The impact of structural integrity and route of administration on the antibody specificity against three cow's milk allergens - a study in Brown Norway rats

Research

Jeanette Lund Madsen, Stine Kroghsbo, Charlotte Bernhard Madsen, Irina Pozdnyakova,Vibeke Barkholt and Katrine Lindholm Bøgh

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Clinical and Translational Allergy 2014, 4:25  doi:10.1186/2045-7022-4-25

Published: 18 August 2014

Abstract (provisional)

Background

Characterisation of the specific antibody response, including the epitope binding pattern, is an essential task for understanding the molecular mechanisms of food allergy. Examination of antibody formation in a controlled environment requires animal models. The purpose of this study was to examine the amount and types of antibodies raised against three cow's milk allergens; beta-lactoglobulin (BLG), alpha-lactalbumin (ALA) and beta-casein upon oral or intraperitoneal (i.p.) administration. A special focus was given to the relative amount of antibodies raised against linear versus conformational epitopes.

Methods

Specific antibodies were raised in Brown Norway (BN) rats. BN rats were dosed either (1) i.p. with the purified native cow's milk allergens or (2) orally with skimmed milk powder (SMP) alone or together with gluten, without the use of adjuvants. The allergens were denatured by reduction and alkylation, resulting in unfolding of the primary structure and a consequential loss of conformational epitopes. The specific IgG1 and IgE responses were analysed against both the native and denatured form of the three cow's milk allergens, thus allowing examination of the relative amount of linear versus conformational epitopes.

Results

The inherent capacity to induce specific IgG1 and IgE antibodies were rather similar upon i.p. administration for the three cow's milk allergens, with BLG = ALA > beta-casein. Larger differences were found between the allergens upon oral administration, with BLG > ALA > beta-casein. Co-administration of SMP and gluten had a great impact on the specific antibody response, resulting in a significant reduced amount of antibodies. Together results indicated that most antibodies were raised against conformational epitopes irrespectively of the administration route, though the relative proportions between linear and conformational epitopes differed remarkably between the allergens.

Conclusions

This study showed that the three-dimensional (3D) structure has a significant impact on the antibodies raised for both systemic and orally administered allergens. A remarkable difference in the antibody binding patterns against linear and conformational epitope was seen between the allergens, indicating that the structural characteristics of proteins may heavily affect the induced antibody response.

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Contact urticaria syndrome caused by haptens

Postepy Dermatol Alergol. May 2014; 31(2): 108–112.

Published online Apr 22, 2014. doi:  10.5114/pdia.2014.40915

PMCID: PMC4112244

Krzysztof Gomułka and Bernard Panaszek

Abstract:

In the group of urticaria, contact urticaria syndrome is a particular variety. In these patients, appearance of typical skin lesions is preceded by contact of the skin and mucous membranes with various inhaled allergens, nutrients or contact details. Furthermore, symptoms connected with contact urticaria syndrome are characterized by gradual, stepwise waveform, which can be easily generalized – patients may develop systemic symptoms similar to those found in the angioedema, asthma or anaphylactic shock. It is an attribute of contact urticaria syndrome in the course of which potentially life-threatening symptoms may develop after contact of the skin with the allergen. The underlying mechanisms are poorly understood; both immunological and non-immunological mechanisms are taken into account, therefore contact urticaria syndrome can be classified into two categories – allergic and non-allergic. An intriguing phenomenon seems to be the immediate reaction after exposure to low molecular weight allergens – haptens, such as metals, which are usually the cause of delayed allergic reactions. Diagnosis is based on clinical presentation indicating a coincidence of the onset of allergy with contract with allergen, and helpful exposure tests. Treatment consists of supportive antihistamines and corticosteroids – locally and systemically. In the case of anaphylaxis, appropriate treatment intensification of the integration of pressor amines and hydration is necessary. It is also regarded that prevention is advisable, which consists of relevant information to avoid situations connected with contact with well-known factors. In this paper we describe a case of a 57-year-old female admitted to the Department of Internal Medicine, Geriatrics and Allergology, Medical University in Wroclaw to undergo diagnostic tests of chronic urticaria and angioedema. According to information obtained from the clinical presentation and after the diagnostic procedures, contact urticaria syndrome due to exposure to metals was diagnosed.

