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At least 19 recordsLinked to original sources
PubMed1995

A case of newly diagnosed non-insulin-dependent diabetes associated with immediate-type allergy against human insulin.

A case of newly diagnosed non-insulin-dependent diabetes mellitus with immediate-type allergy against semisynthetic human insulin is reported. She experienced immediate-type allergy 2 months after initial insulin treatment. A skin test showed that she had allergy against the insulin itself but not the additives. The amino acid sequence of the semisynthetic human insulin was identical to that of endogenous native insulin and, moreover, the patient had not been treated with animal-derived insulin previously, so a structural change to the semisynthetic formulation at the injected subcutaneous site might have antigenicity. An H1 histamine blocker markedly diminished the skin reaction to insulin, and her plasma glucose and glycosylated hemoglobin AIc became well controlled. In summary, we experienced a diabetic patient with human insulin allergy at the time of initial insulin treatment, emphasizing that the possibility of human insulin allergy should be considered whenever a patient is started on insulin therapy.

Diabetes Mellitus, Type 2↗
PubMed2026

Context-specific genetic effects inform endotypes and treatment in asthma.

BACKGROUND: Asthma has heterogeneous risk factors, subtypes, and treatments. It is often unclear how to stratify this heterogeneity in scientific studies and clinical care. Genetics could explain root causes of this clinical heterogeneity, called endotypes, but prior studies have used models that are not designed for complex diseases like asthma. OBJECTIVE: We aimed to find genetic effects that partly explain different asthma endotypes. METHODS: We used recent powerful and robust statistical models of context-specific genetic effects in complex traits. We identified genetic subtypes by clustering clinical asthma features in a case-control cohort, GALA II. We replicated the genetic endotypes in the UK Biobank with gene-context interaction tests. RESULTS: Asthma-associated single nucleotide polymorphisms, polygenic scores, and genome-wide heritability revealed subtype-specific genetic endotypes correlated with type 2 inflammation, allergy, and neuroticism. We validated the type 2 associations with molecular data including nasal RNA sequencing. In the UK Biobank, we replicated these endotypes and found they interact with several polygenic scores and drug-relevant genes. CONCLUSION: Our results show how context-specific genetic effects can unravel biomedically meaningful endotypes of complex disease and suggest novel precision treatment strategies.

Humans↗
PubMed2026

Prophylactic Inhaled Pattern Recognition Receptor Agonists Reprogram Lung Epithelial Response and Prevent Type 2 Allergic Inflammation.

Prophylactic inhalation of the synergistic agents ODN M362 and Pam2CSK4 ("Pam2ODN") protects mice against allergic lung disease, including allergic inflammation caused by house dust mite (HDM). By preventing sensitization, Pam2ODN reduces HDM-induced eosinophilic and lymphocytic inflammation. How Pam2ODN affects interactions among lung epithelial cells, dendritic cells, and T cells to prevent eosinophilic lung inflammation remains unclear. In the present study, we show that a single inhaled dose of Pam2ODN before HDM sensitization reduces airway Th2 polarization without affecting Th1 or Treg responses. Furthermore, Pam2ODN pretreatment inhibits the recruitment of lung monocyte-derived dendritic cells (moDCs) and conventional Type 2 dendritic cells (DC2s), while preventing the HDM-induced decrease in conventional Type 1 dendritic cells (DC1s). Bulk RNA-seq of the whole lung reveals that Pam2ODN pretreatment restricts the expression of proinflammatory transcripts induced by HDM sensitization. This tolerogenic effect is also reflected at the single-cell level in lung epithelial cells, where proinflammatory transcripts, pathways, and chromatin accessibility are inhibited. These results indicate that Pam2ODN reprograms lung epithelial cells to attenuate allergen-induced Th2-promoting cytokines and DCs while maintaining the population of protective DC1s. These findings suggest a strategy to mitigate chronic allergic lung diseases.

Animals↗
PubMed1994

Regulation of the development of type 2 T-helper cells in allergy.

