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At least 19 recordsLinked to original sources

PubMed2005

[Vulvar contact dermatitis due to seminal allergy: 3 cases].

BACKGROUND: Contact sensitivity deserves to be assessed in acute vulvitis as well as chronic vulvar dermatitis with a specific orientation toward semen allergy whenever the pathology is post-coital. OBSERVATIONS: Three observations of semen allergy are reported. Two women presented with post-coital vulvitis due to delayed hypersensitivity to semen proteins without associated specific IgE. The type 2 allergy was confirmed by positive patch-tests and disappearance of symptoms when using condoms. Another woman presented with oedematous vulvitis associated with asthma and malaise per and post-sexual intercourse. Positive prick-tests with husband's semen and blood tests for specific IgE led to the diagnosis of type 1 hypersensitivity to semen, with disappearance of both vulvar and systemic symptoms with the use of condoms. DISCUSSION: Immediate or delayed type hypersensitivity may be discovered using prick and patch tests respectively. The observation of vulvitis or vulvar discomfort should promote such investigations, whenever a post-coital chronology is suggested. The good clinical pertinence of positive skin tests must be emphasized. Although type I hypersensitivity to semen is documented in the literature, with easy detection of specific IgE, delayed type 2 allergy presents as an as yet under-diagnosed etiology of post-coital vulvitis. Patch tests may help to confirm that contact dermatitis may be due to seminal proteins.

Acute Disease↗

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↗

PubMed2006

Different allele-distribution of mthfr 677 C -> T and mthfr -393 C -> a in patients classified according to subtypes of Lesch's typology.

AIMS: The typology by Lesch distinguishes between four subtypes: type 1 (model of allergy), type 2 (model of anxiety or conflict), type 3 (alcohol as an antidepressant), and type 4 (alcohol as adaptation). Taking into account that alcohol dependence is associated with elevated homocysteine levels, this study was undertaken to investigate different MTHFR (methylenetetrahydrofolate reductase) genotypes related to homocysteine metabolism in patients with alcohol dependence who were classified according to Lesch's typology (LT). SUBJECTS AND METHODS: 134 non-abstinent chronic alcoholics (112 males, 22 females; mean age 44.2 (SD 8.9) years) were classified according to LT and divided into four groups: LT 1 (n = 26), LT 2 (n = 65), LT 3 (n = 58), and LT 4 (n = 18). Total plasma homocysteine levels and MTHFR genotypes -393, 677, and 1,793 were determined. RESULTS: We observed a significantly higher frequency of the thermolabile MTHFR 677 C-->T variant (TT) in patients classified as subtype LT4 when compared with subtypes LT2 and LT3 (P = 0.005). Furthermore, for the MTHFR -393 C --> A-polymorphism, significantly more AC/AA variants were found in subtype LT4 (P = 0.034). No differences in allele-distribution were detected for MTHFR 1793. CONCLUSION: To our knowledge, this is the first study evaluating MTHFR genotypes in patients who were classified according to LT. Significantly different distributions of MTHFR 677 and -393 variants within Lesch Type 4 as compared with Types 2 and 3 hint at genetic determination of Lesch subtypes.

Adult↗

PubMed2006

Insulin allergy in a patient with Type 2 diabetes successfully treated with continuous subcutaneous insulin infusion.

BACKGROUND: Patients with poor control of Type 2 diabetes on maximum oral hypoglycaemic therapy invariably need insulin therapy. Insulin allergy is uncommon, particularly in patients with Type 2 diabetes. Management of the condition can be difficult, and here we report the case of a patient with Type 2 diabetes and insulin allergy successfully managed with a continuous subcutaneous insulin infusion (CSII). CASE REPORT: A 60-year-old man was referred with insulin allergy. He had poorly controlled Type 2 diabetes (glycated haemoglobin 10.4%), on maximum doses of sulphonylurea and metformin, with osmotic symptoms. He was compliant with diet and tablets. His diabetes was complicated by retinopathy, nephropathy, coronary heart disease, obstructive sleep apnoea, obesity, depression and hypertension. He commenced on twice daily mixed insulin and, shortly after, developed pain, itching and erythema at the injection sites. The sites became indurated and tender, and he had constitutional symptoms. The insulin was changed to other preparations, including short- and long-acting analogues, with similar responses. Triple therapy with rosiglitazone was tried, with no improvement in control. Skin-prick testing confirmed allergy to insulin rather than additives. The patient was reluctant to undergo desensitization. He was commenced on an insulin pump in addition to his oral hypoglycaemics, and achieved fair control (glycated haemoglobin 8.3%) on 88 units of lispro per day, with little or no skin or systemic reaction. CONCLUSION: This is the first case report of insulin allergy in Type 2 diabetes being successfully managed by CSII.

