures based on disease prevalence features and socio-economic conditions.
Topics: Adult; Humans; Ebola Vaccines; Randomized Controlled Trials as Topic; Hemorrhagic Fever, Ebola; Vaccination; Antibody Formation; Ebolavirus
PubMed: 38112249
DOI: 10.1080/14760584.2023.2296937 -
Journal of Pharmacy & Bioallied Sciences Jul 2023Multiple myeloma is a malignant cancerous condition that is characterized by abnormal plasma cell production and can lead to bone destruction due to increased...
Multiple myeloma is a malignant cancerous condition that is characterized by abnormal plasma cell production and can lead to bone destruction due to increased osteoclastic activity and decreased osteoblastic activity. Many therapeutic therapies are used to treat diseases, such as chemotherapy and radiotherapy. In recent years, anti-sclerostin antibody treatment has been under investigation for its effect on the multiple myeloma. The present study was conducted to assess the effective therapeutic use of anti-sclerostin antibody in the treatment of multiple myeloma. The literature search was conducted using PubMed, Google Scholar, ScienceDirect, and PubMed Central using the following MeSH terms: "multiple myeloma", "anti-sclerostin antibody", "ubiquitin-proteasome pathway", "proteasome inhibitor", "Wnt pathway". A total of 348 articles were screened. Twenty-five out of 348 were full-text articles assessed for eligibility, and four articles were used in this systematic review. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used for the reporting of this systematic review. A total of four randomized control trials (RCT) were included and used in this systematic review. The anti-sclerostin antibodies were various other drugs, and it was found that the anti-sclerostin antibody was effective in preventing autoantibody formation, decreasing bone destruction, and increasing trabecular bone. Anti-sclerostin antibody was found to be effective in decreasing bone destruction by reducing osteoclastic activity and increasing osteoblastic activity associated with multiple myeloma.
PubMed: 37654355
DOI: 10.4103/jpbs.jpbs_560_22 -
Journal of Plastic, Reconstructive &... Sep 2020Vascularised composite allotransplantation (VCA) permits like-for-like reconstruction following extensive soft tissue injuries. The initial management of extensive soft...
INTRODUCTION
Vascularised composite allotransplantation (VCA) permits like-for-like reconstruction following extensive soft tissue injuries. The initial management of extensive soft tissue injury can lead to the development of anti-HLA antibodies through injury-related factors, transfusion and cadaveric grafting. The role of antibody-mediated rejection, donor-specific antibody formation and graft rejection in the context of VCA remains unclear. This systematic review aimed to determine whether pre-transplant management strategies influence immunological outcome following VCA.
METHODS
A systematic review of MEDLINE, EMBASE and CINAHL using a PRISMA-compliant methodology up to February 2019 was conducted. Pre-transplant, procedural and long-term outcome data were collected and recorded for all VCA recipients on an individual patient basis.
RESULTS
The search revealed 3,847 records of which 114 met inclusion criteria and reported clinical data related to 100 patients who underwent 129 VCA transplants. Trauma (50%) and burns (15%) were the most frequent indications for VCA. Of all 114 studies, only one reported acute resuscitative management. Fifteen patients were sensitised prior to reconstructive transplantation with an 80%%incidence of acute rejection in the first post-operative year. Seven patients demonstrated graft vasculopathy, only one of whom had demonstrated panel reactive antibodies.
CONCLUSIONS
Currently employed acute management strategies may predispose to the development of anti-HLA antibodies, adding to the already complex immunological challenge of VCA. To determine whether association between pre-transplant management and outcomes exists, further refinement of international registries is required.
Topics: Burns; Graft Rejection; HLA Antigens; Humans; Immune Tolerance; Soft Tissue Injuries; Surgical Wound Infection; Vascularized Composite Allotransplantation
PubMed: 32475735
DOI: 10.1016/j.bjps.2020.05.010 -
Medical Microbiology and Immunology Aug 2019Latent infection with cytomegalovirus (CMV) is thought to accelerate aging of the immune system. With age, influenza vaccine responses are impaired. Although several... (Meta-Analysis)
Meta-Analysis
Latent infection with cytomegalovirus (CMV) is thought to accelerate aging of the immune system. With age, influenza vaccine responses are impaired. Although several studies investigated the effect of CMV infection on antibody responses to influenza vaccination, this led to contradicting conclusions. Therefore, we investigated the relation between CMV infection and the antibody response to influenza vaccination by performing a systematic review and meta-analysis. All studies on the antibody response to influenza vaccination in association with CMV infection were included (n = 17). The following outcome variables were extracted: (a) the geometric mean titer pre-/post-vaccination ratio (GMR) per CMV serostatus group, and in addition (b) the percentage of subjects with a response per CMV serostatus group and (c) the association between influenza- and CMV-specific antibody titers. The influenza-specific GMR revealed no clear evidence for an effect of CMV seropositivity on the influenza vaccine response in young or old individuals. Meta-analysis of the response rate to influenza vaccination showed a non-significant trend towards a negative effect of CMV seropositivity. However, funnel plot analysis suggests that this is a consequence of publication bias. A weak negative association between CMV antibody titers and influenza antibody titers was reported in several studies, but associations could not be analyzed systematically due to the variety of outcome variables. In conclusion, by systematically integrating the available studies, we show that there is no unequivocal evidence that latent CMV infection affects the influenza antibody response to vaccination. Further studies, including the level of CMV antibodies, are required to settle on the potential influence of latent CMV infection on the influenza vaccine response.