In the last few years evidence has been accumulated to suggest that allergen-reactive type 2 T helper (Th2) cells play a triggering role in the activation and/or recruitment of IgE antibody-producing B cells, mast cells and eosinophils, the cellular triad involved in the allergic inflammation. Interleukin (IL)-4 production by a still unknown cell type (T-cell subset, mast cell/basophil?) at the time of antigen presentation to the Th cell is critical for the development of Th2 cells. Other cytokines, such as IL-1 and IL-10, and hormones, such as calcitriol and progesterone, also play a favoring role. In contrast, cytokines such as interferon-alpha, interferon-gamma, IL-12 and transforming growth factor-beta, and hormones, such as dehydroepiandrostenone, play a negative regulatory role in the development of Th2 cells. However, the mechanisms underlying the preferential activation by environmental allergens of Th2 cells in atopic subjects still remain obscure. Among the possibilities are alterations to molecular mechanisms directly involved in the regulation of IL-4 gene expression or deficient regulatory activity of cytokines that antagonize Th2 cells.

Allergens↗
PubMed1999

The paradigm of type 1 and type 2 antigen-presenting cells. Implications for atopic allergy.

Optimal clearance of the various pathogen types encountered by the human body requires the selective activation of particular cellular and/or humoral immune responses. The orchestration of the types of effector responses is directed by Th cells through the production of type 1 (Th1 cell-associated) and type 2 (Th2 cell-associated) cytokines. The way in which the Th cell cytokine profile is matched to the type of invading pathogen, and why these profiles sometimes derail and lead to disease, is not well understood. Here, we will discuss the concept that antigen-presenting cells (APC) provide Th cells not only with antigen and costimulatory signals, but also with a polarizing signal (signal 3). This signal can be mediated by many APC-derived factors, but IL-12 and PGE2 seem to be of major importance. The Th2-biased responses in atopic allergy appeared to be associated with monocytes with a decreased IL-12/PGE2 ratio and, consequently, with the down-regulation of type 1 cytokine production in Th cells. As for Th cells, APC can be functionialy polarized. In vitro experiments with monocyte-derived dendritic cells (DC) showed that the presence of IFN-gamma during activation of immature DC primes for mature DC with the ability of high IL-12 production and, consequently, a Th1-driving capacity (APC1 or DC1). In contrast, PGE2 primes for a low IL-12 production ability and a Th2-driving capacity (APC2 or DC2). These findings suggest that pathogens provoke either Th1- or Th2-cell development by inducing the production of a certain pattern of inflammatory DC-polarizing mediators (e.g. IFN-gamma and PGE2) at the site of infection. The type of immune polarization will not only depend on the type of pathogen, but also varies with the type of infected tissue, i.e. that different tissues produce different mediators in response to the same pathogen. In the case of atopic allergy, this concept implies that the Th2-cell bias may be related to low levels of cross-regulatory infections, to Th1 cell-inducing pathogens, or to an aberrant function of stromal cells in peripheral tissues.

Animals↗
PubMedDate not supplied

X-ray crystal structures of birch pollen profilin and Phl p 2.

BACKGROUND: Type 1 allergy affects 20% of industrialized populations and thus represents a major health care issue. The symptoms of type 1 allergy, which include rhinitis, conjunctivitis, dermatitis and asthma, are elicited by the cross-linking of IgE receptors through polyvalent allergens. A detailed understanding of the cell surface phenomena and the rational development of new therapies require high-resolution structural information. METHODS: The structures of two widespread allergens, birch pollen profilin (BPP) and Phl p 2 have been solved by multiple isomorphous replacement. Refinements are underway to 2.4 and 2.0 A, respectively. In addition, the IgE-reactive epitopes of BPP where identified by screening an epitope expression library with the serum IgE of an allergic individual. RESULTS: BPP exhibits an alpha/beta-fold which is similar to the mammalian and amoeba profilins. The structure of Phl p 2 is a compact eight-stranded beta-barrel. Screening an epitope library of BPP identified three major epitopic regions involved in IgE binding, including the amino and carboxy-terminal alpha-helices. These regions also interact with the physiologically relevant ligands of profilin, actin and proline-rich peptides. CONCLUSIONS: The distribution of IgE-binding sites on BPP allows for the productive interaction with IgE antibodies of different epitope specificities required for efficient signal transduction. These epitopes correspond to the most highly conserved regions of the profilin molecule and thus provide the molecular basis for allergen cross-sensitivity. Due to steric considerations, the involvement of these epitopic regions in the binding of physiologically relevant profilin ligands indicates that the native profilin is the species responsible for eliciting the allergic response. A comparison of the BPP and Phl p 2 structures shows that there is no preference for secondary structural elements in the allergic response. The detailed chemical and physical description of the major reactive epitopes provides a data base for the design of tight-binding monovalent ligands which can prevent receptor aggregation and thereby reduce the allergic response.

