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Pediatric Allergy and Immunology :... Jun 2024Basophil activation test (BAT) or the mast cell activation test (MAT) are two in vitro tests that are currently being studied in food allergy as diagnostic tools as an... (Meta-Analysis)
Meta-Analysis Review
Basophil activation test (BAT) or the mast cell activation test (MAT) are two in vitro tests that are currently being studied in food allergy as diagnostic tools as an alternative to oral food challenges (OFCs). We conducted a meta-analysis on BAT and MAT, assessing their specificity and sensitivity in diagnosing peanut allergy. Six databases were searched for studies on patients suspected of having peanut allergy. Studies using BAT or MAT to peanut extract and/or component as diagnostic tools with results given in percentage of CD63 activation were included in this meta-analysis. Study quality was evaluated with the QUADAS-2 tool. On the 11 studies identified, eight focused exclusively on children, while three included a mixed population of adults and children. Only one study provided data on MAT, precluding us from conducting a statistical analysis. The diagnostic accuracy of BAT was higher when stimulated with peanut extract rather than Ara h 2 with a pooled specificity of 96% (95% CI: 0.89-0.98) and sensitivity of 0.86 (95% CI: 0.74-0.93). The sensitivity and specificity of BATs in discriminating between allergic and sensitized patients were studied as well, with pooled analysis revealing a sensitivity of 0.86 (95% CI: 0.74; 0.93) and a specificity of 0.97 (95% CI: 0.94, 0.98). BATs, when stimulated with peanut extracts, exhibit a satisfactory sensitivity and specificity for the diagnosis of peanut allergy and can help to discriminate between allergic individuals and those only sensitized to peanuts. More investigations on the potential for MATs diagnostic methods are warranted.
Topics: Peanut Hypersensitivity; Humans; Sensitivity and Specificity; Basophils; Arachis; Child; Mast Cells; Basophil Degranulation Test; Allergens; Adult
PubMed: 38822743
DOI: 10.1111/pai.14140 -
Translational Pediatrics Mar 2024Eosinophilic esophagitis is a chronic inflammatory disorder, often relapsing. There is an increasing need to develop new alternative diagnostic and monitoring methods on... (Review)
Review
Eosinophilic esophagitis: absolute eosinophilic count, peak eosinophilic count, and potential biomarkers of eosinophilic degranulation products-an in-depth systematic review.
BACKGROUND
Eosinophilic esophagitis is a chronic inflammatory disorder, often relapsing. There is an increasing need to develop new alternative diagnostic and monitoring methods on a critical basis, which will provide samples through none or minimally invasive procedures. This study aims to identify and document the types and roles of potential biomarkers in eosinophilic esophagitis released by eosinophils as well as the potential relationship to the peak eosinophilic count and the degree of degranulation of eosinophils (DGE/DGE + NDGE: degranulated eosinophils/degranulated eosinophils and non-degranulated eosinophils).
METHODS
This is the first in-depth systematic review study using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) parameters involving a literature search of academic databases (PubMed, Scopus, Medline, Google Scholar, and Cochrane Database, 2011-2022) targeting specifically the eosinophilic counts and ratio, and the eosinophilic degranulation products as potential biomarkers. Data were extracted from ten selected studies and presented on a spreadsheet.
RESULTS
The studies show the ability to detect eosinophilic and non-eosinophilic degranulation products, and absolute eosinophilic count in samples, including blood and urine, thereby serving as potential surrogates in making the diagnosis or monitoring disease progression in the future. There is an obvious paucity of studies that correlate potential biomarkers to the degree of degranulation of eosinophils.
