Primary cutaneous anaplastic large cell lymphoma shows a distinct miRNA expression profile and reveals differences from tumor-stage mycosis fungoides

Copyright @ 2012 John Wiley & SonsThe miRNA expression profiles of skin biopsies from 14 primary cutaneous anaplastic large cell lymphoma (C-ALCL) patients were analysed with miRNA microarrays using the same control group of 12 benign inflammatory dermatoses (BID) as previously used to study the miRNA expression profile of tumor-stage mycosis fungoides (MF). We identified 13 differentially expressed miRNAs between C-ALCL and BID. The up-regulation of miR-155, miR-27b, miR-30c and miR-29b in C-ALCL was validated by miRNA-Q-PCR on independent study groups. Additionally, the miRNA expression profiles of C-ALCL were compared with those of tumor-stage MF. Although miRNA microarray analysis did not identify statistically significant differentially expressed miRNAs, miRNA-Q-PCR demonstrated statistically significantly differential expression of miR-155, miR-27b, miR-93, miR-29b and miR-92a between tumor-stage MF and C-ALCL. This study, the first describing the miRNA expression profile of C-ALCL, reveals differences with tumor-stage MF, suggesting a different contribution to the pathogenesis of these lymphomas.This work was funded by grants from Netherlands Organization for Scientific Research (NWO) (MHV) and the Fondation Rene´ Touraine (MvK), and grants from the Leukaemia and Lymphoma Research (EB) and the Julian Starmer-Smith Memorial Fund (CHL)

Clusterin expression in cutaneous CD30-positive lymphoproliferative disorders and their histologic simulants

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73222/1/j.1600-0560.2008.01036.x.pd

The influence of autoantibody status and characteristics on the course of rheumatoid arthritis

The identification of ACPA has been a major breakthrough in the understanding of pathogenesis in RA. It has become clear that this unique autoantibody response identifies more homogenous subsets of patients with RA than those characterized by levels of other autoantibodies, and that differing disease courses possibly reflect the involvement of ACPA in disease pathogenesis. The elucidation of the characteristics of the ACPA response have shown that ACPA are not pathogenic per se, as illustrated by the fact that most patients are ACPA-positive a while before they develop disease. Possibly, a more mature ACPA response__as illustrated by more extensive isotype switching, enhanced antigen-recognition profile and higher titers__might be required for these autoantibodies to contribute to disease pathogenesis. Once RA is established, the ACPA response does not seem to mature. Nonetheless, ACPA status is important for clinical decision making, as it is the factor that is most predictive of disease outcome and associates with the effectiveness of various interventionsReumafonds, Abbvie BV, Pfizer BV, Roche BV, Chipsoft BVUBL - phd migration 201

Acute leukaemia in children : aspects of diagnosis and treatment

This thesis describes clinical, cytological, immunological and pharmacological aspects of acute childhood leukaemia and allogeneic stem cell transplantation(SCT), with the emphasis on the analysis of potential improvements in risk stratification and possible treatment adaptation, in order to decrease relapse frequency and disease-related death. Firstly, to study the role of chemokine receptor/ligand interactions in the context of extramedullary leukaemia, we analyzed the homing receptor expression on leukemic blast cells in skin or intestine, peripheral blood and bone marrow of patients with T-ALL en AML, respectively. Secondly, the treatment results of 132 children, who received an allogeneic HLA-identical SCT for acute leukaemia was evaluated, showing the effect of biologically effective TBI dose on relapse risk. Thirdly, to optimize the use of Cyclosporin A(CsA) for adequate Graft-versus-host disease(GVHD) prophylaxis and to avoid drug toxicity, we investigated the pharmacokinetics of CsA in children after SCT, and showed that monitoring CsA exposure early after SCT may provide a tool to influence outcome. Finally, to gain a better understanding of the mechanism of chimerism induction of endothelial and epithelial cells following allogeneic SCT, the occurrence of chimerism in relation to the conditioning regimen, time interval after SCT and development of GVHD was studied.Dutch Cancer SocietyUBL - phd migration 201

Tolerantie, zorg of zegen

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Samen sterk

Ter gelegenheid van zijn afscheid als hoogleraar in de Huid- en Geslachtsziekten aan de Universiteit Leiden op vrijdag 16 september 2016</p

Analysis of Major Histocompatibility Antigens and the Mononuclear Cell Infiltrate in Halo Nevi

A series of monoclonal antibodies was used to characterize the nevomelanocytes and the inflammatory infiltrate of 11 halo nevi in different stages of resolution, employing an immunoperoxidase technique. Three of the 11 halo nevi histologically showed signs of mild or moderate nevomelanocytic atypia. It was found that the vast majority of the nevomelanocytes in halo nevi with a dense inflammatory infiltrate markedly expressed HLA-A,B,C antigens, while expression was not demonstrable in nevocellular nests not adjacent to the mononuclear infiltrate. No difference in expression of HLA-A,B,C antigens was found between the 3 cases with mild or moderate nevomelanocytic atypia and the other eases lacking atypia. Expression of HLA-DR (Ia-like) antigens was found on few nevomelanocytes in only 2 of 11 lesions. The cellular composition of the mononuclear inflammatory infiltrate showed a predominance of T cells (80% or more) with a relatively high proportion of cytotoxic/suppressor T cells. Most of the T cells showed signs of activation as judged by staining for HLA-DR antigens. These results demonstrate that the expression of HLA- A,B,C antigens on the nevomelanocytes and the cellular composition of the mononuclear inflammatory infiltrate in halo nevi are very similar to that in malignant melanomas and dysplastic nevi. These findings also indicate that the expression of HLA-A,B,C antigens on nevomelanocytes is primarily dependent on the presence of T- cell immune response and not necessarily related to the presence of nevomelanocytic atypia