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Immunology May 2022Chronic lung allograft dysfunction (CLAD) remains the major barrier to long-term survival after lung transplantation and improved insight into its underlying... (Review)
Review
Chronic lung allograft dysfunction (CLAD) remains the major barrier to long-term survival after lung transplantation and improved insight into its underlying immunological mechanisms is critical to better understand the disease and to identify treatment targets. We systematically searched the electronic databases of PubMed and EMBASE for original research publications, published between January 2000 and April 2021, to comprehensively assess current evidence on effector immune cells in lung tissue and bronchoalveolar lavage fluid from lung transplant recipients with CLAD. Literature search revealed 1351 articles, 76 of which met the criteria for inclusion in our analysis. Our results illustrate significant complexity in both innate and adaptive immune cell responses in CLAD, along with presence of numerous immune cell products, including cytokines, chemokines and proteases associated with tissue remodelling. A clear link between neutrophils and eosinophils and CLAD incidence has been seen, in which eosinophils more specifically predisposed to restrictive allograft syndrome. The presence of cytotoxic and T-helper cells in CLAD pathogenesis is well-documented, although it is challenging to draw conclusions about their role in tissue processes from predominantly bronchoalveolar lavage data. In restrictive allograft syndrome, a more prominent humoral immune involvement with increased B cells, immunoglobulins and complement deposition is seen. Our evaluation of published studies over the last 20 years summarizes the complex multifactorial immunopathology of CLAD onset and progression. It highlights the phenotype of several key effector immune cells involved in CLAD pathogenesis, as well as the paucity of single cell resolution spatial studies in lung tissue from patients with CLAD.
Topics: Allografts; Bronchoalveolar Lavage Fluid; Chronic Disease; Graft vs Host Disease; Humans; Lung; Lung Transplantation; Retrospective Studies; Transplantation, Homologous
PubMed: 35137398
DOI: 10.1111/imm.13458 -
Clinical Science (London, England :... Mar 2012Diabetes is a mutifactorial metabolic disorder that leads to a number of complications. Diabetes is estimated to affect 36 million people in the U.S.A., and the... (Review)
Review
Diabetes is a mutifactorial metabolic disorder that leads to a number of complications. Diabetes is estimated to affect 36 million people in the U.S.A., and the prevalence of diagnosed and undiagnosed diabetes is at 9.3% and continues to rise. Evidence from experimental animal models as well as humans has indicated that systemic inflammation plays a role in the pathophysiological processes of diabetes and is facilitated by innate immune responses. TLRs (Toll-like receptors) are key innate immune receptors that recognize conserved PAMPs (pathogen-associated molecular patterns), induce inflammatory responses essential for host defences and initiate an adaptive immune response. Although TLR expression is increased in a plethora of inflammatory disorders, the effects of metabolic aberrations on TLRs and their role in diabetes and its complications is still emerging. In the present paper, we provide a systematic review on how TLRs play a detrimental role in the pathogenic processes [increased blood sugar, NEFAs (non-esterified 'free' fatty acids), cytokines and ROS (reactive oxygen species)] that manifest diabetes. Furthermore, we will highlight some of the therapeutic strategies targeted at decreasing TLRs to abrogate inflammation in diabetes that may eventually result in decreased complications.
Topics: Blood Glucose; Cytokines; Diabetes Complications; Diabetes Mellitus; Fatty Acids, Nonesterified; Humans; Hyperglycemia; Immunity, Innate; Inflammation; Reactive Oxygen Species; Signal Transduction; Toll-Like Receptors
PubMed: 22070434
DOI: 10.1042/CS20110357 -
Journal of Gastrointestinal Cancer Mar 2024T cell exhaustion and activation markers are helpful in determining the therapies and predicting the overall survival in pancreatic cancer (PC) patients. (Review)
Review
BACKGROUND
T cell exhaustion and activation markers are helpful in determining the therapies and predicting the overall survival in pancreatic cancer (PC) patients.
PURPOSE
In this systematic review, we have addressed two questions, how do these markers differ in their expression levels in PC patients and healthy individual and correlating the expression level of these markers with the cancer stage.
METHODS
The systematic review was registered with Prospective Register of Systematic Reviews (PROSPERO) with registration number "CRD42022246780." All the included articles were obtained from three databases, PubMed, MEDLINE, and Cochrane, published from January 2010 to 26th May 2022. Two independent reviewers followed the PRISM protocol and reviewed and extracted data from the included articles.
RESULTS
PD-1 and CTLA-4 were the most studied markers in this field. A clear elevation in the expression of PD-1, CTLA-4, TIM-3, LAG-3, and TIGIT was found in most of the studies. CD69, CD25, and HLA-DR expression was found to be upregulated after chemotherapy and immunotherapy. CD25 was the only marker analyzed against cancer progression, in a single study. No study compared the expression of exhaustion and activation markers (except CD69) with the cancer progression of the tumor stage.
