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Notes: Objective To evaluate the influence of perinatal environmental factors on early sensitization, atopic dermatitis and wheezing during the first year.Methods Information on pregnancy-related factors, parental atopic history, environmental factors and the clinical course of the infant until age one was gathered by questionnaires, as part of a prospective birth cohort study (Prospective study on the Influence of Perinatal factors on the Occurrence of asthma and allergies [PIPO-study]). Quantification of total and specific IgE was performed in 810 children and their parents.Results Early sensitization was found in 107/810 (13%) of the infants. Multiple regression analysis showed that specific IgE in fathers was a risk factor for early sensitization in their daughters (adjusted odds ratios (ORadj) 2.21 (95% confidence interval (CI) 1.10–4.49); P=0.03), whereas in boys, day care attendance was shown to be protective for early sensitization (ORadj 0.38 (95% CI 0.20–0.71); P=0.001). Atopic dermatitis occurred in 195/792 infants (25%). Specific IgE in the mother (ORadj 1.52 (95% CI 1.06–2.19); P=0.02) and in the infant (ORadj 4.20 (95% CI 2.63–6.68); P〈0.001) were both risk factors for the occurence of atopic dermatitis, whereas postnatal exposure to cats was negatively associated with atopic dermatitis (ORadj 0.68 (0.47–0.97); P=0.03).Postnatal exposure to cigarette smoke (ORadj 3.31 (95% CI 1.79–6.09); P〈0.001) and day care attendance (ORadj 1.96 (95% CI 1.18–3.23); P=0.009) were significantly associated with early wheezing, which occurred in 25% (197/795) of the infants.Conclusion The effect of paternal sensitization and day care attendance on sensitization is gender dependent. Maternal sensitization predisposes for atopic dermatitis, whereas postnatal exposure to cats had a protective effect.

Notes: Background Different types of circulating dendritic cells have been described. Dendritic cells influence differentiation of naive T lymphocytes into T helper type 1 (Th1) and Th2 effector cells.Objective The purpose of this study was to evaluate the number of circulating DC subtypes in peripheral blood of allergic and healthy children and in cord blood of neonates from allergic and non-allergic parents.Methods Circulating dendritic cells were flow cytometrically identified in whole blood samples as lineage (CD3, CD14, CD16, CD19, CD20, CD56) negative, CD34 negative and HLA-DR-positive cells. According to the expression of CD123 and CD11c, different DC subtypes were identified.Results Apart from DC1 (CD11c+ CD123dim+) and DC2 (CD11c– CD123high+), a third DC population was described with less differentiated phenotypic characteristics, namely CD11c– CD123dim+, and therefore defined here as less differentiated DC (ldDC). These ldDC represented the major DC population in cord blood and showed an age-depended decrease. The highest level of ldDC was detected in children with atopic dermatitis, whereas asthmatic children showed the lowest ldDC counts. Furthermore, high-dose inhaled corticosteroid treatment in asthmatic children was related to a decreased ldDC number. The number of circulating DC2 was significantly lower in allergic children, especially in asthmatics, compared to healthy children. In cord blood, no differences in DC subtypes were detectable between neonates at low and high risk for allergic disorders.Conclusion These results indicate that, apart from DC1 and DC2, a third population of dendritic cells, identified as CD11c– CD123dim+ cells and defined as less differentiated DC, must be considered in the evaluation of circulating DC. Furthermore, DC2 counts were decreased in allergic children, especially in asthmatics, which might be the consequence of an increased recruitment to the target organs.

Notes: During the last 5 years, an increasing number of studies have demonstrated that flow cytometric quantification of in vitro basophil activation can be a quite performant and reliable tool to measure IgE-dependent allergen-specific responses in allergic patients. So far, most assays have used CD63 as a basophil activation marker and native allergen extracts for stimulation. However, other basophil markers and recombinant allergens have recently been introduced. The technique has been applied for the diagnosis of allergy to pollen, house dust mite, food, natural rubber latex, hymenoptera venom and drugs. In addition, the technique has proven to be useful in non-IgE-mediated reactions such as hypersensitivity to drugs as well as detection of auto-antibodies in chronic urticaria. This review will focus on some specific issues: (1) principles of flow cytometric analysis of in vitro-activated basophils, (2) general technical aspects of the technique (including passive sensitization), (3) clinical applications and (4) recommendations for further development and evaluation of the technique.

