title: Abnormalities of Th1 function in non-IgE food allergy, celiac disease, and ileal lymphonodular hyperplasia: a new relationship?
abstract: BACKGROUND
  Non-IgE mechanisms may also be involved food allergy (FA). Our group has been studying the immunopathogenesis clinical entities in children with gastro-intestinal symptoms and in whom biopsies of the terminal ileum show lymphoid tissue masses referred to as ileal lymphonodular hyperplasia. Our more recent studies have demonstrated Th1/Th2 cytokine profiles associated with non-IgE FA and other clinical entities.
  
  
  OBJECTIVE
  We investigated 12 subjects with non-IgE FA (group 1) and 4 subjects with celiac disease (group 2). Cytokine profiles and immunologic studies of lymphocytes in peripheral blood and from gastro-intestinal biopsy tissues from patients in groups 1 and 2 were also evaluated.
  
  
  METHODS
  Group 1 consisted of 12 children with clinical symptoms of anorexia, diarrhea, and abdominal pain. The diagnosis of non-IgE FA was established by positive double-blind, placebo-controlled food challenge and reduced or negative immediate-type skin testing and negative IgE radioallergosorbent tests. Group 2 consisted of four patients with celiac disease and three adult females with biopsy-proven clinical symptoms of celiac disease.
  
  
  RESULTS
  In group 1, peripheral blood CD4 and CD8 lymphocyte distributions were normal, with a predominance of CD4+ cells with a decreased intracellular Th1 cytokine pattern and a normal Th2 intracellular cytokine pattern. In contrast, all four patients in group 2 not only displayed abnormal CD4 and CD8 peripheral blood lymphocyte distributions (CD8 > CD4), but also an abnormal predominance of CD4+ cells with an increased Th1 and a normal Th2 cytokine pattern. A similar abnormal pattern of CD4 > CD8 ratio was observed in intestinal biopsies. All 12 patients in group 1 showed lymphonodular hyperplasia in each of the biopsies and by ileoscopy.
  
  
  CONCLUSIONS
  These studies suggest that abnormalities in Th1 function may not only play a role in some patients with non--IgE-mediated FA in whom decreased Th1 function is seen, but also in patients with celiac disease in whom an increased Th1 function is seen. The studies also suggest that lymphonodular hyperplasia may be a hallmark histologic lesion in patients with non--IgE-mediated FA.
authors.affiliation: Department of Pediatrics and the International Center for Interdisciplinary Studies of Immunology, Georgetown University Medical Center, Washington, DC 20007, USA. bellantj@georgetown.edu
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Bellanti
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Zeligs
authors.forename: Jonathan
authors.initials: J
authors.lastname: Malka-Rais
authors.forename: Aderbal
authors.initials: A
authors.lastname: Sabra
mesh_terms: D001706:Biopsy; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D002446:Celiac Disease / Q000378:metabolism / Q000503:physiopathology*; D002648:Child; D002669:Child Welfare; D002675:Child, Preschool; D018849:Controlled Clinical Trials as Topic; D016207:Cytokines / Q000378:metabolism; D004219:District of Columbia; D004311:Double-Blind Method; D004804:Eosinophils / Q000378:metabolism; D005260:Female; D005512:Food Hypersensitivity / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000378:metabolism / Q000503:physiopathology*; D007082:Ileum; D007154:Immune System Diseases / Q000473:pathology*; D007073:Immunoglobulin E / Q000097:blood; D007150:Immunohistochemistry; D007223:Infant; D007420:Intestine, Large / Q000378:metabolism / Q000473:pathology; D007958:Leukocyte Count; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008297:Male; D011852:Radioallergosorbent Test; D012882:Skin Tests; D013223:Statistics as Topic; D018417:Th1 Cells / Q000378:metabolism / Q000502:physiology*; D018418:Th2 Cells / Q000378:metabolism / Q000473:pathology; D013952:Thymus Hyperplasia / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D016207:Cytokines; D007073:Immunoglobulin E