Immunohistochemical study of the apoptotic mechanisms in the intestinal mucosa during children's coeliac disease.

Mechanisms leading to morphological changes of the small intestine during coeliac disease (CD) are not yet completely recognized; however, two main processes have been suggested recently: remodeling of mucosa by matrix metalloproteinases, and mucosal atrophy by apoptosis. The aim of this study was analysis of the expression of proteins regulating apoptosis in the small intestine of children with active CD (ACD) and potential CD (PCD). Jejunal biopsies of 43 children with PCD and untreated ACD and 21 control samples were analyzed by means of standard indirect immunohistochemical technique for Fas, Fas ligand (Fas-L), tissue transglutaminase (tTG), Bcl-2, and glutathione S-transferase (GST) expression. We found significantly lower numbers of Fas-expressing enterocytes in the ACD patients than in PCD patients and controls. Similarly, the number of Fas-positive mucosal lymphocytes was decreased in ACD when compared with PCD. The number of Fas-L- and tTG-expressing enterocytes and mucosal lymphocytes was higher in both PCD and ACD. On the other hand, the number of Bcl-2-positive mucosal lymphocytes in PCD as well as ACD was significantly lower. The expression of tTG in extracellular matrix was significantly higher in PCD and ACD when compared with controls. Our results showed that Fas and/or Fas-L, Bcl-2, and tTG may be involved in apoptotic pathways leading to mucosal atrophy in children with CD. tTG changes are in agreement with the presumed role of this protein in the pathogenesis of CD.

BLIMP1α, the master regulator of plasma cell differentiation is a tumor supressor gene in B cell lymphomas.

AIMS: The aim of this review was to summarize recent knowledge of the structure and function of a transcriptional repressor, B lymphocyte induced maturation protein 1 (BLIMP1) and its participation in the pathogenesis of B lymphomas. METHODS AND RESULTS: This review summarizes the structure and function of BLIMP1, its major target genes and its role as a tumour suppressor in B cell lymphomas. We review our recent data implicating the loss of BLIMP1α as an important step in the pathogenesis of the Epstein-Barr virus (EBV) associated B cell lymphomas. CONCLUSIONS: BLIMP1 is a transcriptional repressor essential for the differentiation of germinal centre (GC) B cells to plasma cells. The loss of BLIMP1 in GC B cells could contribute to the pathogenesis of EBV-associated lymphomas by preventing plasma cell differentiation and viral replication.