Topics: Antibodies, Viral; Antibody Formation; Cytomegalovirus; Cytomegalovirus Infections; Humans; Immunosenescence; Influenza Vaccines; Orthomyxoviridae; Virus Latency
PubMed: 30949763
DOI: 10.1007/s00430-019-00602-z -
Diabetes & Metabolic Syndrome Feb 2022DM patients' antibody response after the COVID-19 vaccine is still unknown amid the COVID-19 vaccination rollout. This study aimed to explore the SARS-CoV-2 antibody...
BACKGROUND AND AIM
DM patients' antibody response after the COVID-19 vaccine is still unknown amid the COVID-19 vaccination rollout. This study aimed to explore the SARS-CoV-2 antibody response or seropositivity among DM patients following the COVID-19 vaccine administration.
METHODS
We performed a systematic review of the literature consisting of observational or cross-sectional studies, which reported the antibody serology or seropositivity among DM patients by following the PRISMA 2020 guidelines.
RESULTS
Eight studies with a total of 64468 patients were identified, and 5156 (7.9%) of them had diabetes. Most studies showed that antibody response and seropositivity in DM patients were lower than healthy population after one until four weeks following full COVID-19 vaccination dose.
CONCLUSION
The antibody response and seropositivity after the COVID-19 vaccine in DM patients were lower than in healthy subjects. Therefore, DM patients are expected to receive vaccines according to the dose and schedule appropriately and might be prioritized to receive vaccine boosters.
Topics: Antibodies, Viral; Antibody Formation; BNT162 Vaccine; COVID-19; COVID-19 Vaccines; Diabetes Mellitus, Type 2; SARS-CoV-2; Vaccination
PubMed: 35104750
DOI: 10.1016/j.dsx.2022.102406 -
Experimental and Clinical... Jan 2022Kidney allograft failure is a significant complication in kidney transplant recipients, and the surgical decision to perform allograft nephrectomy poses a strong dilemma... (Review)
Review
Kidney allograft failure is a significant complication in kidney transplant recipients, and the surgical decision to perform allograft nephrectomy poses a strong dilemma because it is associated with significant morbidity and mortality. There is a debate over the effect of allograft nephrectomy on the development of allosensitization and the impact on potential retransplantation. Moreover, the use of immunosuppression may contribute to antibody allosensitization as allograft nephrectomy and immunosuppression act jointly and interdependently toward antibody formation. Because more and more patients with kidney allograft failure are entering wait lists for repeat transplant procedures, a review of available evidence on the field is required. Here, we performed a literature search using multiple medical databases to identify relevant studies that assessed the effects of allograft nephrectomy on important retransplant endpoints such as allograft and patient survival; furthermore, secondary outcomes such as alloantibody sensitization were also evaluated. A total of 15 studies were identified; all were retrospective, single-center studies. The rate of allograft nephrectomy in patients with retransplant varied widely (from 20% to 80%). The average allograft nephrectomy rate in included studies was 43% (allograft nephrectomy number/number of repeat transplantations: 2351/5431). Most studies did not observe an allograft survival benefit after retransplant for patients with allograft nephrectomy with the exception of 4 studies that found worse allograft survival after allograft nephrectomy. Interestingly, 1 study found that, in the patient subgroup with early kidney allograft failure (<12 months posttransplant), allograft nephrectomy may be associated with better allograft survival. Available data suggested that allograft nephrectomy may be associated with a higher risk of increasing anti-HLA antibody levels. The quality of the included studies suffered from nonrandomized design, potential confounding, and small sample size. To conclude, further randomized controlled trials are required to delineate the role of allograft nephrectomy on retransplant outcomes.