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↗

PubMed2002

Endotoxin, atopy and asthma.

Endotoxin is infamous for its ability to exacerbate existing allergy and asthma symptoms. Current research supports this phenomenon, demonstrating its significance in the home, as well as in the workplace. At the same time, evidence is emerging that exposure to endotoxin may drive immune development away from the T-helper lymphocyte type 2-mediated allergy and asthma profile. This fits in nicely with the 'hygiene hypothesis', which attributes the past century's rise in allergy and asthma to a reduction in microbial burden. Indeed, infections have been associated with less atopy and asthma. Recent investigations have suggested that naturally-occurring non-infectious exposure to microbial components such as endotoxin might mitigate atopy and asthma as well.

Air Pollution, Indoor↗

PubMed2005

Prevention of prescription errors by computerized, on-line surveillance of drug order entry.

AIMS: The present study was undertaken to quantify the impact of computerized drug order entry system (CDOE) connected to the patients' database, on the incidence and type of prescription errors (PEs) in the medical service, and to delineate the causes for remaining errors. METHODS: Drug orders were reviewed daily by a physician-reviewer, in a department of internal medicine that used for more than 3 years a CDOE (CDOEdept), and in a similar department in which drug orders were handwritten (HWdept). PEs were divided into those not related to the individual patient (type 1 PEs), and PEs resulting from drug-laboratory, drug-disease, and drug-allergy interactions (type 2 PEs). RESULTS: Ten thousand and two hospitalization days were evaluated. The incidence of type 1 PEs was 5.21 and 1.36 per 100 hospitalization days in the HWdept and CDOEdept, respectively (p<0.0001). Type 2 PEs were more common, 7.20 and 3.02 per 100 hospitalization days in the HWdept and CDOEdept, respectively (p<0.0001), and about 75% of them were due to few drug-laboratory interactions. Most of the remaining errors in the CDOEdept were due to inadequate adjustment of drugs and doses to renal function, or failure to perform adequate changes when new laboratory results became available. CONCLUSIONS: We conclude that linking the CDOE with few, specific, laboratory results has a large impact on the prevention of PEs. Combining the CDOE with a drug-laboratory alert system is expected to further reduce the incidence of PEs.

Academic Medical Centers↗

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↗

PubMed2001

Immediate-Type allergy against human insulin associated with marked eosinophilia in type 2 diabetic patient.

We describe a type 2 diabetic patient who showed immediate-type allergy against human insulin associated with marked eosinophilia at initial insulin therapy. Three months after initiation of insulin therapy, he noticed itchy skin wheals at the site of the insulin injection. Laboratory data at that time showed marked eosinophilia (2,512 /mm3) and progression of renal dysfunction. Skin test with semisynthetic human insulin and protamine sulfate resulted in local immediate skin reactions such as itchy erythema and wheals. Histopathology of the biopsy specimen from skin showed perivascular infiltration of lymphocytes and numerous eosinophils in the dermis and subcutaneous fat. Although the titer of total IgE antibody was within normal range, that of insulin-specific IgE antibody was high. Insulin administration was discontinued to preserve his insulin secretion, and stable control of his hyperglycemia was obtained by initiating nateglinide treatment (360 mg/day). His itchy skin lesions disappeared within two weeks after cessation of the insulin therapy and both eosinophilia and renal dysfunction gradually improved. Although the widespread use of human insulin in diabetic patients has greatly reduced the incidence of insulin allergy, the possibility of human insulin allergy should be kept in mind when initiating such therapy.

Aged↗

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↗

PubMed2006

Worms and allergy.