Keywords: contact urticaria syndrome, haptens, immediate contact reaction

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Impact of air pollution on respiratory diseases in children with recurrent wheezing or asthma

Research article

Susanna Esposito^1*, Carlotta Galeone², Mara Lelii¹, Benedetta Longhi¹, Beatrice Ascolese¹, Laura Senatore¹, Elisabetta Prada¹, Valentina Montinaro¹, Stefano Malerba³,Maria Francesca Patria¹ and Nicola Principi¹

• *Corresponding author: Susanna Esposito susanna.esposito@unimi.it

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BMC Pulmonary Medicine 2014, 14:130  doi:10.1186/1471-2466-14-130

Published: 7 August 2014

Abstract

Background

Air pollution has many negative health effects on the general population, especially children, subjects with underlying chronic disease and the elderly. The aims of this study were to evaluate the effects of traffic-related pollution on the exacerbation of asthma and development of respiratory infections in Italian children suffering from asthma or wheezing compared with healthy subjects and to estimate the association between incremental increases in principal pollutants and the incidence of respiratory symptoms.

Methods

This prospective study enrolled 777 children aged 2 to 18 years (375 with recurrent wheezing or asthma and 402 healthy subjects). Over 12 months, parents filled out a daily clinical diary to report information about respiratory symptoms, type of medication used and healthcare utilization. Clinical data were combined with the results obtained using an air pollution monitoring system of the five most common pollutants.

Results

Among the 329 children with recurrent wheezing or asthma and 364 healthy subjects who completed follow-up, children with recurrent wheezing or asthma reported significantly more days of fever (p = 0.005) and cough (p - 0.001), episodes of rhinitis (p = 0.04) and tracheitis (p = 0.01), asthma attacks (p - 0.001), episodes of pneumonia (p - 0.001) and hospitalizations (p = 0.02). In the wheezing/asthma cohort, living close to the street with a high traffic density was a risk factor for asthma exacerbations (odds ratio [OR] = 1.79; 95% confidence interval [CI], 1.13-2.84), whereas living near green areas was found to be protective (OR = 0.50; 95% CI, 0.31 -0.80). An increase of 10 μg/m³ of particulates less than 10 microns in diameter (PM₁₀) and nitrogen dioxide (NO₂) increased the onset of pneumonia only in wheezing/asthmatic children (continuous rate ratio [RR] = 1.08, 95% CI: 1.00-1.17 for PM₁₀; continuous RR = 1.08, 95% CI: 1.01-1.17 for NO₂).

Conclusions

There is a significant association between traffic-related pollution and the development of asthma exacerbations and respiratory infections in children born to atopic parents and in those suffering from recurrent wheezing or asthma. These findings suggest that environmental control may be crucial for respiratory health in children with underlying respiratory disease.

Keywords: 

Air pollution; Asthma; NO₂; PM₁₀; Respiratory disease; Traffic-related pollutant; Wheezing 

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Bitter Taste Receptors in The Wrong Place: Novel Airway Smooth Muscle Targets For Treating Asthma

Trans Am Clin Climatol Assoc. 2014;125:64-75.

Liggett SB.

• Tampa, Florida.

Abstract

There is a need to expand the classes of drugs used to treat obstructive lung diseases to achieve better outcomes. With only one class of direct bronchodilators (β-agonists), we sought to find receptors on human airway smooth muscle (ASM) that act via a unique mechanism to relax the muscle, have a diverse agonist binding profile to enhance the probability of finding new therapeutics, and relax ASM with equal or greater efficacy than β-agonists. We have found that human and mouse ASM express six bitter taste receptor (TAS2R) subtypes, previously thought only to exist in taste buds of the tongue. Agonists acting at TAS2Rs evoke profound bronchodilation via a Ca(2+)-dependent mechanism. TAS2R function is not altered in asthma models, undergoes minimal tachyphylaxis upon repetitive dosing, and relaxes even under extreme desensitization of relaxation by β-agonists. Taken together, TAS2Rs on ASM represent a novel pathway to consider for development of agonists in the treatment of asthma and chronic obstructive lung disease.