Allergens↗
PubMed1989

Allergic contact dermatitis from dental composite resins due to aromatic epoxy acrylates and aliphatic acrylates.

7 patients were occupationally sensitized to dental composite resin products (DCR): 6 dental nurses and 1 dentist. All had a positive patch test to their DCR. 2 independent types of allergy were seen; (a) aromatic epoxy acrylate, and/or (b) aliphatic acrylates. 4 out of 5 patients reacted to BIS-GMA, the most widely used aromatic epoxy acrylate in DCR, but not the dentist. She and 2 dental nurses were allergic to aliphatic acrylates, including triethylene glycol dimethacrylate (TREGDMA) and triethylene diglycol diacrylate (TREGDA). 4 patients were allergic to epoxy resin (ER) (containing mainly MW 340), possibly an impurity in some DCR. 2 patients were also allergic to methyl methacrylate (MMA): the dentist, had been exposed to MMA, but the nurse's exposure was uncertain. 1 patient was also allergic to rubber gloves, 2 to rubber chemicals but not their gloves, and 5 to disinfectants used. diagnosis was delayed as long as 13 years in spite of previous patch testing. Dermatologists need to use the patients' own DCR and the (meth)acrylate series for patch testing. No dental nurses could continue their occupation, but the dentist could occasionally handle DCR if wearing PVC gloves. Dental personnel need to know about the risks of DCR, and use no-touch techniques and protective gloves.

Acrylic Resins↗
PubMedDate not supplied

Positive allergological tests may turn negative with no further exposure to the specific allergen: a long-term, prospective, follow-up study in patients allergic to penicillin.

Preliminary literature reports suggest the possibility that, in an allergic patient, a previously positive allergological test may turn negative after a long period of time with no further exposure to the specific allergen. The aim of this study was to evaluate the rate by which a previously positive skin test or RAST may turn negative in a group of patients allergic to penicillin if no further exposure to the specific allergen occurs. Sixty-three patients allergic to penicillin (48 with type I allergy and 15 with type IV allergy) were enrolled in a long-term, prospective, follow-up study, undergoing a successive complete allergological testing within 6 years of the first positive examination. During the follow-up period, skin tests progressively became negative in 28 (58.3%) type I allergic patients and in only one (6.7%) subject with type IV allergy. Similarly, the positive RAST turned negative in as many as 13 subjects (43.3% of cases). The cumulative skin test positivity (type I allergy) was significantly lower than that of patch tests (type IV allergy) (chi 2 = 10.4; d.f. = 1; p < 0.005, Logrank test). No significant difference in the progressive rate of decrease in skin test and RAST cumulative positivity was observed in the 30 patients showing both RAST and skin test positivity on entering the follow-up study. Our results provide strong evidence that a positive allergological test performed in a drug-allergic patient may become negative with time, in the absence of further exposure to the specific antigen. A negative allergological test cannot, therefore, rule out the immunological basis of a drug sensitivity. This is why we always suggest advising patients with a personal history of drug hypersensitivity against any further administration of the responsible drug, even in the presence of a completely negative allergological examination.

Adolescent↗
PubMed2000

IL-13-mediated worm expulsion is B7 independent and IFN-gamma sensitive.

B7 costimulation is a required component of many type 2 immune responses, including allergy and protective immunity to many nematode parasites. This response includes elevations in Th2 cytokines and associated effector functions including elevations in serum IgG1 and IgE and parasite expulsion. In studies of mice infected with Trichuris muris, blocking B7 ligand interactions inhibited protective immunity, suppressed IL-4 production, and enhanced IFN-gamma production, but unexpectedly did not inhibit production of the Th2 cytokine, IL-13. Blocking both IFN-gamma and B7 restored protective immunity, which was IL-13 dependent, but did not restore IL-4 or associated IgE responses. Although IL-13 was required for worm expulsion in mice in which both IFN-gamma and B7 were blocked, IL-4 could mediate expulsion in the absence of both IL-13 and IFN-gamma. These studies demonstrate that 1) B7 costimulation is required to induce IL-4, but not IL-13 responses; 2) IL-13 is elevated in association with the IFN-gamma response that occurs following inhibition of B7 interactions, but can only mediate IL-4-independent protection when IFN-gamma is also inhibited; and 3) increased IL-13 production, in the absence of increased IL-4 production, is not associated with an IgE response, even in the absence of IFN-gamma.