Worms and asthma are associated with a type 2 immune response, but evidence has accumulated that helminth infection is negatively associated with atopy, prevalence of allergic diseases and severity of asthma. One important difference between these polarized type 2 responses is that in allergy modulation of the immunological response is not appropriate, whereas in infection with helminths, several host mechanisms down-regulate the host immune response. As a result, patients infected with worms have a decrease in both type 1 and type 2 responses. The main mechanism involved in this down-modulation is increased production of IL-10, but expansion of regulatory T cells and NKT cells may also participate. Regarding the interaction between worms and allergy, a few variables need to be taken in account: phase (acute or chronic) of helminth infection, parasite load and species of helminth. In animals and humans, acute helminth infection may increase manifestations of allergy, whereas chronic infection with parasites decreases atopy. The modulation of the immune response by helminths is dependent on having an adequate parasite load. Moreover, although several helminth species have been shown to modulate immune responses, most in vitro and in vivo studies have focused on the importance of Schistosoma mansoni in down-modulating allergic reactions.

Animals↗

PubMed2005

Regulatory T cells as a target for induction of immune tolerance in allergy.

PURPOSE OF REVIEW: Reduced activity of regulatory T cells has recently been described in several diseases, including allergy. This concept of an alteration in the balance between the suppression and activation of harmful T helper type 2 immunity in allergy has important potential implications for strategies to prevent and control disease. RECENT FINDINGS: The past year has seen several important advances in analysing the determinants of this balance and models for inducing tolerance through regulatory T cells, including several different subtypes. These include the recognition that although T helper type 2 responses drive atopic sensitization, the expression of disease involves additional factors, and of a potential role for regulatory T cells in the development of neonatal tolerance. In addition to CD4CD25 regulatory T cells, experimental protocols for the induction of IL-10-producing, transforming growth factor beta and T helper type 1 regulatory T cells have been described in mouse models of airway disease. IL-6 and co-stimulation have been identified as potential determinants of the balance between the suppression and activation of allergic responses. SUMMARY: Different strategies for inducing regulatory T cells in animal models of allergic inflammation and an improved understanding of the factors accentuating or reducing suppression have identified important questions for future translational research.

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↗

PubMed2001

Cytokine expression profiles during murine contact allergy: T helper 2 cytokines are expressed irrespective of the type of contact allergen.

We have investigated the cytokine response pattern following sensitisation (induction) of BALB/c mice with different chemicals (dinitrochlorobenzene, dinitrofluorobenzene, oxazolone, glutaraldehyde, formaldehyde, trimellitic anhydride, croton oil) and elicitation (challenge) of contact allergy in sensitised animals. The results of our investigations showed that different chemicals induced both T helper (Th) 1 cytokines [interleukin (IL) 2, interferon beta (IFNgamma) [corrected] and Th2 cytokines (IL-4, IL-10) at different stages during murine contact allergy. We also confirmed our previous findings that IL-4 and IL-10 release were up-regulated during the challenge phase regardless the contact allergen used, whereas the release of IFNgamma [corrected] did not show a clear preference for being up- or down-regulated. In our hands, the increased expression of Th2 cytokines after challenge exposure to contact allergens appeared as a stable marker of secondary contact allergenic responses. Quantitative differences in the expression of IL-4 were observed between different contact allergens. The present results clearly indicate that skin sensitisers were able to elicit cytokine response patterns, which could not be related to a clear-cut Th1 or Th2 type of cytokine response. Furthermore, dermal application of contact allergens produced different kinetics of cytokine secretion upon induction and challenge. In our hands, the co-expression of Th1 and Th2 type cytokines appeared as a universal consequence of dermal application of contact allergens to responsive mice. Our results indicate that co-expression of Th1 and Th2 cytokines during contact allergy is an important feature of murine contact allergy in responsive mice and that chemicals differ in their potency to induce the expression of these cytokines. Furthermore, the results do not support the view that different chemicals induce Th1 or Th2 cytokines in a mutually exclusive manner depending on their preference for inducing either contact or respiratory allergy. The results are expected to renew the discussion about the usefulness of the Th1/Th2 paradigm in certain areas of immunotoxicology.

Allergens↗

PubMed2006

Effect of ACP1*C on early life viability.

Associations with past malarial morbidity, season of conception, and common diseases such as obesity, type 2 diabetes, and allergy argue against neutrality of the ACP1 genetic polymorphism. Comparison of ACP1 distribution in mothers and their newborns and analysis of the joint wife-husband ACP1 phenotype distribution in couples with repeated spontaneous abortion suggest a negative effect of the ACP1*C allele on early life viability. Analysis of the polymorphism of the ACP1 gene suggests that, unlike the ACP1*A and ACP1*B alleles, the ACP1*C allele is independent of sequences in the 5' flanking region, resulting in an inverted F/S isoform ratio.

Abortion, Spontaneous↗

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↗