PMID:

 

25125719

 

[PubMed - in process] 

PMCID:

 

PMC4112707

 

Respiratory symptoms and pulmonary function tests in security and safety products plant workers

Int J Clin Exp Med. 2014 Jul 15;7(7):1883-6. eCollection 2014.

Balbay EG, Toru U, Arbak P, Balbay O, Suner KO, Annakkaya AN

Abstract

OBJECTIVE:

Lock and key factory workers are under the risk of metal pneumoconiosis and occupational asthma. In this cross-sectional study, it's aimed to evaluate the relationship between metal dust exposure and respiratory symptoms, pulmonary function tests of workers in different section of lock and key factory.

METHODS:

54 male workers (mean age, 32.8 ± 5.4) in a security and safety products plant were evaluated for respiratory symptoms, pulmonary function tests and smoking habits. Results have been interpreted by comparison of the painting (28/54) and grinding group workers (26/54).

RESULTS:

There was no significant difference between painting (32.1 ± 4.8) and grinding (33.6 ± 6.1) groups regarding mean age (P > 0.05). Smokers were in significantly higher in grinding group (18/26). Cough and sputum were reported 14.3% (4/28) in painting and 3.8% (1/26) in grinding workers (P > 0.05). Chest tightness was seen in 7.1% and 7.7% of painting and grinding workers, respectively (P > 0.05). But no chest tightness was reported in both groups when they were away work. Breathlessness was seen in 10.7% and 7.7% of painting and grinding workers, respectively (P > 0.05). Breathlessness was similar in both groups (7.1% vs. 3.8%) when they were away work. When comparing painting and grinding workers respiratory functions no significant difference observed. Chest radiography in painting and grinding workers showed hyperlucency (3.6% vs.11.4%), respectively.

CONCLUSION:

Painting groups in lock and key factory workers had more but statistically insignificant respiratory complaints. Interestingly, chest tightness was only observed when both groups were at work. It was thought that ventilation and using personal protective equipment in factory could provide significant benefits.

KEYWORDS:

Lock and key factory workers; respiratory functions; respiratory symptoms

PMID:

 

25126195

 

[PubMed] 

PMCID:

 

PMC4132159

 

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Microbiota in Healthy Skin and in Atopic Eczema

Biomed Res Int. 2014;2014:436921. Epub 2014 Jul 13.

Baviera G, Leoni MC, Capra L, Cipriani F, Longo G, Maiello N, Ricci G, Galli E.

Abstract

The Italian interest group (IG) on atopic eczema and urticaria is member of the Italian Society of Allergology and Immunology. The aim of our IG is to provide a platform for scientists, clinicians, and experts. In this review we discuss the role of skin microbiota not only in healthy skin but also in skin suffering from atopic dermatitis (AD). A Medline and Embase search was conducted for studies evaluating the role of skin microbiota. We examine microbiota composition and its development within days after birth; we describe the role of specific groups of microorganisms that colonize distinct anatomical niches and the biology and clinical relevance of antimicrobial peptides expressed in the skin. Specific AD disease states are characterized by concurrent and anticorrelated shifts in microbial diversity and proportion of Staphylococcus. These organisms may protect the host, defining them not as simple symbiotic microbes but rather as mutualistic microbes. These findings reveal links between microbial communities and inflammatory diseases such as AD and provide novel insights into global shifts of bacteria relevant to disease progression and treatment. This review also highlights recent observations on the importance of innate immune systems and the relationship with normal skin microflora for the maintenance of healthy skin.

PMID: 25126558 [PubMed - as supplied by publisher] PMCID: PMC4122000

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The Association between Platelet Count and Acute Phase Response in Chronic Spontaneous Urticaria

Biomed Res Int. 2014;2014:650913. doi: 10.1155/2014/650913. Epub 2014 Jun 16.

Kasperska-Zając A, Grzanka A, Jarzab J, Misiołek M, Wyszyńska-Chłap M, Kasperski J, Machura E.

Abstract

Background. The platelet parameters and C-reactive protein (CRP) are markers reflecting a systemic inflammatory response. Among those, CRP is one of the major proteins helpful in determination of severity/activity of chronic spontaneous urticaria (CSU). Aim. To determine relationships between platelet activation indices and serum concentration of CRP, the best marker of acute phase response, and their potential clinical use in CSU patients.

