title: Flow cytometric analysis of intestinal intraepithelial lymphocytes in the diagnosis of refractory celiac sprue.
abstract: The etiology of refractory celiac sprue (RCS) is unclear. In a high proportion of cases, the clonal nature of intestinal intraepithelial lymphocytes (IEL) can be demonstrated and a pathogenetic implication of intestinal IEL has been postulated. The prognosis of this subgroup of RCS is poor, with a high risk to develop an overt lymphoma and uncontrolled malabsorption despite steroid/immunosuppressive therapy. Cases with a relatively indolent clinical course, however, exist and their early diagnosis may be difficult. To gain insight into the pathogenic implication of intestinal IEL in refractory celiac sprue, we have performed an extensive phenotypic and functional characterization of clonal intestinal IEL in a patient with an indolent form of refractory celiac sprue, using multiparametric flow cytometry. The abnormal lymphocyte infiltrate lacked surface membrane expression of CD3/T-cell receptor (TCR) complexes (TCR(-), CD4(-), CD8(-), sCD3(-)), but contained intracellular CD3(epsilon) (CyCD3(+)) and surface CD103(+) and CD7(+). In particular, these cells showed a unique spontaneous ex-vivo cytokine secretion profile with an increased percentage of CD3(-) IEL containing TNF-alpha and IL-10, in the absence of IL-2, IL-4 and IFN-gamma. Altogether our results suggest that flow cytometry immunophenotyping of intestinal IEL, in cases suspected of celiac disease and their complicated forms, could be of great help in the correct diagnosis of RCS and the understanding of the immunopathogenic mechanisms of the disease and their clinical and/or therapeutical implications.
authors.affiliation: Department of Immunology, Hospital Ramón y Cajal, Madrid, Spain. sanchezlaura99@yahoo.es
authors.forename: Laura B
authors.initials: LB
authors.lastname: Sanchez-Muñoz
authors.forename: Almudena
authors.initials: A
authors.lastname: Santón
authors.forename: Ana
authors.initials: A
authors.lastname: Cano
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez
authors.forename: Julia
authors.initials: J
authors.lastname: Almeida
authors.forename: Alberto
authors.initials: A
authors.lastname: Orfao
authors.forename: Luis
authors.initials: L
authors.lastname: Escribano
authors.forename: Garbiñe
authors.initials: G
authors.lastname: Roy
mesh_terms: D002446:Celiac Disease / Q000276:immunology*; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D005434:Flow Cytometry; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor; D006801:Humans; D016130:Immunophenotyping; D007413:Intestinal Mucosa / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D016207:Cytokines