J.A. Warner

Is deficiency of interferon gamma production by allergen triggered cord blood cells a predictor of atopic eczema

Abstract. Peripheral blood mononuclear cell proliferative responses and interferon‐γ product ion to anti‐CD3, cat fur extract, betalactoglobulin and ovalbumin were determined al birth in a group of 34 babies born to families where at least one parent was; atopic. The development of atopic eczema with positive allergy skin‐prick tests to cows’ milk and egg at 1 year of age, where the symptoms improved on an egg and milk‐free diet, was significantly associated with raised proliferative responses and defective IFN‐γ production to stimulation with betalactoglobulin with a trend for similar responses to ovalbumin. This was not observed in those who did not develop atopic eczema or those with atopic eczema not associated with foods. Responses to cat fur extract were not significantly different between those with and without atopic eczema. This has important implications for the prediction at birth, not only of the probability of being allergic, but also of the specific allergens which will cause problems. The implementation of specific targeted allergen avoidance during the critical period in infancy, therefore, should be more easily applied and should facilitate attempts to prevent disease.

Fetal peripheral blood mononuclear cell proliferative responses to mitogenic and allergenic stimuli during gestation

Blood samples were obtained from fetuses and premature babies (n=51) (15‐34 weeks gestation) to determine at what stage the fetal immune system was able to produce a positive proliferative response to common allergens. Peripheral blood mononuclear cells (PB MC) were stimulated with the mitogen, phytohaemagglutinin (PHA), and the allergens, house dust mite, cat fur. birch tree pollen, β‐lactoglobulin, ovalbumin and bee venom (mellitin). Results were expressed as ratios of stimulated to unstimulated 3H thymidine incorporation, and as percent positive responders. There was an increase in proliferation ratio which correlated with increasing gestational age for PHA (p < 0.0001), cat fur (p=0.042), birch pollen (p=0.022) and β‐lactoglobulin (p=0, 006). The point in gestation when cells from some individuals began responding to the allergens with a ratio of 2. 0 was at approximately 22 weeks. PBMC proliferative response ratios were higher from samples from babies > 22 weeks gestation compared to < 22 weeks for the mitogen and all allergens, except mellitin. There was also a greater proportion of positive responders from samples > 22 weeks compared to < 22 weeks for the mitogen and all allergens, except mellitin. Maternal exposure to birch pollen, which has a discrete season, was assessed to determine whether exposure had occurred at 22 weeks gestation or beyond. Results showed a higher prolifera tive response in infant cells stimulated with birch pollen (p=0.005) and higher proportion of positive responders (p=0.01) in the group of babies whose mothers had been exposed to hirch pollen beyond 22 weeks, compared to those whose mothers had not been so exposed. These results suggest that in utero fetal exposure to an allergen from around 22 weeks gestation may result in primary sensitisation to that allergen, leading to positive proliferative responses, at birth.

Detection of house-dust-mite allergen in amniotic fluid and umbilical-cord blood

Mononuclear cells in umbilical-cord blood display allergen-specific reactivity, but how allergen exposure occurs in utero is unknown. We investigated the presence of a common inhalant allergen (Der p 1), to which mothers are exposed throughout pregnancy, by ELISA in matched maternal blood and amniotic fluid samples at 16-17 weeks of gestation, and in matched maternal and umbilical-cord blood at term (> or =37 weeks of gestation). Der p 1 was detectable in 24 of 43 amniotic fluid samples where it was also present in maternal blood, and in 15 of 24 cord-plasma samples at significantly higher concentrations than in the maternal plasma (p=0.022). The detection of Der p 1 in the amniotic fluid and the fetal circulation provides direct evidence of transamniotic and transplacental allergen exposure.

Peripheral blood mononuclear cell proliferative responses in the first year of life in babies born to allergic parents

Background Raised peripheral blood mononuclear cells (PBMCs) proliferative responses to food allergens have been demonstrated in children with established atopic dermatitis.

Prenatal origins of allergic disease

The prevalence of asthma and related allergic disorders has increased considerably over the last 25 years. Because genetic stock has not changed, environmental factors must have influenced the phenotype. Infants who experience the development of allergy already have an altered immune response at birth. We have investigated the development of immune responses during gestation and the effect of maternal allergen exposure during pregnancy and infant exposure in the first month of life on the development of allergy and disease. There was higher specific peripheral blood mononuclear cell proliferation to house dust mite and birch pollen in the third trimester compared with the second trimester, with the first positive responses seen at 22 weeks gestation. Maternal exposure to birch pollen after 22 weeks resulted in higher infant peripheral blood mononuclear cell responses to birch pollen at birth. Infants born at term, with at least 1 atopic parent with asthma, who experienced the development of allergic symptoms and positive skin prick test by 1 year of age had raised proliferative responses to house dust mite at birth compared with those infants with no symptoms. In genetically predisposed individuals, antenatal factors including maternal and thereby fetal exposure to allergens and materno-placental-fetal immunologic interactions are active in determining whether an allergic predisposition is manifested as disease.