Methods. Mean platelet volume (MPV), platelet distribution width (PDW), and platelet count as well as serum CRP concentration were measured in CSU patients, showing different degrees of urticarial severity, and in the healthy subjects.

Results. No significant differences were found in MPV and PDW between CSU group and the healthy subjects. The platelet count was significantly higher in moderate-severe CSU than that of the controls and mild CSU patients. Serum CRP concentrations were significantly higher in CSU patients as compared with the healthy subjects and significantly correlated with the platelet count in CSU patients.

Conclusions. Acute phase response in CSU is associated with the increased number of circulating platelets in patients with more severe symptoms. It seems that simple determination of platelet size indices is not a reliable indicator of CSU severity/activity.

PMID: 25025065 [PubMed - in process] PMCID: PMC4084584 

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Pathogenesis of chronic urticaria: an overview

Dermatol Res Pract. 2014;2014:674709. doi: 10.1155/2014/674709. Epub 2014 Jul 10.

Jain S.

Author information

• Skin Care Clinic, 108 Darya Ganj, New Delhi 110002, India.

Abstract

The pathogenesis of chronic urticaria is not well delineated and the treatment is palliative as it is not tied to the pathomechanism. The centrality of mast cells and their inappropriate activation and degranulation as the key pathophysiological event are well established. The triggering stimuli and the complexity of effector mechanisms remain speculative. Autoimmune origin of chronic urticaria, albeit controversial, is well documented. Numerical and behavioral alterations in basophils accompanied by changes in signaling molecule expression and function as well as aberrant activation of extrinsic pathway of coagulation are other alternative hypotheses. It is also probable that mast cells are involved in the pathogenesis through mechanisms that extend beyond high affinity IgE receptor stimulation. An increasing recognition of chronic urticaria as an immune mediated inflammatory disorder related to altered cytokine-chemokine network consequent to immune dysregulation resulting from disturbed innate immunity is emerging as yet another pathogenic explanation. It is likely that these different pathomechanisms are interlinked rather than independent cascades, acting either synergistically or sequentially to produce clinical expression of chronic urticaria. Insights into the complexities of pathogenesis may provide an impetus to develop safer, efficacious, and targeted immunomodulators and biological treatment for severe, refractory chronic urticaria.

PMID:

 

25120565

 

[PubMed] 

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Food allergy: Diagnosis, management & emerging therapies

Indian J Med Res. 2014 Jun;139(6):805-13.

Robison RG.

Author information

Abstract

IgE-mediated food allergy is an important health concern with increasing prevalence worldwide. Manifestations of IgE-mediated food allergy include urticaria, angioedema, pruritus, difficulty in breathing, laryngeal oedema, vomiting, diarrhoea and/or hypotension within minutes to two hours of the offending food's ingestion. Diagnosis requires both a careful history and supportive testing with laboratory studies and possibly oral food challenges. Current treatment of food allergy focuses on avoidance of the allergen and prompt emergency management of reactions. Epinephrine autoinjectors are provided to patients for the treatment of severe reactions. More research is needed to determine the optimal timing with which to introduce common allergens into a child's diet to possibly prevent the development of food allergy. Novel therapies are under investigation given the difficulty of allergen avoidance and the potentially fatal nature of reactions. Both allergen specific therapies such as oral, sublingual and epicutaneous immunotherapy and allergen non-specific therapies such the Chinese herbal formula FAHF-2 and omalizumab show promise though more data on efficacy and long-term safety are needed before these therapies become mainstream.

PMID:

 

25109714

 

[PubMed - in process] 

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Allergy to lidocaine injections: comparison of patient history with skin testing in five patients

abstract:

Original paper

Dorota Jenerowicz, Adriana Polańska, Olga Glińska, Magdalena Czarnecka-Operacz, Robert A. Schwartz

Postep Derm Alergol 2014; XXXI, 3: 134–138

DOI (digital object identifier): 10.5114/pdia.2014.40937

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Introduction: True allergy to local anesthetics, especially lidocaine, is uncommon. Most adverse reactions to this group of medications are classified as psychomotor, autonomic or toxic. In the case of suspected hypersensitivity to local anesthetics, skin testing is considered to be a useful tool – patch tests and intradermal tests for delayed hypersensitivity and skin prick tests and intradermal tests for immediate reactions. There is a particular need for such a diagnostic procedure, as patients suspected of hypersensitivity to local anesthetic drugs are frequently admitted.