Topics: Allografts; Graft Rejection; Humans; Isoantibodies; Kidney; Kidney Transplantation; Nephrectomy; Reoperation; Retrospective Studies; Treatment Outcome
PubMed: 34775942
DOI: 10.6002/ect.2021.0133 -
Haematologica Aug 2022Vaccines against SARS-CoV-2 have shown remarkable efficacy and thus constitute an important preventive option against coronavirus disease 2019 (COVID-19), especially in... (Meta-Analysis)
Meta-Analysis
Vaccines against SARS-CoV-2 have shown remarkable efficacy and thus constitute an important preventive option against coronavirus disease 2019 (COVID-19), especially in fragile patients. We aimed to systematically analyze the outcomes of patients with hematological malignancies who received vaccination and to identify specific groups with differences in outcomes. The primary end point was antibody response after full vaccination (2 doses of mRNA or one dose of vectorbased vaccines). We identified 49 studies comprising 11,086 individuals. Overall risk of bias was low. The pooled response for hematological malignancies was 64% (95% confidence interval [CI]: 59-69; I²=93%) versus 96% (95% CI: 92-97; I²=44%) for solid cancer and 98% (95% CI: 96-99; I²=55%) for healthy controls (P<0.001). Outcome was different across hematological malignancies (P<0.001). The pooled response was 50% (95% CI: 43-57; I²=84%) for chronic lymphocytic leukemia, 76% (95% CI: 67-83; I²=92%) for multiple myeloma, 83% (95% CI: 69-91; I²=85%) for myeloproliferative neoplasms, 91% (95% CI: 82-96; I²=12%) for Hodgkin lymphoma, and 58% (95% CI: 44-70; I²=84%) for aggressive and 61% (95% CI: 48-72; I²=85%) for indolent non-Hodgkin lymphoma. The pooled response for allogeneic and autologous hematopoietic cell transplantation was 82% and 83%, respectively. Being in remission and prior COVID-19 showed significantly higher responses. Low pooled response was identified for active treatment (35%), anti-CD20 therapy ≤1 year (15%), Bruton kinase inhibition (23%), venetoclax (26%), ruxolitinib (42%), and chimeric antigen receptor T-cell therapy (42%). Studies on timing, value of boosters, and long-term efficacy are needed. This study is registered with PROSPERO (clinicaltrials gov. Identifier: CRD42021279051).
Topics: Adult; Antibody Formation; COVID-19; COVID-19 Vaccines; Hematologic Neoplasms; Humans; SARS-CoV-2; Vaccination
PubMed: 34911284
DOI: 10.3324/haematol.2021.280163 -
Rheumatology (Oxford, England) Oct 2019The clinical impact of anti-drug antibodies (ADAbs) in paediatric patients with JIA remains unknown. This systematic review and meta-analysis aimed to summarize the... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The clinical impact of anti-drug antibodies (ADAbs) in paediatric patients with JIA remains unknown. This systematic review and meta-analysis aimed to summarize the prevalence of ADAbs in JIA studies; investigate the effect of ADAbs on treatment efficacy and adverse events; and explore the effect of immunosuppressive therapy on antibody formation.
METHODS
PubMed, Embase and the Cochrane Library were systematically searched to identify relevant clinical trials and observational studies that reported prevalence of ADAbs. Studies were systematically reviewed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses and appropriate proportional and pairwise meta-analyses were performed.
RESULTS
A total of 5183 references were screened; 28 articles, involving 26 studies and 2354 JIA patients, met eligibility criteria. Prevalence of ADAbs ranged from 0% to 82% across nine biologic agents. Overall pooled prevalence of ADAbs was 16.9% (95% CI, 9.5, 25.9). Qualitative analysis of included studies indicated that antibodies to infliximab, adalimumab, anakinra and tocilizumab were associated with treatment failure and/or hypersensitivity reactions. Concomitant MTX uniformly reduced the risk of antibody formation during adalimumab treatment (risk ratio 0.33; 95% CI 0.21, 0.52).
CONCLUSION
The association of ADAbs with treatment failure and hypersensitivity reactions indicates their clinical relevance in paediatric patients with JIA. Based on our findings, we recommend a preliminary course of action regarding immunogenicity of biologic agents in patients with JIA. Further strategies to predict, prevent, detect and manage immunogenicity could optimize treatment outcomes and personalize treatment with biologic therapies.
Topics: Adalimumab; Antibodies, Monoclonal, Humanized; Antibody Formation; Antirheumatic Agents; Arthritis, Juvenile; Biological Factors; Child; Clinical Trials as Topic; Humans; Infliximab; Interleukin 1 Receptor Antagonist Protein; Methotrexate; Observational Studies as Topic
PubMed: 30809664
DOI: 10.1093/rheumatology/kez030