Clinical reactivity to beef in children allergic to cow's milk.

BACKGROUND: Cow's milk is one of the most common food allergens in children. Limited information is available on the prevalence of reactivity to a related food source, beef. The purposes of this study were to examine the prevalence of symptomatic sensitivity to beef in a selected pediatric population and to determine the frequency of concomitant reactivity to cow's milk and beef. METHODS: Children referred for assessment of atopic dermatitis and possible food hypersensitivity were evaluated for symptomatic reactivity to beef by double-blind placebo-controlled food challenges (DBPCFCs) and subsequent open feedings of beef. Sodium dodecyl-sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), immunoblot, and immunodot blot analyses were performed with patients' sera on preparations of beef extracts subjected to different cooking conditions: raw (no heating), medium, and well-cooked. RESULTS: Eleven of 335 children referred for evaluation of atopic dermatitis and possible food hypersensitivity were found to have symptomatic sensitivity to beef; eight were also sensitive to milk, as demonstrated in previous DBPCFCs. Eight patients reacted to beef during DBPCFC, and three tolerated beef in a DBPCFC and well-cooked beef in an open challenge but reacted to ingestion of less well-cooked beef. SDS-PAGE of raw beef revealed at least 24 protein fractions. Several protein bands in raw beef appeared to denature with heating. Bovine serum albumin and bovine gamma globulin were heat-labile in the beef extract, but six protein fractions persisted even after heating the beef extract for 2 hours at 85 degrees C. IgE from patients reacting to rare and well-cooked beef bound up to six of these heat-resistant fractions, but IgE from patients reacting only to rare beef failed to bind any of these fractions with one exception. In addition, patients reacting to rare and well-cooked beef had specific IgE to a 17.8 kd fraction, which was only weakly recognized by one patient reacting only to rare beef. CONCLUSIONS: Specific IgE antibodies to heat-labile beef proteins might explain why some patients can tolerate well-cooked beef but not medium-rare and rare beef. Patients reacting only to rare beef may not need to maintain a complete beef elimination diet.

Functional regulation of beta 1 integrins on human eosinophils by divalent cations and cytokines.

Divalent cations and various soluble stimuli can alter cell adherence by affecting the avidity of adhesion molecules. We hypothesized that beta 1 integrin function of human eosinophils may be altered by divalent cations and eosinophil-activating cytokines such as interleukin-5 (IL-5). Expression of the beta 1 integrin activation epitope recognized by monoclonal antibody (mAb) 15/7 was evaluated by flow cytometry using purified eosinophils from allergic subjects, normal subjects, and late-phase bronchoalveolar lavage (BAL) fluids. Rapid and reversible 15/7 binding on eosinophils from each source was induced in Mn2+ (0.01-1 mM) but not in buffers containing other divalent cations and occurred without affecting the total level of beta 1 integrin expression (quantified using mAb 33B6). Augmentation of eosinophil adhesion to immobilized vascular cell adhesion molecule (VCAM-1) in Mn2+ followed a similar concentration dependence as mAb 15/7 binding. Net binding to VCAM-1 in Mn2+ was completely inhibited with a mixture of alpha 4 and beta 1 integrin mAb while beta 2 integrin mAb had no effect. Exposure of eosinophils from allergic subjects to as little as 1 pg/ml IL-5 completely inhibited mAb 15/7 binding induced by Mn2+. In contrast, increased binding of mAb 15/7 in Mn2+ was not blocked by IL-5 in eosinophils from normal subjects. For eosinophils from allergic subjects, IL-5 also inhibited Mn(2+)-induced adhesion to VCAM-1. Thus, beta 1 integrins on eosinophils from allergic and nonallergic subjects are modulated differently by Mn2+ and IL-5. Altered beta 1 integrin avidity may be one mechanism involved in preferential eosinophil recruitment in vivo.