title: Serum granzymes and CD30 are increased in children's milk protein sensitive enteropathy and celiac disease.
abstract: BACKGROUND
  Cow's milk protein sensitive enteropathy (CMSE) and celiac disease (CD) associate with upregulation of local intestinal immune responses, including activation of cytotoxic lymphocytes.
  
  
  OBJECTIVE
  We investigated whether this upregulation can be detected at the systemic level by analyzing serum concentrations of granzymes A (GrA) and B (GrB), soluble Fas, and CD30.
  
  
  METHODS
  Fifty-seven children with a final diagnosis of CMSE in 23 subjects (18 untreated and 5 on a diet), 20 untreated CD patients, and 14 control subjects with no gastrointestinal disease were examined by endoscopy for gastrointestinal complaints. Duodenal biopsies were studied for basic histology, CD3, alphabeta and gammadelta T-cell receptors (TCRs), and serum samples by commercial ELISA assays.
  
  
  RESULTS
  Concentrations of GrA and GrB were significantly higher in untreated CMSE and in CD as compared with the control subjects. Measurable GrB was present in only 20% of the control subjects but in 100% of patients with CMSE. CD30 was similarly increased in both untreated CMSE and CD cases, whereas in treated CMSE cases the concentrations were equal to the control subjects. All groups showed similar soluble Fas. The numbers of duodenal CD3 + , alphabeta- and gammadelta-TCRs correlated with the serum granzyme and CD30 levels.
  
  
  CONCLUSIONS
  The intestinal immune response in CMSE and CD is manifested by the increase in serum GrA, GrB, and CD30; the measurement of these markers provides a new practical and objective complementary means for diagnosis and assessment of treatment response. However, this has to be confirmed by more studies before routine use.
authors.affiliation: Department of Pathology, Oulu University, Finland.
authors.forename: Merja T
authors.initials: MT
authors.lastname: Augustin
authors.forename: Jorma
authors.initials: J
authors.lastname: Kokkonen
authors.forename: Riitta
authors.initials: R
authors.lastname: Karttunen
authors.forename: Tuomo J
authors.initials: TJ
authors.lastname: Karttunen
mesh_terms: D000293:Adolescent; D017252:CD3 Complex / Q000032:analysis; D002446:Celiac Disease / Q000097:blood / Q000209:etiology* / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004386:Duodenum / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D053804:Granzymes; D006801:Humans; D007413:Intestinal Mucosa / Q000276:immunology; D017730:Ki-1 Antigen / Q000097:blood*; D018655:Lymphocyte Count; D008297:Male; D016269:Milk Hypersensitivity / Q000097:blood / Q000209:etiology* / Q000276:immunology; D008894:Milk Proteins / Q000009:adverse effects*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis; D012697:Serine Endopeptidases / Q000097:blood*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: D017252:CD3 Complex; D017730:Ki-1 Antigen; D008894:Milk Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human