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Frontiers in Immunology 2020Aging is accompanied by alterations in immune response which leads to increased susceptibility to infectious diseases, cancer, autoimmunity, and inflammatory disorders....
BACKGROUND
Aging is accompanied by alterations in immune response which leads to increased susceptibility to infectious diseases, cancer, autoimmunity, and inflammatory disorders. This decline in immune function is termed as immunosenescence; however, the mechanisms are not fully elucidated. Experimental approaches of adaptive immunity, particularly for T cells, have been the main focus of immunosenescence research. This systematic review evaluates and discusses T cell markers implicated in immunosenescence.
OBJECTIVE
To determine the best flow cytometry markers of circulating T cells associated with immunosenescence.
METHODS
We systematically queried PubMed, MEDLINE, EBSCO, and BVS databases for original articles focused on two age groups of healthy humans: 18-44 (young adults) and >60 (older adults) years. In accordance with the Cochrane methodology, we synthesized data through qualitative descriptions and quantitative random effects meta-analysis due to extensive heterogeneity.
RESULTS
A total of 36 studies conducted in the last 20 years were included for the qualitative analysis and four out of these studies were used to perform the meta-analysis. A significant decrease in naïve T cell subset was observed in older adults compared to young adults. Primary markers used to identify senescent cells were loss of CD28 and increased expression of CD57 and KLRG1 in terminally-differentiated memory T cell subset in older adults. Moreover, we observed an increase in proinflammatory cytokines and decrease in telomere length in old adult T cells. It was not possible to perform quantitative synthesis on cell markers, cytokines, and telomere length because of the significant variations between the groups, which is attributed to differences in protocols and unreported measurements, thus generating a high risk of bias.
CONCLUSIONS
Heterogeneity among studies in terms of data report, measurement techniques and high risk of bias were major impediments for performing a robust statistical analysis that could aid the identification of eligible flow cytometry markers of immunosenescence phenotype in T cells.
Topics: Adolescent; Adult; Age Factors; Antigens, CD; Biomarkers; Cytokines; Flow Cytometry; Humans; Immunologic Memory; Immunophenotyping; Immunosenescence; Phenotype; T-Lymphocyte Subsets; Telomere Shortening; Young Adult
PubMed: 33519813
DOI: 10.3389/fimmu.2020.604591 -
Viruses Mar 2022During HIV/SIV infection, the upregulation of immune checkpoint (IC) markers, programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4... (Review)
Review
During HIV/SIV infection, the upregulation of immune checkpoint (IC) markers, programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), T cell immunoglobulin and ITIM domain (TIGIT), lymphocyte-activation gene-3 (LAG-3), T cell immunoglobulin and mucin domain-3 (Tim-3), CD160, 2B4 (CD244), and V-domain Ig suppressor of T cell activation (VISTA), can lead to chronic T cell exhaustion. These ICs play predominant roles in regulating the progression of HIV/SIV infection by mediating T cell responses as well as enriching latent viral reservoirs. It has been demonstrated that enhanced expression of ICs on CD4 and CD8 T cells could inhibit cell proliferation and cytokine production. Overexpression of ICs on CD4 T cells could also format and prolong HIV/SIV persistence. IC blockers have shown promising clinical results in HIV therapy, implying that targeting ICs may optimize antiretroviral therapy in the context of HIV suppression. Here, we systematically review the expression profile, biological regulation, and therapeutic efficacy of targeted immune checkpoints in HIV/SIV infection.
Topics: Animals; CD8-Positive T-Lymphocytes; Disease Progression; HIV Infections; Humans; Immunoglobulins; Lymphocyte Activation; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus
PubMed: 35336991
DOI: 10.3390/v14030581 -
Epigenetics Aug 2021N6-methyladenosine (m6A), the most prevalent RNA internal modification, is present in most eukaryotic species and prokaryotes. Studies have highlighted an intricate...
