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Nutrients Nov 2023Most adverse reactions to food are patient self-reported and not based on validated tests but nevertheless lead to dietary restrictions, with patients believing that... (Review)
Review
Most adverse reactions to food are patient self-reported and not based on validated tests but nevertheless lead to dietary restrictions, with patients believing that these restrictions will improve their symptoms and quality of life. We aimed to clarify the myths and reality of common food intolerances, giving clinicians a guide on diagnosing and treating these cases. We performed a narrative review of the latest evidence on the widespread food intolerances reported by our patients, giving indications on the clinical presentations, possible tests, and dietary suggestions, and underlining the myths and reality. While lactose intolerance and hereditary fructose intolerance are based on well-defined mechanisms and have validated diagnostic tests, non-coeliac gluten sensitivity and fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) intolerance are mainly based on patients' reports. Others, like non-hereditary fructose, sorbitol, and histamine intolerance, still need more evidence and often cause unnecessary dietary restrictions. Finally, the main outcome of the present review is that the medical community should work to reduce the spread of unvalidated tests, the leading cause of the problematic management of our patients.
Topics: Humans; Food Intolerance; Food Hypersensitivity; Quality of Life; Lactose Intolerance; Diet
PubMed: 38068827
DOI: 10.3390/nu15234969 -
JCI Insight Aug 2023Proline and its synthesis enzyme pyrroline-5-carboxylate reductase 1 (PYCR1) are implicated in epithelial-mesenchymal transition (EMT), yet how proline and PYCR1...
Proline and its synthesis enzyme pyrroline-5-carboxylate reductase 1 (PYCR1) are implicated in epithelial-mesenchymal transition (EMT), yet how proline and PYCR1 function in allergic asthmatic airway remodeling via EMT has not yet been addressed to our knowledge. In the present study, increased levels of plasma proline and PYCR1 were observed in patients with asthma. Similarly, proline and PYCR1 in lung tissues were high in a murine allergic asthma model induced by house dust mites (HDMs). Pycr1 knockout decreased proline in lung tissues, with reduced airway remodeling and EMT. Mechanistically, loss of Pycr1 restrained HDM-induced EMT by modulating mitochondrial fission, metabolic reprogramming, and the AKT/mTORC1 and WNT3a/β-catenin signaling pathways in airway epithelial cells. Therapeutic inhibition of PYCR1 in wild-type mice disrupted HDM-induced airway inflammation and remodeling. Deprivation of exogenous proline relieved HDM-induced airway remodeling to some extent. Collectively, this study illuminates that proline and PYCR1 involved with airway remodeling in allergic asthma could be viable targets for asthma treatment.
Topics: Animals; Mice; Airway Remodeling; Proline; Asthma; Lung; Hypersensitivity
PubMed: 37432745
DOI: 10.1172/jci.insight.167395 -
Nature Microbiology Oct 2023Alterations in the gut microbiome, including diet-driven changes, are linked to the rising prevalence of food allergy. However, little is known about how specific gut...
Alterations in the gut microbiome, including diet-driven changes, are linked to the rising prevalence of food allergy. However, little is known about how specific gut bacteria trigger the breakdown of oral tolerance. Here we show that depriving specific-pathogen-free mice of dietary fibre leads to a gut microbiota signature with increases in the mucin-degrading bacterium Akkermansia muciniphila. This signature is associated with intestinal barrier dysfunction, increased expression of type 1 and 2 cytokines and IgE-coated commensals in the colon, which result in an exacerbated allergic reaction to food allergens, ovalbumin and peanut. To demonstrate the causal role of A. muciniphila, we employed a tractable synthetic human gut microbiota in gnotobiotic mice. The presence of A. muciniphila within the microbiota, combined with fibre deprivation, resulted in stronger anti-commensal IgE coating and innate type-2 immune responses, which worsened symptoms of food allergy. Our study provides important insights into how gut microbes can regulate immune pathways of food allergy in a diet-dependent manner.
Topics: Humans; Mice; Animals; Verrucomicrobia; Food Hypersensitivity; Akkermansia; Immunoglobulin E
PubMed: 37696941
DOI: 10.1038/s41564-023-01464-1 -
The Journal of Clinical Investigation Aug 2023BACKGROUNDIgE-mediated anaphylaxis is a potentially fatal systemic allergic reaction for which there are no currently FDA-approved preventative therapies. Bruton's...