CONCLUSIONS
A few minimally invasive methods and biomarkers may be suggested as alternative tools in diagnosing and monitoring eosinophilic esophagitis. While there is no consensus on the clinical usefulness of these biomarkers, our critical evaluation may suggest that the eosinophilic degranulation ratio (DGE/DGE + NDGE: degranulated eosinophils/degranulated eosinophils and non-degranulated eosinophils) in the esophagus may be critical for evaluating properly these biomarkers. An increasing trend may culminate in the potential clinical use of these biomarkers evaluated not only with the peak eosinophilic count, but also with the degranulation score upon regulatory bodies' approval to monitor eosinophilic esophagitis in the future. We strongly advocate for the necessity to score the esophageal biopsies with both a peak eosinophilic count and a score of the degranulated eosinophils.
PubMed: 38590372
DOI: 10.21037/tp-23-478 -
Frontiers in Immunology 2024Anaphylaxis manifests as a severe immediate-type hypersensitivity reaction initiated through the immunological activation of target B-cells by allergens, leading to the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anaphylaxis manifests as a severe immediate-type hypersensitivity reaction initiated through the immunological activation of target B-cells by allergens, leading to the release of mediators. However, the well-known underlying pathological mechanisms do not fully explain the whole variety of clinical and immunological presentations. We performed a systemic review of proteomic and metabolomic studies and analyzed the extracted data to improve our understanding and identify potential new biomarkers of anaphylaxis.
METHODS
Proteomic and metabolomic studies in both human subjects and experimental models were extracted and selected through a systematic search conducted on databases such as PubMed, Scopus, and Web of Science, up to May 2023.
RESULTS
Of 137 retrieved publications, we considered 12 for further analysis, including seven on proteome analysis and five on metabolome analysis. A meta-analysis of the four human studies identified 118 proteins with varying expression levels in at least two studies. Beside established pathways of mast cells and basophil activation, functional analysis of proteomic data revealed a significant enrichment of biological processes related to neutrophil activation and platelet degranulation and metabolic pathways of arachidonic acid and icosatetraenoic acid. The pathway analysis highlighted also the involvement of neutrophil degranulation, and platelet activation. Metabolome analysis across different models showed 13 common metabolites, including arachidonic acid, tryptophan and lysoPC(18:0) lysophosphatidylcholines.
CONCLUSION
Our review highlights the underestimated role of neutrophils and platelets in the pathological mechanisms of anaphylactic reactions. These findings, derived from a limited number of publications, necessitate confirmation through human studies with larger sample sizes and could contribute to the development of new biomarkers for anaphylaxis.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024506246.
Topics: Humans; Anaphylaxis; Arachidonic Acid; Proteomics; Allergens; Biomarkers
PubMed: 38384462
DOI: 10.3389/fimmu.2024.1328212 -
Oncology 2024Patients with cancer receiving radio- or chemotherapy undergo many immunological stressors. Chronic regular exercise has been shown to positively influence the immune...
INTRODUCTION
Patients with cancer receiving radio- or chemotherapy undergo many immunological stressors. Chronic regular exercise has been shown to positively influence the immune system in several populations, while exercise overload may have negative effects. Exercise is currently recommended for all patients with cancer. However, knowledge regarding the effects of exercise on immune markers in patients undergoing chemo- or radiotherapy is limited. The aim of this study is to systematically review the effects of moderate- and high-intensity exercise interventions in patients with cancer during chemotherapy or radiotherapy on immune markers.
METHODS
For this review, a search was performed in PubMed and EMBASE, until March 2023. Methodological quality was assessed with the PEDro tool and best-evidence syntheses were performed both per immune marker and for the inflammatory profile.
RESULTS
Methodological quality of the 15 included articles was rated fair to good. The majority of markers were unaltered, but observed effects included a suppressive effect of exercise during radiotherapy on some pro-inflammatory markers, a preserving effect of exercise during chemotherapy on NK cell degranulation and cytotoxicity, a protective effect on the decrease in thrombocytes during chemotherapy, and a positive effect of exercise during chemotherapy on IgA.