N6-methyladenosine (m6A), the most prevalent RNA internal modification, is present in most eukaryotic species and prokaryotes. Studies have highlighted an intricate network architecture by which m6A epitranscriptome impacts on immune response and function. However, it was only until recently that the mechanisms underlying the involvement of m6A modification in immune system were uncovered. Here, we systematically review the m6A involvement in the regulation of innate and adaptive immune cells. Further, the interplay between m6A modification and anti-inflammatory, anti-viral and anti-tumour immunity is also comprehensively summarized. Finally, we focus on the future prospects of m6A modification in immune modulation. A better understanding of the crosstalk between m6A modification and immune system is of great significance to reveal new pathogenic pathways and to develop promising therapeutic targets of diseases.
Topics: Adenosine; DNA Methylation; Immune System; Logic
PubMed: 33070685
DOI: 10.1080/15592294.2020.1827722 -
JAMA Network Open Apr 2022Recipients of solid organ transplant (SOT) experience decreased immunogenicity after COVID-19 vaccination. (Meta-Analysis)
Meta-Analysis
Immunogenicity and Risk Factors Associated With Poor Humoral Immune Response of SARS-CoV-2 Vaccines in Recipients of Solid Organ Transplant: A Systematic Review and Meta-Analysis.
IMPORTANCE
Recipients of solid organ transplant (SOT) experience decreased immunogenicity after COVID-19 vaccination.
OBJECTIVE
To summarize current evidence on vaccine responses and identify risk factors for diminished humoral immune response in recipients of SOT.
DATA SOURCES
A literature search was conducted from existence of database through December 15, 2021, using MEDLINE, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov.
STUDY SELECTION
Studies reporting humoral immune response of the COVID-19 vaccines in recipients of SOT were reviewed.
DATA EXTRACTION AND SYNTHESIS
Two reviewers independently extracted data from each eligible study. Descriptive statistics and a random-effects model were used. This report was prepared following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data were analyzed from December 2021 to February 2022.
MAIN OUTCOMES AND MEASURES
The total numbers of positive immune responses and percentage across each vaccine platform were recorded. Pooled odds ratios (pORs) with 95% CIs were used to calculate the pooled effect estimates of risk factors for poor antibody response.
RESULTS
A total of 83 studies were included for the systematic review, and 29 studies were included in the meta-analysis, representing 11 713 recipients of SOT. The weighted mean (range) of total positive humoral response for antispike antibodies after receipt of mRNA COVID-19 vaccine was 10.4% (0%-37.9%) for 1 dose, 44.9% (0%-79.1%) for 2 doses, and 63.1% (49.1%-69.1%) for 3 doses. In 2 studies, 50% of recipients of SOT with no or minimal antibody response after 3 doses of mRNA COVID-19 vaccine mounted an antibody response after a fourth dose. Among the factors associated with poor antibody response were older age (mean [SE] age difference between responders and nonresponders, 3.94 [1.1] years), deceased donor status (pOR, 0.66 [95% CI, 0.53-0.83]; I2 = 0%), antimetabolite use (pOR, 0.21 [95% CI, 0.14-0.29]; I2 = 70%), recent rituximab exposure (pOR, 0.21 [95% CI, 0.07-0.61]; I2 = 0%), and recent antithymocyte globulin exposure (pOR, 0.32 [95% CI, 0.15-0.71]; I2 = 0%).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis, the rates of positive antibody response in solid organ transplant recipients remained low despite multiple doses of mRNA vaccines. These findings suggest that more efforts are needed to modulate the risk factors associated with reduced humoral responses and to study monoclonal antibody prophylaxis among recipients of SOT who are at high risk of diminished humoral response.
