Luisa Businco

A major susceptibility locus for atopic dermatitis maps to chromosome 3q21

Atopic dermatitis (eczema) is a chronic inflammatory skin disease with onset mainly in early childhood. It is commonly the initial clinical manifestation of allergic disease, often preceding the onset of respiratory allergies. Along with asthma and allergic rhinitis, atopic dermatitis is an important manifestation of atopy that is characterized by the formation of allergy antibodies (IgE) to environmental allergens. In the developed countries, the prevalence of atopic dermatitis is approximately 15%, with a steady increase over the past decades. Genetic and environmental factors interact to determine disease susceptibility and expression, and twin studies indicate that the genetic contribution is substantial. To identify susceptibility loci for atopic dermatitis, we ascertained 199 families with at least two affected siblings based on established diagnostic criteria. A genome-wide linkage study revealed highly significant evidence for linkage on chromosome 3q21 (Zall=4.31, P= 8.42×10−6). Moreover, this locus provided significant evidence for linkage of allergic sensitization under the assumption of paternal imprinting (hlod=3.71, α=44%), further supporting the presence of an atopy gene in this region. Our findings indicate that distinct genetic factors contribute to susceptibility to atopic dermatitis and that the study of this disease opens new avenues to dissect the genetics of atopy.

Allergenicity of goat’s milk in children with cow’s milk allergy

BACKGROUND Cows milk allergy (CMA) is a common disease of infancy and childhood. An appropriate cows milk (CM) substitute is necessary for feeding babies with CMA. CM substitutes are soy formulas and casein- or whey-based extensively hydrolyzed formulas. In several countries, including Italy, goats milk (GM) formulas are available, and some physicians recommend them for feeding babies with CMA. OBJECTIVE We sought to investigate, in vitro and in vivo, the allergenicity of GM in 26 children with proven IgE-mediated CMA. METHODS All the children underwent skin tests with CM and GM; detection of specific serum IgE to CM and GM; and double-blind, placebo-controlled, oral food challenges (DBPCOFCs) with fresh CM, GM, and, as placebo, a soy formula (Isomil, Abbott, Italy). CAP inhibition and immunoblotting inhibition assays were also carried out in 1 of 26 and 4 of 26 children with positive RAST results to both CM and GM, respectively. RESULTS All the children had positive skin test responses and CAP results to both CM and GM, all had positive DBPCOFC results to CM, and 24 of 26 had positive DBPCOFCs to GM. In CAP inhibition tests, preincubation of serum with CM or GM strongly inhibited IgE either to CM or to GM. In immunoblotting inhibition assays, preincubation with CM completely extinguished reactivity to GM, whereas GM partially inhibited reactivity to CM. CONCLUSIONS These data strongly indicate that GM is not an appropriate CM substitute for children with IgE-mediated CMA. A warning on the lack of safety of GM for children with CMA should be on the label of GM formulas to prevent severe allergic reactions in babies with CMA.

Allergenicity of milk protein hydrolysate formulae in children with cow's milk allergy

Cows milk protein hydrolysate formulae have been developed to lower or eliminate the allergenicity of cows milk proteins, and to reduce the antigenic load and the risk of sensitization. Cross-reactivity between different hydrolysate formulae and cows milk proteins has been demonstrated. We have studied 20 children (median age 31 months, range 15–76 months) with a history of IgE-mediated cows milk allergy. All the children had immediate allergic respiratory and/or cutaneous and/or gastro-intestinal reactions to cows milk ingestion. In addition, the children had positive prick skin tests and positive RAST to cows milk. Prick skin test, RAST, and double-blind placebo controlled food challenges were performed with three different hydrolysate formulae: a casein hydrolysate formula and two whey formulae, one partially and one extensively hydrolyzed. All 20 children had immediate allergic reactions after the challenge test with cows milk. Only 2/20 children had a positive challenge test with a casein hydrolysate formula (Alimentum): one developed asthma and one urticaria. Two of the 15 children challenged with an extensively hydrolysed whey formula (Profylac) developed perioral erythema. Nine out of 20 children had a positive challenge test with a partially hydrolysed whey formula (Nidina H.A.): four developed asthma, three urticaria and two lip oedema. All children had positive prick skin tests to cows milk proteins (casein and/or lactalbumin); 9 to Nidina H.A.; 3 to Profylac, and 3 to Alimentum. Specific IgE antibodies to cows milk were present in all children; in 13 to Nidina H.A., in 4 to Profylac, and in 3 to Alimentum.

Predictive value of cord blood IgE levels in ‘at‐risk’ newborn babies and influence of type of feeding

Cord serum IgE levels were examined in 101 newborn infants ofatopic parents, and reviewed at the ages of 3, 6, 9, 12, 15, 18, 21 and 24 months, in order to determine any relation with signs and symptoms of allergic rhinitis, bronchial asthma, atopic dermatitis, urticaria and food allergy.

Hypoallergenicity of an extensively hydrolyzed whey formula.