CONCLUSION
Since the exhaustion markers are upregulated in patients, single or multiple markers can be targeted in immunotherapies. Knowledge of the dynamics of these markers at various cancer stages will help in determining the right immunotherapy for pancreatic cancer patients. Stage-wise comparison could also be made possible by developing in vitro models.
Topics: Humans; Pancreatic Neoplasms; Biomarkers, Tumor; T-Lymphocytes; CTLA-4 Antigen; Lymphocyte Activation; T-Cell Exhaustion
PubMed: 37672169
DOI: 10.1007/s12029-023-00965-w -
Surgical Endoscopy Feb 2024Laparoscopic surgery (LS) is hypothesized to result in milder proinflammatory reactions due to less severe operative trauma, which may contribute to the observed... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Laparoscopic surgery (LS) is hypothesized to result in milder proinflammatory reactions due to less severe operative trauma, which may contribute to the observed clinical benefits after LS. However, previous systematic reviews and meta-analyses on the impact of LS on immunocompetence are outdated, limited and heterogeneous. Therefore, the humoral response after laparoscopic and open colorectal cancer (CRC) resections was evaluated in a comprehensive systematic review and meta-analysis.
METHODS
Included were randomized controlled trials (RCTs) measuring parameters of humoral immunity after LS compared to open surgery (OS) in adult patients with CRC of any stage. MEDLINE, Embase, Web of Science (SCI-EXPANDED), Cochrane Library, Google Scholar, ClinicalTrials.gov and ICTRP (World Health Organization) were systematically searched. Risk of bias (RoB) was assessed using the Cochrane RoB2 tool. Weighted inverse variance meta-analysis of mean differences was performed for C-reactive protein (CRP), interleukin (IL)-6, IL-8, tumour necrosis factor (TNF)α and vascular endothelial growth factor (VEGF) using the random-effects method. Methods were prospectively registered in PROSPERO (CRD42021264324).
RESULTS
Twenty RCTs with 1131 participants were included. Narrative synthesis and meta-analysis up to 8 days after surgery was performed. Quantitative synthesis found concentrations to be significantly lower after LS at 0-2 h after surgery (IL-8), at 3-9 h (CRP, IL-6, IL-8, TNFα) and at postoperative day 1 (CRP, IL-6, IL-8, VEGF). At 3-9 h, IL-6 was notably lower in the LS group by 86.71 pg/ml (mean difference [MD] - 86.71 pg/ml [- 125.05, - 48.37], p < 0.00001). Combined narratively, 13 studies reported significantly lower concentrations of considered parameters in LS patients, whereas only one study reported lower inflammatory markers (for CRP and IL-6) after OS.
CONCLUSION
The increase in postoperative concentrations of several proinflammatory parameters was significantly less pronounced after LS than after OS in this meta-analysis. Overall, the summarized evidence reinforces the view of a lower induction of inflammation due to LS.
Topics: Adult; Humans; Immunity, Humoral; Interleukin-6; Interleukin-8; Vascular Endothelial Growth Factor A; Laparoscopy; C-Reactive Protein; Colorectal Neoplasms; Randomized Controlled Trials as Topic
PubMed: 38102395
DOI: 10.1007/s00464-023-10582-0 -
International Journal of Molecular... Nov 2023Behçet's disease (BD) is a complex, recurring inflammatory disorder with autoinflammatory and autoimmune components. This comprehensive review aims to explore BD's... (Review)
Review
Behçet's disease (BD) is a complex, recurring inflammatory disorder with autoinflammatory and autoimmune components. This comprehensive review aims to explore BD's pathogenesis, focusing on established genetic factors. Studies reveal that is the primary genetic risk factor, but non-HLA genes (, , ), as well as innate immunity genes (, , ), also contribute. Genome-wide studies emphasize the significance of and HLA-I epistasis. These variants influence antigen presentation, enzymatic activity, and HLA-I peptidomes, potentially leading to distinct autoimmune responses. We conducted a systematic review of the literature to identify studies exploring the association between and BD and further highlighted the roles of innate and adaptive immunity in BD. Dysregulations in Th1/Th2 and Th17/Th1 ratios, heightened clonal cytotoxic (CD8+) T cells, and reduced T regulatory cells characterize BD's complex immune responses. Various immune cell types (neutrophils, γδ T cells, natural killer cells) further contribute by releasing cytokines (IL-17, IL-8, GM-CSF) that enhance neutrophil activation and mediate interactions between innate and adaptive immunity. In summary, this review advances our understanding of BD pathogenesis while acknowledging the research limitations. Further exploration of genetic interactions, immune dysregulation, and immune cell roles is crucial. Future studies may unveil novel diagnostic and therapeutic strategies, offering improved management for this complex disease.