Topics: COVID-19; COVID-19 Vaccines; Child, Preschool; Humans; Immunity, Humoral; Organ Transplantation; RNA, Messenger; Risk Factors; SARS-CoV-2
PubMed: 35412626
DOI: 10.1001/jamanetworkopen.2022.6822 -
Current Rheumatology Reports Jul 2015In 2011, the European League Against Rheumatism (EULAR) published recommendations regarding the vaccination of children with rheumatic diseases. These recommendations... (Review)
Review
In 2011, the European League Against Rheumatism (EULAR) published recommendations regarding the vaccination of children with rheumatic diseases. These recommendations were based on a systematic literature review published in that same year. Since then, the evidence body on this topic has grown substantially. This review provides an update of the systematic literature study of 2011, summarizing all the available evidence on the safety and immunogenicity of vaccination in paediatric patients with rheumatic diseases. The current search yielded 21 articles, in addition to the 27 articles described in the 2011 review. In general, vaccines are immunogenic and safe in this patient population. The effect of immunosuppressive drugs on the immunogenicity of vaccines was not detrimental for glucocorticosteroids and methotrexate. Biologicals could accelerate a waning of antibody levels over time, although most patients were initially protected adequately. Overall, persistence of immunological memory may be reduced in children with rheumatic diseases, which shows the need for (booster) vaccination. This update of the 2011 systematic literature review strengthens the evidence base for the EULAR recommendations, and it must be concluded that vaccinations in patients with rheumatic diseases should be advocated.
Topics: Child; Humans; Immunity, Active; Patient Safety; Rheumatic Diseases; Treatment Outcome; Vaccination; Vaccines
PubMed: 26025339
DOI: 10.1007/s11926-015-0519-y -
Journal of Alternative and... May 2013The aim of this review is to summarize and assess critically clinical trial evidence of the effect of t'ai chi (TC) exercise on immunity and TC efficacy for treating... (Review)
Review
PURPOSE
The aim of this review is to summarize and assess critically clinical trial evidence of the effect of t'ai chi (TC) exercise on immunity and TC efficacy for treating infectious diseases.
METHODS
Fourteen databases were searched from their respective inceptions through January 2011. No language restrictions were imposed. Quality and validity of the included clinical trials were evaluated using standard scales.
RESULTS
Sixteen (16) studies, including 7 randomized controlled trials, 4 controlled clinical trials, and 5 retrospective case-control studies, met the inclusion criteria for this review. One (1) study examined clinical symptoms, 3 studies tested functional measures of immunity (antigen-induced immunity), and the other studies tested enumerative parameters of immunity. such as lymphocytes, immunoglobulins, complements, natural-killer cells, and myeloid dendritic cells. Overall, these studies suggested favorable effects of TC exercise.
CONCLUSIONS
TC exercise appears to improve both cell-mediated immunity and antibody response in immune system, but it remains debatable whether or not the changes in immune parameters are sufficient to provide protection from infections.
Topics: Adult; Aged; Aged, 80 and over; Antibody Formation; Complement System Proteins; Controlled Clinical Trials as Topic; Female; Humans; Immunity, Cellular; Immunocompetence; Immunoglobulins; Infections; Lymphocyte Count; Male; Middle Aged; Randomized Controlled Trials as Topic; Tai Ji
PubMed: 23317394
DOI: 10.1089/acm.2011.0593 -
Transplantation Sep 2016Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation. Chronic lung allograft dysfunction manifests as... (Review)
Review
Chronic lung allograft dysfunction (CLAD) is the major limitation of long-term survival after lung transplantation. Chronic lung allograft dysfunction manifests as bronchiolitis obliterans syndrome or the recently described restrictive allograft syndrome. Although numerous risk factors have been identified so far, the physiopathological mechanisms of CLAD remain poorly understood. We investigate here the immune mechanisms involved in the development of CLAD after lung transplantation. We explore the innate or adaptive immune reactions induced by the allograft itself or by the environment and how they lead to allograft dysfunction. Because current literature suggests bronchiolitis obliterans syndrome and restrictive allograft syndrome as 2 distinct entities, we focus on the specific factors behind one or the other syndromes. Chronic lung allograft dysfunction is a multifactorial disease that remains irreversible and unpredictable so far. We thus finally discuss the potential of systems-biology approach to predict its occurrence and to better understand its underlying mechanisms.