Abatacept↗
PubMed1999

Constitutive activation of an epithelial signal transducer and activator of transcription (STAT) pathway in asthma.

Cytokine effects on immunity and inflammation often depend on the transcription factors termed signal transducers and activators of transcription (STATs), so STAT signaling pathways are candidates for influencing inflammatory disease. We reasoned that selective IFN responsiveness of the first STAT family member (Stat1) and Stat1-dependent immune-response genes such as intercellular adhesion molecule-1 (ICAM-1), IFN regulatory factor-1 (IRF-1), and Stat1 itself in airway epithelial cells provides a basis for detecting cytokine signaling abnormalities in inflammatory airway disease. On the basis of nuclear localization and phosphorylation, we found that epithelial Stat1 (but not other control transcription factors) was invariably activated in asthmatic compared with normal control or chronic bronchitis subjects. Furthermore, epithelial levels of activated Stat1 correlated with levels of expression for epithelial ICAM-1, IRF-1, and Stat1, and in turn, ICAM-1 levels correlated with T-cell accumulation in tissue. However, only low levels of IFN-gamma or IFN-gamma-producing cells were detected in airway tissue in all subjects. The results therefore provide initial evidence linking abnormal behavior of STAT pathways for cytokine signaling to the development of an inflammatory disease. In that context, the results also change the current scheme for asthma pathogenesis to one that must include a localized gain in transcriptional signal ordinarily used for a T helper 1-type cytokine (IFN-gamma) in combination with allergy-driven overproduction of T helper 2-type cytokines.

Asthma↗
PubMed1985

Occupational lung disease following long-term inhalation of pancreatic extracts.

Fourteen employees of a pharmaceutical company, who had been exposed to porcine pancreatic and other organic dusts for 1-18 years were examined because of exercise dyspnea and asthmatic attacks. Airway obstruction or bronchial hyperreactivity and disturbance of oxygen diffusion were present in all cases. Two patients showed evidence of acute alveolitis and 3 had radiological signs of mild fibrosis, whilst emphysema dominated in 7 others. Skin tests and bronchial provocation revealed hyperreactivity to pancreatic extracts. Pancreatic alpha-amylase was determined as a causative allergen for Type I allergy symptoms by means of RAST. Three pathomechanisms of the lung diseases are discussed: 1) Type I allergy of the airways to pancreatic enzymes, 2) broncho-alveolar Type III reaction to porcine proteins; and 3) proteolytic damage of the lung tissue and an increase of non-specific bronchial reactivity.

Amylases↗
PubMed1999

Genetic markers of atopy in infancy: results from the German Multicenter Allergy Study.

Genetic studies of atopy-associated traits require unambiguous phenotypes to avoid both type 1 and 2 errors. The German Multicenter Allergy Study has provided a birth cohort with longitudinally well defined and stable phenotypes. We summarize data on candidate gene studies on chromosomes 12q, 5q, and 13q using high total IgE and atopic dermatitis (AD) as the most common atopy associated phenotypes in early childhood. We also present data on a functional RANTES promoter polymorphism that we recently identified. A significantly higher frequency of the mutant allele was seen in individuals of African descent compared to Caucasian subjects. In addition, an association of the polymorphism with AD could be demonstrated in the MAS cohort. Although the statistical approaches are limited, the MAS cohort has provided a valuable population for candidate gene studies in atopy.

Chemokine CCL5↗
PubMed2025

DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.

BCL11B is a Cys2-His2 zinc-finger (C2H2-ZnF) domain-containing, DNA-binding, transcription factor with established roles in the development of various organs and tissues, primarily the immune and nervous systems. BCL11B germline variants have been associated with a variety of developmental syndromes. However, genotype-phenotype correlations along with pathophysiologic mechanisms of selected variants mostly remain elusive. To dissect these, we performed genotype-phenotype correlations of 92 affected individuals harboring a pathogenic or likely pathogenic BCL11B variant, followed by immune phenotyping, analysis of chromatin immunoprecipitation DNA-sequencing data, dual-luciferase reporter assays, and molecular modeling. These integrative analyses enabled us to define three clinical subtypes of BCL11B-related disorders. It is likely that gene-disruptive BCL11B variants and missense variants affecting zinc-binding cysteine and histidine residues cause mild to moderate neurodevelopmental delay with increased propensity for behavioral and dental anomalies, allergies and asthma, and reduced type 2 innate lymphoid cells. Missense variants within C2H2-ZnF DNA-contacting &#x3b1; helices cause highly variable clinical presentations ranging from multisystem anomalies with demise in the first years of life to late-onset, hyperkinetic movement disorder with poor fine motor skills. Those not in direct DNA contact cause a milder phenotype through reduced, target-specific transcriptional activity. However, missense variants affecting C2H2-ZnFs, DNA binding, and "specificity residues" impair BCL11B transcriptional activity in a target-specific, dominant-negative manner along with aberrant regulation of alternative DNA targets, resulting in more severe and unpredictable clinical outcomes. Taken together, we suggest that the phenotypic severity and variability is largely dependent on the DNA-binding affinity and specificity of altered BCL11B proteins.