Topics: Humans; Behcet Syndrome; Antigen Presentation; Genetic Predisposition to Disease; HLA-B Antigens; Risk Factors; Aminopeptidases; Minor Histocompatibility Antigens
PubMed: 38003572
DOI: 10.3390/ijms242216382 -
The British Journal of Dermatology Jan 2020Atopic dermatitis (AD) is a multifactorial and complex disease, characterized by an impaired skin barrier function and abnormal immune response. Many elderly patients... (Review)
Review
BACKGROUND
Atopic dermatitis (AD) is a multifactorial and complex disease, characterized by an impaired skin barrier function and abnormal immune response. Many elderly patients present with pruritus and xerosis to dermatology, allergy and primary care clinics, and there is a lack of information available to clinicians regarding the proper diagnosis and management of these patients. Although the elderly are described as having a distinct presentation of AD and important comorbidities, most investigations and clinical care guidelines pertaining to AD do not include patients aged 60 years and older as a separate group from younger adults.
OBJECTIVES
To summarize current information on pathophysiology, diagnosis and management of AD in the elderly population and identify areas of insufficient information to be explored in future investigations.
METHODS
We carried out a systematic review of published literature, which assessed changes in the skin barrier and immune function with ageing and current information available for physicians to use in the diagnosis and treatment of AD in elderly patients.
RESULTS
Many age-related changes overlap with key hallmarks observed in AD, most notably a decline in skin barrier function, dysregulation of the innate immune system, and skewing of adaptive immunity to a type-2 T helper cell response, in addition to increased Staphylococcus aureus infection.
CONCLUSIONS
While general physiological alterations with ageing overlap with key features of AD, a research gap exists regarding specific ageing-related changes in AD disease development. More knowledge about AD in the elderly is needed to establish firm diagnostic and treatment methodologies. What's already known about this topic? Atopic dermatitis (AD) is a common inflammatory skin disease that causes significant burden worldwide. Recently, elderly patients have been considered a subgroup of patients with distinct AD manifestation. Limited studies have characterized the clinical presentation and role of IgE-mediated allergy in elderly patients with AD. What does this study add? This review offers a summary of age-related skin and immune alterations that correspond to pathogenic changes noted in patients with AD. The role of itch, environmental factors and skin microbiota in AD disease presentation in ageing patients is explored.
Topics: Adaptive Immunity; Adult; Aged; Dermatitis, Atopic; Eczema; Humans; Middle Aged; Pruritus; Skin
PubMed: 30895603
DOI: 10.1111/bjd.17896 -
Experimental Gerontology May 2016Immunosenescence is the age-related deterioration of immunocompetence which is reflected in a poorer response to new antigens. This process is characterized by decreases... (Review)
Review
INTRODUCTION
Immunosenescence is the age-related deterioration of immunocompetence which is reflected in a poorer response to new antigens. This process is characterized by decreases in naïve T cells and increases in memory T cells. The highly prevalent β-herpesvirus cytomegalovirus (CMV) is thought to enhance T-cell immunosenescence. The aim of this study was to perform a systematic review on the current evidence regarding the relation between CMV-infection and immunosenescence in Western people aged fifty years and older.
METHODS
Studies that investigated the relation between CMV infection and immune parameters in Western people aged 50 years and older were eligible for inclusion. No restrictions were placed on study type. This article focuses on the relation between CMV infections as measured by serology and T cell subsets. A narrative approach to data synthesis was applied.
RESULTS
In the majority of included studies higher levels of Effector Memory (EM) and TEMRA (Effector Memory T cells re-expressing CD45RA) cells were found in the CD4+ and the CD8+ T cell pools in CMV-seropositive elderly compared to CMV-seronegative elderly. No clear evidence was found for lower levels of naïve T cells in CMV-seropositive elderly compared to CMV-seronegative elderly. The total CD8+ T cell pool appeared to be larger in CMV-seropositive elderly in three out of four studies, while the total CD4+ T cell pool appeared to be smaller in CMV-seropositive elderly in two out of four studies.
DISCUSSION
CMV seems to enhance immunosenescence based on the high levels of the highly differentiated EM and TEMRA cells in the CD8+ and CD4+ T cell pools. The relation of the shifts within the T cell compartments in CMV-seropositive elderly in relation to susceptibility to infectious diseases remains to be investigated.
Topics: Aged; Cytomegalovirus; Cytomegalovirus Infections; Humans; Immunologic Memory; Immunosenescence; Middle Aged; T-Lymphocytes
PubMed: 26883338
DOI: 10.1016/j.exger.2016.02.005 -
Expert Reviews in Molecular Medicine Aug 2021Otitis media (OM) is a common reason for children to be prescribed antibiotics and undergo surgery but a thorough understanding of disease mechanisms is lacking. We...
