Immunologic tolerance mechanisms of early and late type food protein induced proctocolitis

Background: Food protein-induced colitis (FPIC), a disorder primarily affectingsmall infants has recently been described in older children, as well. It is mostly anon-IgE mediated disease where a T-cell-mediated reaction to cow?s milk protein, asa result of a defect in immunologic tolerance has been suggested. ? e mechanismscausing defective mucosal tolerance, however, has not been studied, so far.Aim: We determined the expression of TGF-ß, TGF-ß-receptor-1, TNF-?, CD86and CD23 on the colon mucosa to investigate their roles in the pathogenesis of thetwo subtypes of FPIC; infantile FPIC and FPIC of older children.Methods: We studied 57 patients with a mean age at referral of 2.9± 4.02 years.Group-I: infantile FPIC, <6 months, N=21; Group-II: FPIC of older children,>1.5 years of age, N=7; Group-III: non-allergic eosinophilic colitis, N=7; Group-IV: children with juvenile hyperplastic polyps, N=22. Immunohistochemical stainson colonic biopsy specimens were performed.Results: Group-II patients had significantly lower TGF-ß expression compared toother three groups. ? e expression of TNF-? was significantly higher in Groups-I,II and III compared to that of Group-IV. ? e expression of TGF-ß-receptor-1 wassignificantly lower (p=0.049) and CD86 higher in Group-I than in Group-IV(p=0.012). Eosinophil counts/HPF in lamina propria was significantly correlatedwith CD86 expression (p=0.026, r=0.388).Conclusion: Our results suggest that TNF-? is implictaed in the pathogenesis of allsubtypes of eosinophilic colitis of infancy and childhood, whether allergic in natureor not. ? e decreased activity of TGF-ß-receptor-1 accompanied by increasedexpression of CD86 in infants and decreased activity of TGF-ß in older childrenappear to play role in the development of FPIC.