Project description:Approximately 2–5% of adult-onset coeliac disease (CD) patients develops refractory coeliac disease (RCD). In contrast to RCD type I, RCD type II is characterised by the presence of aberrant small intestinal intraepithelial T-lymphocytes (IEL) expressing cytoplasmic CD3 but lacking surface expression of CD3, CD4 and CD8. Development of Enteropathy Associated T-cell Lymphoma (EATL) is directly associated with the presence of >20% aberrant IEL in RCD II patients and has a very poor prognosis. We report on an exceptional case of EATL presenting as leukemic ascites and on the unique opportunity to perform extensive phenotypic and genomic analysis of this malignancy. Flow cytometric immunophenotyping of the ascitic EATL presentation showed CD30 expression typical for EATL and loss of the above mentioned surface markers similar to the aberrant IEL it originated from, as indicated by an identical monoclonal TCR-gamma rearrangement. In addition, expression of a substantial number of markers, including CD2, CD7, CD11a/CD18, CD52, CD103 and granzyme B was lost, which has not been reported sofar. Expression of proliferation markers Ki-67 en PCNA was clearly detected in the majority of EATL cells. Karyotype and comparative genomic hybridisation (CGH) analyses showed many genomic alterations, including chromosomal gains and losses up to 47Mb not previously reported for EATL. In conclusion, the current exceptional EATL presentation displays both immunophenotypic and genomic alterations not described previously and not included in the current WHO classifications of lymphoid malignancies. Comparative genomic hybridisation (CGH) analyses of an exceptional case of enteropathy associated T cell lymphoma
Project description:Approximately 2–5% of adult-onset coeliac disease (CD) patients develops refractory coeliac disease (RCD). In contrast to RCD type I, RCD type II is characterised by the presence of aberrant small intestinal intraepithelial T-lymphocytes (IEL) expressing cytoplasmic CD3 but lacking surface expression of CD3, CD4 and CD8. Development of Enteropathy Associated T-cell Lymphoma (EATL) is directly associated with the presence of >20% aberrant IEL in RCD II patients and has a very poor prognosis. We report on an exceptional case of EATL presenting as leukemic ascites and on the unique opportunity to perform extensive phenotypic and genomic analysis of this malignancy. Flow cytometric immunophenotyping of the ascitic EATL presentation showed CD30 expression typical for EATL and loss of the above mentioned surface markers similar to the aberrant IEL it originated from, as indicated by an identical monoclonal TCR-gamma rearrangement. In addition, expression of a substantial number of markers, including CD2, CD7, CD11a/CD18, CD52, CD103 and granzyme B was lost, which has not been reported sofar. Expression of proliferation markers Ki-67 en PCNA was clearly detected in the majority of EATL cells. Karyotype and comparative genomic hybridisation (CGH) analyses showed many genomic alterations, including chromosomal gains and losses up to 47Mb not previously reported for EATL. In conclusion, the current exceptional EATL presentation displays both immunophenotypic and genomic alterations not described previously and not included in the current WHO classifications of lymphoid malignancies.
Project description:Analysis of ex vivo isolated lymphatic endothelial cells from the dermis of patients to define type 2 diabetes-induced changes. Results preveal aberrant dermal lymphangiogenesis and provide insight into its role in the pathogenesis of persistent skin inflammation in type 2 diabetes. The ex vivo dLEC transcriptome reveals a dramatic influence of the T2D environment on multiple molecular and cellular processes, mirroring the phenotypic changes seen in T2D affected skin. The positively and negatively correlated dLEC transcripts directly cohere to prolonged inflammatory periods and reduced infectious resistance of patients´ skin. Further, lymphatic vessels might be involved in tissue remodeling processes during T2D induced skin alterations associated with impaired wound healing and altered dermal architecture. Hence, dermal lymphatic vessels might be directly associated with T2D disease promotion.
Project description:Enteropathy associated T-cell lymphoma (EATL) is a rare non-Hodgkin lymphoma that may complicate celiac disease and typically occurs in patients with refractoriness to the gluten- free diet. The majority of these patients harbor intra-epithelial lymphocytes (IEL) with an aberrant phenotype in the small intestine which are thus considered as the ‘precursor’ lymphoma cells. We here report on a case of extra-intestinal EATL that originated from a clonal γδ-IEL population rather than from aberrant IEL. This EATL displayed a distinctive pattern of immunophenotypical, T-cell receptor immunogenetic, and chromosomal aberrancies defining this lymphoma as a novel variant of EATL.
Project description:Enteropathy associated T-cell lymphoma (EATL) is a rare non-Hodgkin lymphoma that may complicate celiac disease and typically occurs in patients with refractoriness to the gluten- free diet. The majority of these patients harbor intra-epithelial lymphocytes (IEL) with an aberrant phenotype in the small intestine which are thus considered as the M-bM-^@M-^XprecursorM-bM-^@M-^Y lymphoma cells. We here report on a case of extra-intestinal EATL that originated from a clonal M-NM-3M-NM-4-IEL population rather than from aberrant IEL. This EATL displayed a distinctive pattern of immunophenotypical, T-cell receptor immunogenetic, and chromosomal aberrancies defining this lymphoma as a novel variant of EATL. sample vs reference
Project description:Analysis of ex vivo isolated lymphatic endothelial cells from the dermis of patients to define type 2 diabetes-induced changes. Results preveal aberrant dermal lymphangiogenesis and provide insight into its role in the pathogenesis of persistent skin inflammation in type 2 diabetes. The ex vivo dLEC transcriptome reveals a dramatic influence of the T2D environment on multiple molecular and cellular processes, mirroring the phenotypic changes seen in T2D affected skin. The positively and negatively correlated dLEC transcripts directly cohere to prolonged inflammatory periods and reduced infectious resistance of patients´ skin. Further, lymphatic vessels might be involved in tissue remodeling processes during T2D induced skin alterations associated with impaired wound healing and altered dermal architecture. Hence, dermal lymphatic vessels might be directly associated with T2D disease promotion. Global gene expression profile of normal dermal lymphatic endothelial cells (ndLECs) compared to dermal lymphatic endothelial cells derived from type 2 diabetic patients (dLECs).Quadruplicate biological samples were analyzed from human lymphatic endothelial cells (4 x diabetic; 4 x non-diabetic). subsets: 1 disease state set (dLECs), 1 control set (ndLECs)