Adolescent↗
PubMed1993

Contact allergies to topical corticosteroids.

The patient, a 34-year-old Japanese woman who noticed worsening of her rash after using topical corticosteroid preparations on her neck, was patch tested for both commercial preparations and corticosteroids themselves. The patch test results revealed that she had a contact allergy to gold, oxytetracycline, and 2 types of corticosteroid (acetonides and esters) in 7 compounds (betamethasone valerate and dipropionate, hydrocortisone butyrate and hydrocortisone butyrate propionate, amcinonide, budesonide, and fluocinonide).

Administration, Cutaneous↗
PubMed1993

The so-called 'allergic' nasal polyp.

A series of 95 consecutive patients who have had a polypectomy was investigated with regard to clinical history and the morphology of the polyps. The results were compared with a series of 203 patients with allergy, of whom 12 had been polypectomized. The study revealed that a high percentage of the 95 patients had subjective complaints, particularly nasal congestion, nasal discharge, sneezing, headache, snoring and a loss of smell. The latter was present in nearly 58% of the patients, and persisted long after the operation in a third of the cases. More than 50% of the 95 patients had had 3 or more polypectomies. Rather few patients suffered from allergy-like conditions. Eighty-two of the 95 polyps were of the ordinary, oedematous, eosinophilic type; 7 were neutrophilic, fibro-inflammatory; 5 showed pronounced hyperplasia of the seromucinous glands, and 1 was a so-called polyp with atypical stroma. Only 6% of the 203 patients with allergy had had a polypectomy. Ten of the 12 polyps removed from the series of patients with allergy were of the ordinary type and 2 of the fibro-inflammatory type. A review of the literature is done concerning the association between nasal polyp and different diseases. The results of the present study support the concept that allergy is not the only cause for nasal polyps and that the accumulation of eosinophilic granulocytes observed in most polyps is often not related to allergy.

Adult↗
PubMed1999

Executive summary of disease management of drug hypersensitivity: a practice parameter. Joint Task Force on Practice Parameters, the American Academy of Allergy, Asthma and Immunology, the American Academy of Allergy, Asthma and Immunology, and the Joint Council of Allergy, Asthma and Immunology.

Adverse drug reactions are a major health problem in the United States. About 25% of all adverse drug reactions have an allergic, pseudoallergic, or idiosyncratic/intolerant basis. Idiosyncratic drug reactions and drug intolerance are also included in this category. Drug allergy may be classified by the Gell and Coombs classification of human hypersensitivity (Type 1: IgE-mediated; Type 2: cytotoxic; Type 3: immune complex; and Type 4: cellular immune mediated). Drug allergy is also frequently characterized by the predominant tissue/organ involved (systemic, cutaneous, or visceral). To some extent, the structural characteristics of drugs and biologic products predict the type of hypersensitivity reaction.

Adverse Drug Reaction Reporting Systems↗
PubMed1993

Silent reading and secretory otitis media in school children.

In an unselected cohort of 366 8-year-old children, the relationship between secretory otitis media and reading achievement was investigated. The children underwent 10 impedance audiometries and 5 pure tone audiometries during their first year at school. At the beginning of the second grade they all had a Silent Reading Word Test (OS-400). The background parameters were recorded by an interview with one of the parents. There was a significant but small correlation between type B tympanograms in the first grade and silent word reading. No association between silent reading score and otological history or pure tone screening was found. In a stepwise multiple regression model, 37% of the variance could be 'explained' by the included variables. The 'classroom factor' could 'explain' about 17% of the variance, followed by phonology at the start of school (6%), gender (5%), social group of the mother (4%), type B tympanogram (2%), absence from school (2%) and allergy (1%).

Audiometry↗