BACKGROUNDIgE-mediated anaphylaxis is a potentially fatal systemic allergic reaction for which there are no currently FDA-approved preventative therapies. Bruton's tyrosine kinase (BTK) is an essential enzyme for IgE-mediated signaling pathways and is an ideal pharmacologic target to prevent allergic reactions. In this open-label trial, we evaluated the safety and efficacy of acalabrutinib, a BTK inhibitor that is FDA approved to treat some B cell malignancies, in preventing clinical reactivity to peanut in adults with peanut allergy.METHODSAfter undergoing graded oral peanut challenge to establish their baseline level of clinical reactivity, 10 patients had a 6-week rest period, then received 4 standard doses of 100 mg acalabrutinib twice daily and underwent repeat food challenge. The primary endpoint was the change in patients' threshold dose of peanut protein to elicit an objective clinical reaction.RESULTSAt baseline, patients tolerated a median of 29 mg of peanut protein before objective clinical reaction. During subsequent food challenge on acalabrutinib, patients' median tolerated dose significantly increased to 4,044 mg (range 444-4,044 mg). 7 patients tolerated the maximum protocol amount (4,044 mg) of peanut protein with no clinical reaction, and the other 3 patients' peanut tolerance increased between 32- and 217-fold. 3 patients experienced a total of 4 adverse events that were considered to be possibly related to acalabrutinib; all events were transient and nonserious.CONCLUSIONAcalabrutinib pretreatment achieved clinically relevant increases in patients' tolerance to their food allergen, thereby supporting the need for larger, placebo-controlled trials.TRIAL REGISTRATIONClinicalTrials.gov NCT05038904FUNDINGAstraZeneca Pharmaceuticals, the Johns Hopkins Institute for Clinical and Translational Research, the Ludwig Family Foundation, and NIH grants AI143965 and AI106043.
Topics: Adult; Humans; Anaphylaxis; Agammaglobulinaemia Tyrosine Kinase; Benzamides; Pyrazines; Peanut Hypersensitivity; Allergens; Arachis
PubMed: 37384412
DOI: 10.1172/JCI172335 -
Biomedicine & Pharmacotherapy =... Aug 2023Combined allergic rhinitis and asthma syndrome (CARAS) causes chronic respiratory inflammation in allergic individuals. Long-term exposure to particulate matter 2.5...
Bergapten ameliorates combined allergic rhinitis and asthma syndrome after PM2.5 exposure by balancing Treg/Th17 expression and suppressing STAT3 and MAPK activation in a mouse model.
Combined allergic rhinitis and asthma syndrome (CARAS) causes chronic respiratory inflammation in allergic individuals. Long-term exposure to particulate matter 2.5 (PM2.5; particles 2.5 µm or less in diameter) can aggravate respiratory damage. Bergapten (5-methoxysporalen) is a furocoumarin mostly found in bergamot essential oil and has significant antioxidant, anticancer, and anti-inflammatory activity. This study created a model in which CARAS was exacerbated by PM2.5 exposure, in BALB/c mice and explored the potential of bergapten as a therapeutic agent. The bergapten medication increased ovalbumin (OVA)-specific immunoglobulin (Ig) G2a level in serum and decreased OVA-specific IgE and IgG1 expression. Clinical nasal symptoms diminished significantly, with weakened inflammatory reaction in both the nasal mucosa and lungs. Furthermore, bergapten controlled the T helper (Th)1 to Th2 ratio by increasing cytokines associated with Th1-like interleukin (IL)-12 and interferon gamma and decreasing the Th2 cytokines IL-4, IL-5, and IL-13. Factors closely related to the balance between regulatory T cells and Th17 (such as IL-10, IL-17, Forkhead box protein P3, and retinoic-related orphan receptor gamma) were also regulated. Notably, pro-inflammatory cytokines IL-6, IL-1β, and tumor necrosis factor-alpha were reduced by bergapten, which suppressed the activation of both the signal transducer and activator of transcription 3 signaling pathway and the mitogen-activated protein kinase signaling pathway. Therefore, bergapten might have potential as a therapeutic agent for CARAS.
Topics: Mice; Animals; 5-Methoxypsoralen; STAT3 Transcription Factor; T-Lymphocytes, Regulatory; Rhinitis, Allergic; Asthma; Inflammation; Cytokines; Particulate Matter; Ovalbumin; Mice, Inbred BALB C; Disease Models, Animal
PubMed: 37267637
DOI: 10.1016/j.biopha.2023.114959 -
Journal of Ayub Medical College,... 2023A multi-organ granulomatous disease with characteristic lung manifestations, sarcoidosis generally responds well to glucocorticoid therapy but 10% of cases are...
A multi-organ granulomatous disease with characteristic lung manifestations, sarcoidosis generally responds well to glucocorticoid therapy but 10% of cases are refractory necessitating immunosuppressive therapy. A 58-year-old lady presented with a dry cough and progressively worsening shortness of breath for the last 12 months. On investigation, her ESR was raised but cultures, malignancy screen and TB quantiferon were negative. HRCT chest demonstrated multiple pulmonary nodules with hilar lymphadenopathy and CT guided biopsy revealed non-caseating granuloma. She was diagnosed with Pulmonary Sarcoidosis and started on oral steroids with minimal improvement. Azathioprine was added but due to gastric intolerance switched to methotrexate. Her disease however continued to worsen and infliximab was started but she developed a severe allergic reaction. She was then started on mycophenolate mofetil but her chest imaging continued to worsen. After failing prednisone, azathioprine, methotrexate, infliximab and mycophenolate mofetil, the patient was started on rituximab.