CONCLUSION
Although exercise only influenced a few markers, the results are promising. Exercise did not negatively influence immune markers, and some were positively affected since suppressed inflammation might have positive clinical implications. For future research, consensus is needed regarding a set of markers that are most responsive to exercise. Next, differential effects of training types and intensities on these markers should be further investigated, as well as their clinical implications.
Topics: Humans; Neoplasms; Exercise; Killer Cells, Natural; Biomarkers; Exercise Therapy; Inflammation; Chemoradiotherapy
PubMed: 37793350
DOI: 10.1159/000534390 -
Journal of Clinical and Experimental... Jul 2023Oral submucous fibrosis (OSMF) is a chronic disorder associated with reduced mouth opening, burning sensation and listed as potentially malignant disorder. The role of... (Review)
Review
Oral submucous fibrosis (OSMF) is a chronic disorder associated with reduced mouth opening, burning sensation and listed as potentially malignant disorder. The role of mast cells in initiation and progression of this condition has been debated in last few years. It is imperative to understand the definitive role of mast cells and subsequently identify a possible cost-efficient treatment modality for OSMF. This review aimed to study the role of mast cells in OSMF by framing a research question that assessed the mast cell count (MCC), their degranulation and immunohistochemical analyses. We performed a comprehensive search of PubMed, EBSCOhost and general Google search that conceded 26 studies from which 15 articles were finalized for the review. The individual study syntheses revealed increased MCC in OSMF as compared to controls. Also, there was decreased MCC with the progression of OSMF. However, the metanalysis showed high level of heterogeneity as three studies out of eight studies found reduced MCC in disease when compared with controls. There is definite increase in mast cell in OSMF although the cell count falls with the advancement of OSMF. This increases the scope for further research to identify exact mechanism by which mast cells contribute to fibrosis and conduct the drug trials that can inhibit the mechanism. Oral submucous fibrosis, mast cell count, degranulated mast cells, stages of OSMF.Oral submucous fibrosis, mast cell count, degranulated mast cells, stages of OSMF.
PubMed: 37519326
DOI: 10.4317/jced.60234 -
Cancers Jun 2023Neutrophils are an important part of the tumor microenvironment, which stimulates inflammatory processes through phagocytosis, degranulation, release of small DNA... (Review)
Review
BACKGROUND
Neutrophils are an important part of the tumor microenvironment, which stimulates inflammatory processes through phagocytosis, degranulation, release of small DNA fragments (cell-free DNA), and presentation of antigens. Since neutrophils accumulate in peripheral blood in patients with advanced-stage cancer, a high neutrophil-to-lymphocyte ratio can be a biomarker of a poor prognosis in patients with glioblastoma. The present study aimed to explore the prognostic value of the preoperative levels of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), systemic inflammation response index (SIRI), and cell-free DNA (cfDNA) to better predict prognostic implications in the survival rate of glioblastoma patients.
METHODS
The meta-analysis was carried out according to the recommendations and standards established by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Databases of PubMed, EBSCO, and Medline were systematically searched to select all the relevant studies published up to December 2022.
RESULTS
Poorer prognoses were recorded in patients with a high NLR or PLR when compared with the patients with a low NLR or PLR (HR 1.51, 95% CI 1.24-1.83, < 0.0001 and HR 1.34, 95% CI 1.10-1.63, < 0.01, respectively). Similarly, a worse prognosis was reported for patients with a higher cfDNA (HR 2.35, 95% CI 1.27-4.36, < 0.01). The SII and SIRI values were not related to glioblastoma survival ( = 0.0533 and = 0.482, respectively).
CONCLUSIONS
Thus, NLR, PLR, and cfDNA, unlike SII and SIRI, appeared to be useful and convenient peripheral inflammatory markers to assess the prognosis in glioblastoma.
PubMed: 37444448
DOI: 10.3390/cancers15133339 -
The Journal of Allergy and Clinical... Aug 2023Chronic spontaneous urticaria (CSU) is believed to be Autoimmune (aiCSU) (type IIb CSU) in at least 8% of patients, associated with mast cell-activating IgG...