Topics: Adaptive Immunity; Allografts; Animals; Bronchiolitis Obliterans; Chronic Disease; Graft Survival; Humans; Immunity, Innate; Lung; Lung Transplantation; Risk Factors; Syndrome; Systems Biology; Time Factors; Treatment Outcome
PubMed: 27257997
DOI: 10.1097/TP.0000000000001215 -
PloS One 2022Pregnancy is a known risk factor for severe Coronavirus disease 2019. It is important to develop safe vaccines that elicit strong maternal and fetal antibody responses.
OBJECTIVE
Pregnancy is a known risk factor for severe Coronavirus disease 2019. It is important to develop safe vaccines that elicit strong maternal and fetal antibody responses.
METHODS
Registries (ClinicalTrials.gov, the WHO Clinical Trial Registry, and the European Union Clinical Trial Registry) and databases (MEDLINE, ScienceDirect, Cochrane Library, Proquest, Springer, medRxiv, and bioRxiv) were systematically searched in June 20-22, 2021, for research articles pertaining to Covid-19 and pregnancy. Manual searches of bioRxiv and medRxiv were also conducted. Inclusion criteria were studies that focused on Covid-19 vaccination among pregnant women, while review articles and non-human studies were excluded. Infection rate, maternal antibody response, transplacental antibody transfer, and adverse events were described.
RESULTS
There were 13 observational studies with a total of 48,039 pregnant women who received mRNA vaccines. Of those, three studies investigated infection rate, six studies investigated maternal antibody response, seven studies investigated antibody transfer, three studies reported local adverse events, and five studies reported systemic adverse events. The available data suggested that the mRNA-based vaccines (Pfizer-BioNTech and Moderna) can prevent future SARS-CoV-2 infection. These vaccines did not show clear harm in pregnancy. The most commonly encountered adverse reactions were pain at the injection site, fatigue, and headache, but these were transient. Antibody responses were rapid after the first vaccine dose. After the booster, antibody responses were stronger and associated with better transplacental antibody transfer. Longer intervals between first vaccination dose and delivery were also associated with higher antibody fetal IgG and a better antibody transfer ratio.
CONCLUSIONS
The SARS-CoV-2 mRNA vaccines are encouraged for pregnancy. These vaccines can be a safe option for pregnant women and their fetuses. Two vaccine doses are recommended for more robust maternal and fetal antibody responses. Longer latency is associated with higher fetal antibody responses. Further research about its long-term effect on pregnancy is needed.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO (CRD42021261684).
Topics: 2019-nCoV Vaccine mRNA-1273; Adult; Animals; Antibodies, Viral; Antibody Formation; BNT162 Vaccine; COVID-19; COVID-19 Vaccines; Databases, Factual; Female; Humans; Immunogenicity, Vaccine; Immunoglobulin G; Pregnancy; Registries; SARS-CoV-2; Vaccination; mRNA Vaccines
PubMed: 35108277
DOI: 10.1371/journal.pone.0261350 -
International Journal of Environmental... Jun 2022Approximately 2.9 million people worldwide suffer from cholera each year, many of whom are destitute. However, understanding of immunity against cholera is still... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Approximately 2.9 million people worldwide suffer from cholera each year, many of whom are destitute. However, understanding of immunity against cholera is still limited. Several studies have reported the duration of antibodies following cholera; however, systematic reviews including a quantitative synthesis are lacking.
OBJECTIVE
To meta-analyze cohort studies that have evaluated vibriocidal, cholera toxin B subunit (CTB), and lipopolysaccharide (LPS) antibody levels following a clinical cholera case.
METHODS
Design: Systematic review and meta-analysis. We searched PubMed and Web of science for studies assessing antibodies against in cohorts of patients with clinical cholera. Two authors independently extracted data and assessed the quality of included studies. Random effects models were used to pool antibody titers in adults and older children (aged ≥ 6 years). In sensitivity analysis, studies reporting data on young children (2-5 years) were included.
