After the work of J. Benveniste, who had, in the 70s-80s, discovered the Platelet Activating Factor (PAF) and showed its role in the manifestations of Allergy, this chemical mediator formed de novo in the context of allergic inflammation had been eclipsed by other arachidonic acid-derived phospholipids. Now, a Canadian group from Toronto brings back attention to it by reminding us of its importance and by studying its concentration in human cases of Anaphylaxis, ( P.Vadas et al : Platelet Activating Factor, PAF Acétylhydrolase and severe anaphylaxis NEJM 2008 358 28-35)
This study comprised 2 parts : in the first part, the authors measured the concentration of PAF and that of its inactivation enzyme PAF-acethylhydrolase in 41 patients (15 to 74 years old ; 26 female, 15 male) with severe anaphylaxis (grades 1, 2, and 3 according to the severity of symptoms). Anaphylaxis was due to food allergy in 22 cases, to drugs in 12 cases , to hymenoptera stings in 2 cases. Twenty three volunteers were used as controls.
Serum PAF levels were significantly higher in patients (805pg ± 595/ml) than in controls (127±104pg/ml) and correlated with the severity of anaphylaxis (20% in group 1, 71% in group 2, and 100% in group 3). An inverse correlation was seen between serum levels of PAF and PAF-acethylhydrolase. The latter levels were also negatively correlated with symptom severity.
In a second part of the study, the authors measured serum levels of PAF-acethylhydrolase in nine children and young adults that had died of Anaphylaxis due to peanut allergy (in comparison with 5 varied groups of controls). This analysis was also carried out in 2 groups of asthmatic children, 15 patients with severe asthma under risk of death as well as in 19 patients with moderately severe asthma. Serum levels were extremely low in all cases of mortal Anaphylaxis, as compared to all the other groups (including the cases of asthma) suggesting that the absence of inactivation of PAF might contribute towards the increased severity of Anaphylaxis.
It should be underlined that administration of adrenalin or corticosteroids did not have any effect upon the serum levels of the enzyme.
Thus, PAF is rehabilitated as a potent mediator as well as a bio-marker of Allergy and, in particular, Anaphylaxis.
One must regret, however, that no mention is made of the countless French studies in this field.
Allergy to mammalian (mainly cow, goat, ewe) milk is one of the earliest manifestations of IgE-dependent food allergy, affecting about 2.5 % of children under the age of 3. Although most of these children will spontaneously become tolerant to milk, this type of allergy will remain in 10% of them, and will be associated with multiple manifestations : gastro-intestinal, respiratory, cutaneous and systemic.
Several reports have showed that milk-allergic patients may be more prone to develop an early sensitisation to maternal milk (MM) proteins at the same time that they develop a sensitisation to food allergens.
Recently, a case of contact urticaria to MM has been described in the literature, demonstrating the possibility of a clinical expression of such sensitisation.
These aspects drove Schulmeister U. et al (in a european multicentre study involving the University Hospital of Strasbourg) to study the specificity and biological pertinence of IgE reactivity against MM antigens in cow’s milk (CM)-allergic patients (Sensitization to human milk. Clin Exp Allergy. 2008 Jan;38(1):60-8).
The reactivity of IgE specific to CM proteins as well as to MM proteins was analysed using immunoblots performed on 21 serum samples from CM-allergic children and adults, whereas IgE cross-reactivity between CM and MM antigens was studied by immunoblot inhibition. Serum samples taken from a non milk-allergic population were used as controls.
Analyses of samples from genetically unrelated mothers, performed before and after the administration of milk products showed that the reactivity of IgE against MM proteins was neither due to alloreactivity nor to the introduction of foreign antigens in the maternal milk.
Its biological pertinence was confirmed by skin prick tests, which were positive in 80 % of cow’s milk-allergic individuals, in relation or not to a cross-reaction with α-lactalbumine.
The results of this study show that an IgE-mediated sensitisation to maternal milk, either real or due to a cross-reaction, is possible and may underlie clinical manifestations. It is frequent in individuals with food allergy to milks of animal origin, particularly cow’s milk.
After the first Japanese studies on the adjuvant role of diesel particules in pollen allergy, a good number of epidemiological or experimental papers focusing on the effects of car-related air pollution on the respiratory system.
The originality of the recent study by english authors (J. McCreanor et al Respiratory effects of exposure to diesel traffic in persons with asthma : NEJM 2007 357 2348-58 ) has to do with the fact that they studied the short term effects, both functional and immunological, of a 2 hour-long exposure of 60 adult asthmatic patients to pollution. Exposure took place at a street in London where the traffic was intense and predominantly diesel-based (Oxford Street). Patients were subsequently (3 weeks later) also exposed to a car-free environment, at a large park (Hyde Park). The whole period of study took place in winter, so that possible exposure to pollens was avoided.