BACKGROUND
Chronic spontaneous urticaria (CSU) is believed to be Autoimmune (aiCSU) (type IIb CSU) in at least 8% of patients, associated with mast cell-activating IgG autoantibodies. Basophil tests such as the basophil activation test (BAT) and basophil histamine release assay (BHRA) are considered the best single tests for an aiCSU diagnosis. To date, the strength of associations among a positive BAT and/or BHRA (BAT/BHRA) and CSU features, patient demographics, and response to treatment remains poorly characterized.
OBJECTIVE
To evaluate the strength of current evidence on basophil tests as parameters for CSU characteristics.
METHODS
We performed a systematic literature search and review to assess the relationship between BAT/BHRA and clinical and laboratory parameters of CSU. Of 1,058 records found in the search, 94 studies were reviewed by experts in urticaria and 42 were included in the analysis.
RESULTS
In CSU patients, BAT/BHRA showed a strong level of evidence for an association with high disease activity and low levels of total IgE. A weak level of evidence was shown for the association of BAT/BHRA and the presence of angioedema, and basopenia.
CONCLUSIONS
Our results suggest that aiCSU defined by BAT/BHRA is more active or severe and is linked to other aiCSU markers such as low total IgE/basopenia. Basophil tests should be standardized and implemented in routine clinical care to improve the diagnosis and treatment of patients with aiCSU.
Topics: Humans; Basophils; Chronic Urticaria; Urticaria; Basophil Degranulation Test; Immunoglobulin E; Chronic Disease
PubMed: 37286132
DOI: 10.1016/j.jaip.2023.05.039 -
Archives of Gynecology and Obstetrics Jan 2024The immune system is influenced by many factors, including female sex hormones. The extent of this influence, however, is not completely understood so far. This... (Review)
Review
PURPOSE
The immune system is influenced by many factors, including female sex hormones. The extent of this influence, however, is not completely understood so far. This systematic literature review aims at giving an overview of the existing concepts on how endogenous progesterone influences the female immune system along the menstrual cycle.
METHODS
The inclusion criteria were healthy female subjects in their reproductive age with a regular menstrual cycle. The exclusion criteria were exogenous progesterone, animal models, nonhealthy study populations and pregnancy. This led to 18 papers covered in this review. The search was performed using the databases EMBASE, Ovid MEDLINE and Epub, and the last search was conducted on September 18, 2020. Our findings were analyzed in four categories: cellular immune defense, humoral immune defense, objective and subjective clinical parameters.
RESULTS
We demonstrated that progesterone acts in an immunosuppressive way, favoring a Th-2-like cytokine profile. Further, we showed that progesterone inhibits mast cell degranulation and relaxes smooth muscle cells. Furthermore, we found supporting evidence for a so-called window of vulnerability after ovulation, where immune functions are lowered and mediated through progesterone.
CONCLUSION
The clinical relevance of these findings is not completely understood yet. As the sample sizes of included studies were rather small and the content of them was broad, further investigations are needed to define to which extent the described changes actually clinically meaningful, whether they are capable of influencing the female health and how these findings can be used to increase well-being.
Topics: Female; Humans; Immune System; Menstrual Cycle; Ovulation; Progesterone; Reproduction
PubMed: 36933040
DOI: 10.1007/s00404-023-06996-9 -
Frontiers in Psychiatry 2022Cognitive decline is believed to be associated with neurodegenerative processes involving excitotoxicity, oxidative damage, inflammation, and microvascular and...