Aim: To highlight the problem of hypersensitivity to local anesthetics on the basis of authors' own experience and literature data.

Material and methods: We present cases of 5 patients referred to the clinic by their dentists with a suspicion of allergy to local anesthetics, four to lidocaine and 1 to articaine.

Results: Intradermal tests were positive in 1 out of 5 subjects, with a concomitant episode of urticaria. In 1 patient we obtained a doubtful result of intradermal tests. Skin prick tests and patch tests were negative in all cases. In 2 cases we performed an incremental challenge test also with a negative result.

Conclusions: It has to be emphasized that, although rare, consequences of true allergy to local anesthetics can be serious considering a patient’s future management and therapy. That is why this diagnosis may be crucial.

keywords:

lidocaine, skin tests, incremental challenge test

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Cardiovascular safety of antihistamines

Review paper

Anna Olasińska-Wiśniewska, Jerzy Olasiński, Stefan Grajek

Postep Derm Alergol 2014; XXXI, 3: 182–186

DOI (digital object identifier): 10.5114/pdia.2014.43191

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Histamine is a mediator, which increases the permeability of capillaries during the early phase of allergic reaction, causes smooth muscle contraction of bronchi and stimulates mucous glands in the nasal cavity. Antihistamines are the basis of symptomatic treatment in the majority of allergic diseases, especially allergic rhinitis, allergic conjunctivitis, urticaria and anaphylaxis. The cardiotoxic effects of the two withdrawn drugs, terfenadine and astemizole, were manifested by prolonged QT intervals and triggering torsades de pointes (TdP) caused by blockade of the ‘rapid’ IKr potassium channels. These phenomena, however, are not a class effect. This review deals with a new generation of antihistamine drugs in the context of QT interval prolongation risk.

keywords:

histamine, H1 receptor, antihistamines, QT interval, torsades de pointes

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Night-time sedating H1-antihistamine increases daytime somnolence but not treatment efficacy in chronic spontaneous urticaria: a randomized controlled trial

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British Journal of Dermatology

Volume 171, Issue 1, pages 148–154, July 2014

M. Staevska, M. Gugutkova, C. Lazarova, T. Kralimarkova, V. Dimitrov, T. Zuberbier, M.K. Church, and T.A. Popov

Summary

Background

Many physicians believe that the most effective way to treat chronic urticaria is to take a nonsedating second-generation H1-antihistamine in the morning and a sedating first-generation H1-antihistamine, usually hydroxyzine, at night to enhance sleep. But is this belief well founded?

Objectives

To test this belief by comparing the effectiveness and prevalence of unwanted sedative effects when treating patients with chronic spontaneous urticaria (CSU) with levocetirizine 15 mg daily plus hydroxyzine 50 mg at night (levocetirizine plus hydroxyzine) vs. levocetirizine 20 mg daily (levocetirizine monotherapy).

Methods

In this randomized, double-blind, cross-over study, 24 patients with difficult-to-treat CSU took levocetirizine plus hydroxyzine or levocetirizine monotherapy for periods of 5 days each. At the end of each treatment period, assessments were made of quality of life (Chronic Urticaria Quality of Life Questionnaire, CU-Q2oL), severity of urticaria symptoms (Urticaria Activity Score, UAS), sleep disturbance during the night and daytime somnolence.

Results

Both treatments significantly decreased UAS, night-time sleep disturbances and CU-Q2oL scores (P < 0·001) without significant differences between the two. Compared with baseline, daytime somnolence was significantly reduced by levocetirizine monotherapy (P = 0·006) but not by levocetirizine plus hydroxyzine (P = 0·218). Direct comparison of the two treatment modalities in terms of daytime somnolence favoured levocetirizine monotherapy (P = 0·026).

Conclusions

The widespread belief that sleep is aided by the addition of a sedating first-generation H1-antihistamine, usually hydroxyzine, at night is not supported. These results are in line with the urticaria guidelines, which state that first-line treatment for urticaria should be new-generation, nonsedating H1-antihistamines only.

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