RESULTS
Nine studies met our inclusion criteria for systematic review and seven for meta-analysis. The pooled mean of vibriocidal antibody titers in adults and older children (aged ≥ 6 years) was 123 on day 2 post-symptom onset, which sharply increased on day 7 (pooled mean = 6956) and gradually waned to 2247 on day 30, 578 on day 90, and 177 on day 360. Anti-CTB IgA antibodies also peaked on day 7 (pooled mean = 49), followed by a rapid decrease on day 30 (pooled mean = 21), and further declined on day 90 (pooled mean = 10), after which it plateaued from day 180 (pooled mean = 8) to 360 (pooled mean = 6). Similarly, anti-CTB IgG antibodies peaked in early convalescence between days 7 (pooled mean = 65) and 30 (pooled mean = 69), then gradually waned on days 90 (pooled mean = 42) and 180 (pooled mean = 30) and returned to baseline on day 360 (pooled mean = 24). Anti-LPS IgA antibodies peaked on day 7 (pooled mean = 124), gradually declined on day 30 (pooled mean = 44), which persisted until day 360 (pooled mean = 10). Anti LPS IgG antibodies peaked on day 7 (pooled mean = 94). Thereafter, they decreased on day 30 (pooled mean = 85), and dropped further on days 90 (pooled mean = 51) and 180 (pooled mean = 47), and returned to baseline on day 360 (pooled mean = 32). Sensitivity analysis including data from young children (aged 2-5 years) showed very similar findings as in the primary analysis.
CONCLUSIONS
This study confirms that serological antibody (vibriocidal, CTB, and LPS) titers return to baseline levels within 1 year following clinical cholera, i.e., before the protective immunity against subsequent cholera wanes. However, this decay should not be interpreted as waning immunity because immunity conferred by cholera against subsequent disease lasts 3-10 years. Our study provides evidence for surveillance strategies and future research on vaccines and also demonstrates the need for further studies to improve our understanding of immunity against cholera.
Topics: Adolescent; Adult; Antibodies, Bacterial; B-Lymphocytes; Child; Child, Preschool; Cholera; Humans; Immunoglobulin A; Immunoglobulin G; Immunologic Memory; Kinetics; Lipopolysaccharides; Vibrio cholerae O1
PubMed: 35742404
DOI: 10.3390/ijerph19127141 -
Frontiers in Immunology 2022Recovery from coronavirus disease 2019 (COVID-19) can be impaired by the persistence of symptoms or new-onset health complications, commonly referred to as Long COVID.... (Review)
Review
BACKGROUND
Recovery from coronavirus disease 2019 (COVID-19) can be impaired by the persistence of symptoms or new-onset health complications, commonly referred to as Long COVID. In a subset of patients, Long COVID is associated with immune system perturbations of unknown etiology, which could be related to compromised immunoregulatory mechanisms.
OBJECTIVE
The objective of this scoping review was to summarize the existing literature regarding the frequency and functionality of Tregs in convalescent COVID-19 patients and to explore indications for their potential involvement in the development of Long COVID.
DESIGN
A systematic search of studies investigating Tregs during COVID-19 convalescence was conducted on MEDLINE ( Pubmed) and Web of Science.
RESULTS
The literature search yielded 17 relevant studies, of which three included a distinct cohort of patients with Long COVID. The reviewed studies suggest that the Treg population of COVID-19 patients can reconstitute quantitatively and functionally during recovery. However, the comparison between recovered and seronegative controls revealed that an infection-induced dysregulation of the Treg compartment can be sustained for at least several months. The small number of studies investigating Tregs in Long COVID allowed no firm conclusions to be drawn about their involvement in the syndrome's etiology. Yet, even almost one year post-infection Long COVID patients exhibit significantly altered proportions of Tregs within the CD4+ T cell population.
CONCLUSIONS
Persistent alterations in cell frequency in Long COVID patients indicate that Treg dysregulation might be linked to immune system-associated sequelae. Future studies should aim to address the association of Treg adaptations with different symptom clusters and blood parameters beyond the sole quantification of cell frequencies while adhering to consensualized phenotyping strategies.
Topics: Humans; CD4-Positive T-Lymphocytes; COVID-19; Post-Acute COVID-19 Syndrome; T-Lymphocytes, Regulatory
PubMed: 36582234
DOI: 10.3389/fimmu.2022.1070994