Antigen Absorption by the Jejunal Epithelium of Children with Cow's Milk Allergy

Abstract

ABSTRACT. To establish if intestinal permeability to exogenous antigens is involved in cow's milk allergy (CMA) in infants, 33 children 1 to 24 months old (18 controls and 1 5 with CMA) were tested for intestinal permeability to the protein marker horseradish peroxidase (HRP). Jejunal biopsies were performed either during the initial period of diagnosis, at the mean (and SE) age of 3 f 1 months, and/or 1 yr later, at the age of 13 f 2 months, just before and after a milk challenge. A small fragment of the biopsy was studied for histology and the remainder was mounted in an Ussing chamber for simultaneous measurement of mucosal to serosal transport of H R P in its intact and degraded forms and electrical parameters including short-circuit current and conductance. No modification in H R P absorption was noted in control children aged from 2 months to 11 yr, indicating that gut closure probably occurred earlier in life. During the initial period of CMA, transepithelial H R P fluxes were significantly higher, about 8-fold, in children with CMA (intact H R P flux = 48.5 f 15.2, 95% confidence interval, 11.2 to 85.7 versus 5.9 + 1.2, 95% confidence interval 2.9 to 8.3, in control children) In addition, short-circuit current was increased but conductance was unchanged. After several months on a milkfree diet, H R P flux and short-circuit current returned to control values. Just after the milk challenge and independently of -the clinical issue, a slight rise in H R P permeability was observed but it was not significant and remained within control values. These results suggest that increased permeability to proteins is probably not the primary cause of CMA, and that the increase in protein endocytosis noted during the initial period of CMA seems rather to be a secondary effect of an abnormal immunological response leading to mucosal inflammation and impairment of the endocytic process. (Pediatr Res 24:197-202, 1988)

Local Immune Response Measured in Blood Lymphocytes Reflects the Clinical Reactivity of Children with Cow's Milk Allergy

“…Second, the absorbed antigens must evoke harmful immunologic responses. Intestinal permeability has been shown to be increased in CMA patients with gastrointestinal symptoms either at the acute stage of the disease or after a milk challenge, but not on an elimination diet (3,4). These findings might reflect mucosal damage caused by local hypersensitivity mechanisms.…”

Early Dietary Antigens Delay the Development of Gut Mucosal Barrier in Preweaning Rats

“…In infants, it is not as yet known how long this period of increased neonatal permeability of the small intestine continues (2,3). However, this occurs at a period when the immune defense mechanisms are immature (4).…”

Glucagon-like peptide-2-enhanced barrier function reduces pathophysiology in a model of food allergy

“…Although some antigenic proteins are endocytosed into enterocytes and transported across the epithelium via the transcellular pathway, most proteins are degraded by intracellular enzymes, thus eliminating their antigenic properties (22). However, increased intestinal permeability has been documented in vivo in patients with food allergy (4,19), as well as in biopsy specimens (12) and in animal models of food hypersensitivity (3,10,17,21,24). It is clear that in sensitized individuals intact antigen does penetrate the epithelium to induce both immediate hypersensitivity and late-phase allergic reactions.…”