Topics: Humans; Female; Middle Aged; Methotrexate; Infliximab; Mycophenolic Acid; Azathioprine; Sarcoidosis; Granuloma
PubMed: 38404097
DOI: No ID Found -
International Journal of Molecular... Mar 2024The basis of our current understanding of allergies begins with the discovery of IgE in the mid-1960s. The whole theory of the physiology and pathophysiology of allergic... (Review)
Review
The basis of our current understanding of allergies begins with the discovery of IgE in the mid-1960s. The whole theory of the physiology and pathophysiology of allergic diseases, including rhinitis and asthma, dates from that period. Among the key regions of IgE identified were the FAB (fragment antigen binding) portion that has the ability to capture allergens, and the Cε3 domain, through which IgE binds to its membrane receptor. It was then postulated that blocking IgE at the level of the Cε3 domain would prevent it from binding to its receptor and thus set in motion the allergic cascade. This was the beginning of the development of omalizumab, a monoclonal antibody with an anti-IgE effect. In this article, we review the pathophysiology of allergic disease and trace the clinical development of omalizumab. We also review the benefits of omalizumab treatment that are apparently unrelated to allergies, such as its effect on immunity and bronchial remodeling.
Topics: Humans; Omalizumab; Antibodies, Monoclonal, Humanized; Asthma; Hypersensitivity; Immunoglobulin E
PubMed: 38474304
DOI: 10.3390/ijms25053056 -
International Journal of Molecular... Sep 2023Allergic diseases, such as food allergies, asthma, and allergic rhinitis, continue to present a significant challenge for a broad cross-section of the population,...
Allergic diseases, such as food allergies, asthma, and allergic rhinitis, continue to present a significant challenge for a broad cross-section of the population, despite recent advancements in their treatment and prevention [...].
Topics: Humans; Prevalence; Rhinitis, Allergic; Asthma; Food Hypersensitivity
PubMed: 37762615
DOI: 10.3390/ijms241814312 -
Medical Science Monitor : International... Jan 2024The clinical association of purpura, arthralgia, and arthritis was first described in 1837 in a publication by Johann Lukas Schönlein, a German physician. In 1874,... (Review)
Review
The clinical association of purpura, arthralgia, and arthritis was first described in 1837 in a publication by Johann Lukas Schönlein, a German physician. In 1874, Eduard Henoch, a student of Schönlein, reported cases of children with purpura, abdominal pain, bloody diarrhea, and joint pain. IgA vasculitis, or Henoch-Schönlein purpura, is a systemic hypersensitivity vasculitis caused by the deposition of immune complexes in small blood vessels, including the renal glomeruli and mesangium. In the skin, the presentation is with non-thrombocytopenic purpura or urticaria. Worldwide, IgA nephropathy is the most common cause of primary glomerulonephritis. Detection of IgA deposition in small blood vessels and the renal glomeruli is diagnostic in most cases. This article aims to review the history, current classification, epidemiology, presentation, and diagnosis of IgA vasculitis and nephropathy, disease associations or trigger factors, including infections, vaccines, and therapeutic agents, and highlights some future approaches to improve diagnosis and clinical management.
Topics: Child; Humans; IgA Vasculitis; Immunoglobulin A; Glomerulonephritis, IGA; Vasculitis; Kidney Glomerulus; Hypersensitivity
PubMed: 38281080
DOI: 10.12659/MSM.943912 -
Nature Communications Aug 2023Allergic diseases affect millions of people worldwide. An increase in their prevalence has been associated with alterations in the gut microbiome, i.e., the...
Allergic diseases affect millions of people worldwide. An increase in their prevalence has been associated with alterations in the gut microbiome, i.e., the microorganisms and their genes within the gastrointestinal tract. Maturation of the infant immune system and gut microbiota occur in parallel; thus, the conformation of the microbiome may determine if tolerant immune programming arises within the infant. Here we show, using deeply phenotyped participants in the CHILD birth cohort (n = 1115), that there are early-life influences and microbiome features which are uniformly associated with four distinct allergic diagnoses at 5 years: atopic dermatitis (AD, n = 367), asthma (As, n = 165), food allergy (FA, n = 136), and allergic rhinitis (AR, n = 187). In a subset with shotgun metagenomic and metabolomic profiling (n = 589), we discover that impaired 1-year microbiota maturation may be universal to pediatric allergies (AD p = 0.000014; As p = 0.0073; FA p = 0.00083; and AR p = 0.0021). Extending this, we find a core set of functional and metabolic imbalances characterized by compromised mucous integrity, elevated oxidative activity, decreased secondary fermentation, and elevated trace amines, to be a significant mediator between microbiota maturation at age 1 year and allergic diagnoses at age 5 years (β = -2.28; p = 0.0020). Microbiota maturation thus provides a focal point to identify deviations from normative development to predict and prevent allergic disease.
Topics: Infant; Humans; Child; Gastrointestinal Microbiome; Hypersensitivity; Microbiota; Asthma; Dermatitis, Atopic
PubMed: 37644001
DOI: 10.1038/s41467-023-40336-4