The effect of high‐efficiency and standard vacuum‐cleaners on mite, cat and dog allergen levels and clinical progress

The major triggers for allergic asthma are exposure to allergens of the house dust mite, Dermatophagoides pteronyssinus, and of pets. Unfortunately studies of techniques designed to reduce house dust mite and pet allergens have had mixed results. However, new so‐called ‘improved’ products continue to appear on the market and require subjective evaluation. The homes of 60 house dust mite‐allergic patients were studied to compare the effects of high‐efficiency and standard vacuum‐cleaners on allergen concentration. Der p 1 (house dust mite), Fel d 1 (cat) and Can f 1 (dog) allergens were measured in four separate locations in each home. Clinical analysis was by lung function, bronchodilator usage and histamine challenge techniques. There was a significant reduction in Fel d 1 (ng/m2) in dust samples from the living‐room carpet (p = 0.046), bedroom carpet (p = 0.003) and mattress (p = 0.013) and living‐room sofa (p = 0.005) after 12 months of using the high‐efficiency cleaners, but only in the mattress sample using the standard cleaners (p = 0.014). Can f 1 (ng/g dust) was reduced in the mattress sample after using the high‐efficiency vacuum‐cleaners (p = 0.028), but not at other sites. Der p 1 levels were not significantly changed over this period. Clinically, patients in the high‐efficiency group showed improvements in peak expiratory flow rate (PEFR) (p = 0.004), FEV1 (p = 0.026) and bronchodilator usage (p = 0.005) after 12 months. When the cat‐sensitive patients were analyzed separately, improvements in histamine PC20 (p = 0.039) were also seen. Reducing Fel d 1 concentrations, in the absence of any change in Der p 1 concentrations, can produce significant improvements in the lung function of atopic, asthmatic patients. This effect was primarily achieved in those patients with cat sensitivity, but who did not possess a cat themselves.

Maternofetal interaction and allergy

The hereditability of allergic disease was first described by Cooke & Vander Veer in 1916 ( 1 ). Analysis of their allergic patients demonstrated a familial tendency with atopy in 50% of children with one allergic parent and in 80% of those with two allergic parents. More recently, Ruiz et al. ( 2 ) showed that significantly more infants with an allergic mother developed allergic eczema than those with an allergic father. In 1992, Cookson et al. ( 3 ) reported that the transmission of atopy at the chromosome 1 lq locus was detectable only through the maternal line. These studies suggest that an atopic mother can modify the development of the infant immune response toward the allergic phenotype. It is possible that this could be brought about by the antibody and cytokine profiles experienced by the fetus irz utero. The placenta is embryonic in origin, and contains genetic material from both the mother and the father. It has the potential to express paternally derived antigens and, therefore, to be treated as foreign tissue by the mother. This was first described in 1954 by Medawar (4), who suggested that mechanisms to prevent rejection of the placenta by the maternal immune system must exist for pregnancy to be successful. One of these mechanisms involves placental troplioblasts in that they express a unique, slightly modified MHC class I antigen which does not trigger the maternal nonself rejection mechanisms ( 5 ) . However, fetal cells can pass into the maternal circulation, thereby enabling priming to occur in other locations in the mothers immune system. Maternal immune suppression at the placenE. A. Miles, B. M. Colwell, J. 0. Warner

Ovalbumin-specific immunoglobulin G and subclass responses through the first 5 years of life in relation to duration of egg sensitization and the development of asthma

Background Egg sensitization, particularly persistent sensitization, is a risk factor for later asthma. However, little is known about accompanying IgG and subclass responses and how they might relate to asthmatic outcome.

Cell matrix interactions in asthma

Chronic inflammatory responses, such as asthma, are chciracterized by extensive tissue remodelling resulting from the constant insults by inflammatory mediators and cytokines. Even in patients with mild asthma, there is evidence of inflammation and tissue remodelling [1]. These changes include damage to the epithelial layer [2], alterations in the proflle of matrix proteins [2,3], proliferation of myofibroblasts [2], influx of leucocytes [4,5] and changes in mast cell distribution [6,7]. While the pro-inflammatory effects of mediators or cytokines on the cells involved in asthma have been extensively investigated, the changes in the extracellular matrix may also affect these cells and have a profound effect on the course of the disease. While the importance of providing a suitable matrix for the growth of cell lines or tissue explants has been appreciated for many years, recent investigations have highlighted the profound effects that the matrix can have on cell signalling and gene expression [8-10]. Matrix proteins participate in attachment of cells, tissue growth and repair [It], proliferation and differentiation [12], cell migration and activation [13,14], cell survival/delay of apoptosis [15,16] and chemotaxis [17]. These interactions between the cell and matrix are transduced by adhesion molecules, including the integrins, on the surface ofthe cell. In addition to regulating adhesion to the endothelium and recruitment to the tissues [18], the integrins convey information about the cellular environment into the cell interior and influence a range of cellular responses [19,20]. Integrin-dependent signals are known to influence a range of responses including gene expression, cytokine production [8-10], cytoskeletal reorganization [21,22], eytoplasmic alkalinization [23] and protein phosphorylation [24-26]. The ability of the matrix to convey information into the cell via the integrins can occur in many different ways. The matrix composition may vary in different areas or there may be changes in the matrix isoforms expressed in disease [27]. Alternatively, there may be changes in the availability of ligand binding sites in different contexts [28] or the affinity of integrins for the matrix protein may be changed [29].