OBJECTIVE
Otitis media (OM) is a common reason for children to be prescribed antibiotics and undergo surgery but a thorough understanding of disease mechanisms is lacking. We evaluate the evidence of a dysregulated immune response in the pathogenesis of OM.
METHODS
A comprehensive systematic review of the literature using search terms [otitis media OR glue ear OR AOM OR OME] OR [middle ear AND (infection OR inflammation)] which were run through Medline and Embase via Ovid, including both human and animal studies. In total, 82 955 studies underwent automated filtering followed by manual screening. One hundred studies were included in the review.
RESULTS
Most studies were based on in vitro or animal work. Abnormalities in pathogen detection pathways, such as Toll-like receptors, have confirmed roles in OM. The aetiology of OM, its chronic subgroups (chronic OM, persistent OM with effusion) and recurrent acute OM is complex; however, inflammatory signalling mechanisms are frequently implicated. Host epithelium likely plays a crucial role, but the characterisation of human middle ear tissue lags behind that of other anatomical subsites.
CONCLUSIONS
Translational research for OM presently falls far behind its clinical importance. This has likely hindered the development of new diagnostic and treatment modalities. Further work is urgently required; particularly to disentangle the respective immune pathologies in the clinically observed phenotypes and thereby work towards more personalised treatments.
Topics: Animals; Anti-Bacterial Agents; Ear, Middle; Humans; Immunity; Otitis Media; Signal Transduction
PubMed: 34404500
DOI: 10.1017/erm.2021.10 -
International Journal of Pediatric... Jan 2006Chronic suppurative otitis media (CSOM) remains one of the most common childhood chronic infectious diseases worldwide. Although microbial, immunological, and... (Review)
Review
OBJECTIVES
Chronic suppurative otitis media (CSOM) remains one of the most common childhood chronic infectious diseases worldwide. Although microbial, immunological, and genetically determined factors, as well as Eustachian tube characteristics, are supposed to be involved in the pathogenesis of CSOM, many aspects of the pathogenesis of CSOM still need to be clarified. Optimal treatment strategy has not been established yet. The objective of this review is to present and evaluate the current state of knowledge of CSOM.
DESIGN
Systematic narrative review.
METHODS
A PubMed search (1966-January 2005) was performed for studies on epidemiology, pathogenesis, clinical management, and complications of CSOM. All included articles were categorized according to level of evidence.
RESULTS
Five hundred and fifty papers were identified, of which 79 were found to be relevant for this review. The definition of CSOM was found to vary. CSOM is a multifactorial disease. Regarding management of CSOM, there is no consensus as to what the optimal management strategy should entail. No convincing evidence is available for most medical and surgical therapies. Topical quinolones have proven effective, but need further monitoring regarding adverse effects.
CONCLUSIONS AND RECOMMENDATIONS
Important goals in research of CSOM should be achieving consensus about the definition of CSOM and gaining more in-depth knowledge of the pathogenesis of CSOM, especially the role of innate and adaptive immunity. There is also a need for further well-designed studies on the effectiveness of various management strategies for CSOM.
Topics: Anti-Infective Agents; Chronic Disease; Eustachian Tube; Hearing Aids; Humans; Middle Ear Ventilation; Otitis Media, Suppurative; Recurrence; Risk Factors
PubMed: 16198004
DOI: 10.1016/j.ijporl.2005.08.021 -
Veterinary Immunology and... May 2013Inactivated Parapoxvirus ovis (iPPVO) and Propionibacterium acnes (P. acnes) are currently used in equine medicine as immune-modulators for prophylactic treatment or... (Review)
Review
Inactivated Parapoxvirus ovis (iPPVO) and Propionibacterium acnes (P. acnes) are currently used in equine medicine as immune-modulators for prophylactic treatment or adjunct to conventional therapy in order to improve immune defences, to prevent or treat infectious diseases. Their mode of action relies on a non-antigen specific interaction with the innate and/or adaptive immune responses. iPPVO stimulates and regulates cytokine secretion by leucocytes, while P. acnes acts primarily through the activation of macrophages. This report aims to describe their activity as immune-modulators and to summarise the scientific literature and reports available about their use in horses, particularly in the prevention or treatment of equine respiratory diseases. This systematic review regroups articles published in peer-review journals, clinical trials reports, conference proceedings and other information made available in the last 2 decades.
Topics: Animals; Horse Diseases; Horses; Immunity, Innate; Immunologic Factors; Parapoxvirus; Propionibacterium acnes; Respiratory Tract Infections
PubMed: 23481655
DOI: 10.1016/j.vetimm.2013.01.010