Notes: Background During the last decade, evidence has been provided for profilins and cross-reactive carbohydrate determinants (CCDs) to be capable of inducing cross-reactive IgE antibodies with little clinical relevance.Objective To investigate the prevalence of sensitization to CCD and profilin in isolated allergies (birch, timothy grass, house dust mite, pets (cat and/or dog), natural rubber latex (NRL) and hymenoptera venom). To study the contribution of anti-CCD and anti-profilin IgE antibodies as a cause of clinically irrelevant IgE for NRL and apple.Methods For the first part of the study, 100 patients with inhalant allergy, 17 patients with NRL allergy and 40 patients with venom anaphylaxis were enrolled. Diagnosis was based on a questionnaire and a positive IgE determination and skin test for relevant allergen. Patients were identified as sensitized to CCD if they had a negative prick test and positive IgE for the glycoprotein bromelain. Sensitization to profilin was assessed by IgE for rBet v 2 (recombinant birch profilin). For the second part of the study, sera containing IgE against apple (n=82) or NRL (n=38) were classified as true-negative or false-positive according to the presence or absence of an oral allergy syndrome (OAS) or NRL-induced anaphylaxis. In these patients, sensitization to CCD and profilin was evaluated as described above.Results No sensitization to bromelain-type CCD and profilin was found in isolated birch pollen or NRL allergy. In contrast, sensitization to bromelain-type CCD was found in 4/17 patients with isolated grass pollinosis, 5/24 patients with combined pollinosis (birch, timothy, mugwort) and 7/33 patients with venom anaphylaxis. Sensitization to profilin was almost restricted to patients with combined pollen allergy (5/24). In pollen-allergic individuals with a false-positive IgE against NRL the prevalence of sensitization to bromelain-type CCD and profilin IgE was higher than in NRL-allergic patients (P〈0.00001 and P=0.0006, respectively). In pollen-allergic individuals with a false-positive IgE to apple, the frequency of sensitization to bromelain-type CCD was higher than in OAS patients (P=0.004). Clinically irrelevant NRL and apple were also found in four and five out of the seven patients sensitized to venom CCD, respectively. In pollinosis, clinically irrelevant NRL and apple IgE antibodies were inhibited by bromelain and recombinant birch profilin, whereas in isolated venom anaphylaxis these antibodies were inhibited by bromelain.Conclusions Patients monoallergic to NRL or birch pollen showed no sensitization to bromelain-type CCD or profilin. Sensitization to profilin and/or bromelain-type CCD, caused by pollen (timothy grass, mugwort) or hymenoptera venom allergens, can elicit false-positive IgE antibodies against NRL and apple.

Notes: Venom immunotherapy (VIT) has proven to be safe and effective in wasp venom anaphylaxis. However, there are no good parameters to indicate when to stop venom immunotherapy.〈section xml:id="abs1-2"〉〈title type="main"〉ObjectiveTo evaluate the relationship of the lymphocyte transformation test (LTT) to history and specific IgE determination, and to address the time course of lymphocyte transformation responses to wasp (Vespula) venom during VIT and the possible utility of LTT to determine the duration of therapy.〈section xml:id="abs1-3"〉〈title type="main"〉MethodsPeripheral blood mononuclear cells (PBMCs) of 18 individuals with a history of wasp sting anaphylaxis and a positive serum-venom-specific IgE, were stimulated with wasp venom before immunotherapy, at the end of a 5-day semi-rush immunotherapy and at 24 months during venom immunotherapy. Results, expressed as stimulation index (SI), were compared with the SI in seven asymptomatic stung controls.〈section xml:id="abs1-4"〉〈title type="main"〉ResultsIn controls the median (minimum–maximum) of the SI were 2.39 (0.52–3.39) before therapy and 2.39 (1.12–6.02) when repeated after 24 months. For patients the median (minimum–maximum) of the SI were 10.13 (1.19–44.88) before immunotherapy (d0), 2.73 (0.67–12.03) at the end of the build-up immunotherapy (d5) and 4.21 (0.88-14.66) at the end of 24 months of maintenance therapy (m24). The proliferation responses in vespid-allergic patients were significantly higher than in stung controls (P = 0.006) but only13/18 patients showed a positive LTT result before the start of immunotherapy (sensitivity of the LTT 72%). When the LTT was repeated after a 5 day build-up hyposensitization course the SI significantly dropped as compared to the pre-treatment levels (P = 0.002). The SI of the LTT was negative in eight out of 18 patients at 24 months and the median values were significantly lower than before therapy (P = 0.03).〈section xml:id="abs1-5"〉〈title type="main"〉ConclusionsAlthough, in the absence of sting challenge data it is not possible to draw conclusions about the predictive value of the LTT, our data may suggest that abolition of the LTT during VIT might indicate clinical insensitivity. Further studies, comparing the results of sting challenges, with the results of lymphocyte transformation will be necessary in order to evaluate the role of LTT in stopping immunotherapy.

Notes: Human seminal plasma anaphylaxis (HSPA) is rare but may be life-threatening. The antigen or antigens involved in these reactions reside in a glycoprotein fraction of human seminal plasma (HSP). We report a woman who experienced HSPA. Literature on the subject is reviewed.