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B-Zell-Pathomechanismen der akuten und chronischen Myositis: Ex-Vivo- und In-Vitro-Untersuchungen

dc.contributor.advisorSchmidt, Jens PD Dr.
dc.contributor.authorHoffmann, Luisa
dc.date.accessioned2014-04-22T12:12:59Z
dc.date.available2014-05-13T22:50:04Z
dc.date.issued2014-04-22
dc.identifier.urihttp://hdl.handle.net/11858/00-1735-0000-0022-5E8F-F
dc.identifier.urihttp://dx.doi.org/10.53846/goediss-4460
dc.language.isodeude
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/3.0/
dc.subject.ddc610de
dc.titleB-Zell-Pathomechanismen der akuten und chronischen Myositis: Ex-Vivo- und In-Vitro-Untersuchungende
dc.typedoctoralThesisde
dc.title.translatedB cell associated pathomechanisms of acute and chronic myositis: ex vivo and in vitro studiesde
dc.contributor.refereeSchmidt, Jens PD Dr.
dc.date.examination2014-05-06
dc.description.abstractengB-cell-associated pathomechanisms of acute and chronic myositis: ex vivo and in vitro studies Sporadic inclusion body myositis (sIBM) is the most common acquired inflammatory myopathy of elderly people. Pathology includes degenerative and inflammatory mechanisms. Recent studies give evidence of a clonal expansion of B cells. So far it is not clear how muscle fibres are involved in activation and recruitment of B cells and if there is a connection with the accumulation of β-amyloid. In this study mRNA expression of relevant markers for activation and recruitment of B cells (B-cell-activating factor BAFF, a proliferation-including ligand APRIL and the chemokines CXCL-12 and CXCL-13) was analysed in muscle biopsies of patients with sIBM and was compared to muscle biopsies of patients with polymyositis (PM) and muscle dystrophy and to healthy muscle biopsies (n=5 up to 10 per group). Protein expression of the same markers was detected by immunohistochemistry, with the help of immunofluorescent stainings co-localization of B cell activating markers and B cells was analysed. In comparison with controls cytokine-induced expression of the same markers was detected by PCR and immunocytochemistry after stimulating muscle cells in vitro with TNF α, IFN γ, IL 1β or combinations of these cytokines. A significant higher mRNA expression of BAFF as well as a higher mRNA expression of APRIL could be measured in muscle biopsies of patients with sIBM and PM compared to healthy controls. Yet, there was no difference in expression of both markers between biopsies of patients with muscle dystrophy and healthy controls. mRNA of CXCL-12 was overexpressed in sIBM, PM and muscle dystrophy compared to controls. mRNA expression of CXCL-13 was unmodified in muscle biopsies of patients with myositis in comparison with muscle dystrophies and controls. With the aid of immunohistochemistry a significant overexpression of BAFF and a higher expression of CXCL-12 could be detected in muscle fibres of patients with sIBM compared to PM, muscle dystrophies and controls. Some BAFF-positive muscle fibres were in cellular contact to B cells. Protein expression of BAFF and CXCL-12 was unmodified in PM and muscle dystrophies in contrast with controls. PCR and immunocytochemistry showed that interferon γ causes an induction of BAFF and interleukin 1β an induction of CXCL-12 in myoblasts after in vitro stimulation. This data contributes to a better understanding of the pathology of sIBM and supports the thesis that muscle fibres themselves are able to take part in activation and recruitment of B cells. The results support the hypothesis that B-cell-associated pathomechanisms are relevant to sIBM. The marker BAFF could be a new target for future strategies in therapy of sIBM.de
dc.contributor.coRefereeWeber, Martin Prof. Dr.
dc.contributor.thirdRefereeOppermann, Martin Prof. Dr.
dc.subject.gersporadische Einschlusskörpermyositisde
dc.subject.engsIBMde
dc.identifier.urnurn:nbn:de:gbv:7-11858/00-1735-0000-0022-5E8F-F-2
dc.affiliation.instituteMedizinische Fakultätde
dc.subject.gokfullNeurologie - Allgemein- und Gesamtdarstellungen (PPN619876247)de
dc.description.embargoed2014-05-13
dc.identifier.ppn783628439


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