Cognitive decline is believed to be associated with neurodegenerative processes involving excitotoxicity, oxidative damage, inflammation, and microvascular and blood-brain barrier dysfunction. Interestingly, research evidence suggests upregulated synthesis of lipid signaling molecules as an endogenous attempt to contrast such neurodegeneration-related pathophysiological mechanisms, restore homeostatic balance, and prevent further damage. Among these naturally occurring molecules, palmitoylethanolamide (PEA) has been independently associated with neuroprotective and anti-inflammatory properties, raising interest into the possibility that its supplementation might represent a novel therapeutic approach in supporting the body-own regulation of many pathophysiological processes potentially contributing to neurocognitive disorders. Here, we systematically reviewed all human and animal studies examining PEA and its biobehavioral correlates in neurocognitive disorders, finding 33 eligible outputs. Studies conducted in animal models of neurodegeneration indicate that PEA improves neurobehavioral functions, including memory and learning, by reducing oxidative stress and pro-inflammatory and astrocyte marker expression as well as rebalancing glutamatergic transmission. PEA was found to promote neurogenesis, especially in the hippocampus, neuronal viability and survival, and microtubule-associated protein 2 and brain-derived neurotrophic factor expression, while inhibiting mast cell infiltration/degranulation and astrocyte activation. It also demonstrated to mitigate βamyloid-induced astrogliosis, by modulating lipid peroxidation, protein nytrosylation, inducible nitric oxide synthase induction, reactive oxygen species production, caspase3 activation, amyloidogenesis, and tau protein hyperphosphorylation. Such effects were related to PEA ability to indirectly activate cannabinoid receptors and modulate proliferator-activated receptor-α (PPAR-α) activity. Importantly, preclinical evidence suggests that PEA may act as a disease-modifying-drug in the early stage of a neurocognitive disorder, while its protective effect in the frank disorder may be less relevant. Limited human research suggests that PEA supplementation reduces fatigue and cognitive impairment, the latter being also meta-analytically confirmed in 3 eligible studies. PEA improved global executive function, working memory, language deficits, daily living activities, possibly by modulating cortical oscillatory activity and GABAergic transmission. There is currently no established cure for neurocognitive disorders but only treatments to temporarily reduce symptom severity. In the search for compounds able to protect against the pathophysiological mechanisms leading to neurocognitive disorders, PEA may represent a valid therapeutic option to prevent neurodegeneration and support endogenous repair processes against disease progression.
PubMed: 36387000
DOI: 10.3389/fpsyt.2022.1038122 -
Frontiers in Immunology 2022Chronic inducible urticaria (CIndU) constitutes a group of nine different CIndUs in which pruritic wheals and/or angioedema occur after exposure to specific and definite...
BACKGROUND
Chronic inducible urticaria (CIndU) constitutes a group of nine different CIndUs in which pruritic wheals and/or angioedema occur after exposure to specific and definite triggers. Histamine released from activated and degranulating skin mast cells is held to play a key role in the pathogenesis of CIndU, but evidence to support this has, as of yet, not been reviewed systematically or in detail. We aim to characterize the role and relevance of histamine in CIndU.
METHODS
We systematically searched 3 electronic databases (PubMed, Scopus, and Embase) for studies that reported increased serum or skin histamine concentration (direct evidence) or or histamine release (indirect evidence) following trigger exposure.
RESULTS
An initial total of 3,882 articles was narrowed down to 107 relevant studies of which 52 were in cold urticaria, 19 in cholinergic urticaria, 14 in heat urticaria, 10 in contact urticaria, 7 each in solar urticaria and vibratory angioedema, 4 each in symptomatic dermographism and aquagenic urticaria, and 3 in delayed pressure urticaria. The results of our review support that histamine has a key pathogenic role in the pathogenesis of all CIndUs, but it is not the sole mediator as evidenced by the often poor relationship between the level of histamine and severity of symptoms and the variable clinical efficacy of H-antihistamines.
CONCLUSIONS
Histamine released from skin mast cells is a key driver of the development of signs and symptoms and a promising therapeutic target in CIndU.
Topics: Angioedema; Chronic Urticaria; Histamine; Histamine Release; Humans; Urticaria
PubMed: 35967442
DOI: 10.3389/fimmu.2022.901851