This randomised, cross-over study showed that in spite of the absence of clinical signs, there was a significant reduction of VEMS and FVC (Forced Vital Capacity) after the walk along Oxford Street in comparison with that in Hyde Park. These effects were more evident in patients with moderate asthma than in patients with mild or intermittent Asthma.
The aforementioned effects were associated with a neutrophilic inflammation as detected in sputum, with increased acidification and increased levels of markers such as those of myeloperoxydase and IL-8.
Comparative measurements of different atmospheric pollutants (NO, NO2, CO2, PM10, PM2,5, Ultra-fine particles) showed a correlation between the respiratory and immunologic effects and the presence of Carbon (elementary) and ultra-fine particles (<0.01µm in diameter) that are largely predominant in diesel particles.
The interest of this study resides upon its direct and in real-time demonstration of the deleterious effects of the exposure of asthmatic patients to automobile pollution and, above all, to diesel particules, even in the absence of evident clinical signs indicating worsening of asthma.
Studies carried out in australian children have stressed that more than 80 % of the cases of moderate atopic eczema were associated with high levels of IgE-dependent sensitisation to food (Food Sensitisation = FS).
D. J. Hill et al (Confirmation of the association beteween high levels of IgE food sensitization and eczema in infancy. Clinical and Experimental allergy 2007 38 161-168) have attempted to confirm these observations in a vast international, multicentre study involving 92 centres in 12 countries. The study included 2048 patients (1246 male) with atopic eczema, from atopic families, (mean age of 17.6 months, age range between 11.8 and 25.4 months).
Data recorded included clinical history, an index of eczema severity based on SCORAD, measurements of total and cow’s milk-, egg- and peanut-specific IgE serum levels.
If values in relation to age surpassed 95 % of the predictive values of a food allergy, individuals were regarded as patients at high risk of IgE-mediated sensitisation.
Of the 2048 available serum samples, 55.5 % were from atopic patients.
The frequency of IgE-FS to cow’s milk, eggs and/or peanut was more important in patients whose eczema had developed before 3 months of age, as compared to those whose eczema had appeared at a later age, after 12 months of age (p < p 0.0001).
In order to avoid confounding factors, a logistic regression analysis was performed, which confirmed that children with IgE-FS had the most severe eczema and also eczema that had developed earlier (p < 0.001) : 64 % of severe eczemas involved IgE-FS children.
The profile of these children with eczema thus seems to include an early beginning of manifestations, a higher severity of the disease and a higher frequency of elevated levels of IgE-FS.
These results suggest that, according to the authors, a systematic search for food allergies in moderate to severe eczemas must be performed in children.
However, it should be stressed that the absence of serum IgE, on its own, does not allow one to exclude the possibility of true food allergies.
Novel French multicentre study of Sublingual Immunotherapy in Pollinosis
Started by various italian authors, and then international, sublingual immunotherapy has definitely acquired the right to be included in the anti-allergic therapeutic arsenal. (cf cefcap: Actualités 2002, 2003, 2004) In France, its efficacy was demonstrated convincingly in allergic rhinitis, either pollen- or house dust mite-induced, in adults and children, providing very important doses of allergens were used (Stallergènes®) and a long term treatment was performed.
What novel findings does the study by De Blay et coll., published in English, bring us ? (Ann.Allergy Asthma Immunol 20070990453-461) It is a randomised, multicentre study, involing 3 University Hospitals : Strasbourg, Nancy, Paris and 8 Hospital Centres of Allergy scattered throughout the french territory. It includes 118 patients between 12 and 41 years of age and treated using an association of 3 pollen allergen extracts (Dactylis, Phleum and Lolium; Allerbio® Laboratories) for 10 months. It aimed at confirming the efficacy and safety of the treatment as well as adherence of subjects to the treatment (compliance).
Its methodology is classical, with recording of the clinical symptoms, instrumental measurement of nasal obstruction, application of a quality of life questionnaire, immunological criteria, pollen counts collected according to different regions; all data analysed using a sophisticated statistical approach. It was found that with oral doses that are 350 times higher than those normally used for injection immunotherapy,
1) efficacy in seasonal pollen-induced rhinitis was confirmed,
2) providing they are not associated with Asthma;
3) safety is total, with the exception of some transitory oral pruritus
4) compliance is excellent (estimated to be 97%)
5) anti-Dactylis IgG 4 levels were increased at the end of treatment (2 to 3 times over their initial value).
The authors also stress the need for a standardisation of allergen extracts that can be used by the practicing physician.