Several different protein hydrolysate‐based infant formulas have been promoted as hypoallergenic and considered suitable for the dietary management of cows milk allergy (CMA). Accepting that none of the hydrolysate‐based products is completely safe, the American Academy of Pediatrics (AAP) recommends that these formulas should be tested in a double‐blind placebo‐controlled setting and tolerated by at least 90% of children with proven CMA. In principle, this recommendation is also endorsed by the European Society of Paediatric Gastroenterology and Nutrition (ESPGAN) and the European Society of Paediatric Allergy and Clinical Immunology (ESPACI). In this two‐center study, 32 children with proven CMA were tested with the extensive hydrolysate whey formula Nutrilon Pepti, for comparison with Profylac (extensive) and Nan HA (partial) whey hydrolysate products. Skin‐prick tests (SPTs) were, respectively, positive to the three hydrolysate formulas in 19%, 15%, and 32% of children. After oral challenge it was concluded that 97% (95% CI: 85–100%) of the children tolerated Nutrilon Pepti, 94% (95% CI: 75–100%) tolerated Profylac, and 64% (95% CI: 37–81%) tolerated Nan HA. This study demonstrates that the extensive hydrolysates Nutrilon Pepti and Profylac are well tolerated in a population of children with proven CMA and that both products can be considered safe for their intended use. This study confirms that a very small number of children react even to extensively hydrolyzed formulas. SPT prior to oral exposure to the hydrolysate‐based formulas can indicate whether a child is at risk of showing reactions to the product. Introduction of new products to these children should be carried out under a doctors supervision. However, the majority of the SPT‐positive children did tolerate the two extensively hydrolyzed whey‐based formulas tested.

Allergenicity and nutritional adequacy of soy protein formulas

Soy protein formulas are used for different conditions, including cow milk protein allergy, lactose and galactose intolerance, and severe gastroenteritis. Feeding soy protein formulas to normal term infants is associated with normal growth, normal protein nutritional status, and normal bone mineralization. Recent studies of infants fed soy protein formulas exclusively during the first months of life revealed no immunologic abnormality; however, the use of such formulas for management of cow milk protein allergy and for prevention of atopy is controversial. Although in the past decade many studies have stressed soy allergenicity, soy allergenicity has been confirmed by the challenge test in only a few studies. In this article we review the studies dealing with the allergenicity of soy protein formulas. We also present our own data on their use in the prevention and management of cow milk protein allergy.

Breast milk from mothers of children with newly developed atopic eczema has low levels of long chain polyunsaturated fatty acids

BACKGROUND Infants at risk of atopic dermatitis have lower than normal levels of long chain polyunsaturated fatty acids. These fatty acids are normally present in substantial quantities in human breast milk. METHODS Because of the equivocal evidence concerning the ability of breastfeeding to delay the onset or reduce the severity of atopic dermatitis, we have analyzed the fatty acid composition of breast milk from the mothers of children with newly developed disease with the use of gas chromatography. RESULTS Breast milk lipids from mothers of children with newly developed atopic dermatitis had increased proportions of linoleic acid and significantly decreased proportions of its long chain polyunsaturated derivatives compared with a control group. The ratio of linoleic acid to the sum of its metabolites, gamma-linolenic acid, dihomo-gamma-linolenic acid, and arachidonic acid was 11.78 in the atopic group and 9.02 in the control group (p < 0.01). CONCLUSIONS These results are consistent with previous findings of an abnormal fatty acid status in atopic subjects and may account for some of the inconsistent results from studies of the effect of breastfeeding on the subsequent development of atopic dermatitis. We conclude that further studies to examine the effects of supplementation of the diet of breastfeeding mothers with long chain polyunsaturates should be done.

Primary immunodeficiency syndromes in Italy: A report of the national register in children and adults

The Italian Register for Immune Deficiencies was organized in 1977. Seven hundred ninety-seven cases of primary immunodeficiencies, diagnosed according to the World Health Organization criteria, have been registered up to April 1982. In this paper we report the percentages of the different forms of primary immunodeficiencies and the incidence of neoplastic and autoimmune diseases. A prevalence of humoral defects and selective IgA deficiency was found, followed by T-cell disorders. Two and thirty-eight hundredths percent of the patients developed cancer, and 5.89% developed autoimmune diseases. A comparison among the Italian, Swedish, and Japanese Registers showed a higher incidence of IgA defects in the Italian Register while nonspecific phagocyte defects were more frequent in the Swedish Register. The incidence of cancer and autoimmune disorders is similar to that observed in other registers.

Month of birth and grass pollen or mite sensitization in children with respiratory allergy: a significant relationship

This report describes a retrospective analysis of the month of birth distribution of 2124 children with respiratory allergy in the Rome district between 1964 and 1985, in comparison with the total live births in the same district over the same period. Of the 2124 children, 1685 had positive skin tests and or RAST only to mites, and 439 only to grass pollen (P < < 0.001). A significant relationship was found between grass or mite sensitization and the month of birth. A high proportion of children born in June‐September had mite allergy (P <0.005), and even higher was that of those born in March‐May with grass sensitivity (P< < 0.005), compared with the total live birth distribution in the Rome district in the same years as the children examined. These results are consistent with the idea that allergy may be associated with a period of susceptibility to sensitization in early infancy.

Heterogeneity of immunological abnormalities in ataxia-telangiectasia

Peripheral blood mononuclear cells from five patients with ataxia-telangiectasia were evaluated for their reactivity with a panel of monoclonal antibodies directed against T-cell subsets and for theirin vitro functions in a pokeweed mitogen-induced immunoglobulin biosynthesis assay. All the patients had significantly reduced proportions of cells identified by monoclonal antibodies to subpopulations of T lymphocytes with helper activity (OKT4 and 5/9) and produced low amounts or no IgA and IgGin vitro. Immunoglobulin biosynthesis was increased by the addition of normal x-irradiated peripheral blood mononuclear cells in one of three patients, suggesting a helper T-cell deficiency in this patient and intrinsic B-cell defects in the other two. Two patients had increased proportions of cells identified by a monoclonal antibody to a subpopulation of T lymphocytes which includes suppressor T cells (OKT8), and their cells were able to suppress immunoglobulin biosynthesis by peripheral blood mononuclear cells from normal donors. These findings indicate heterogeneous disturbances of immunoregulatory mechanisms in ataxia-telangiectasia.