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‣ Natural killer cell transcriptome in patients treated with multi-drug-therapy and host genetic factors influencing leprosy outcome

Marcinek, Patrick
Fonte: Universität Tübingen Publicador: Universität Tübingen
Tipo: Dissertation; info:eu-repo/semantics/doctoralThesis
Relevância na Pesquisa
Leprosy is a bacterial disease of the skin and the nerves, caused by Mycobacterium leprae. Ever since the introduction of a multi-drug therapy in the 1970’s, worldwide incidence has been decreasing and the disease has been eradicated in many countries. However, in recent years occurrence of new cases remains stable at around 200,000 per year. Most new cases are reported in developing countries, and India accounts for more than half of new cases registered every year. In my thesis, I investigated how innate immunity plays an important role in regulating the disease outcome during multi-drug-therapy. This is addressed by examining the transcriptome profile of specific cells of the innate immunity, namely the Natural Killer (NK) cells. Secondly, I investigated innate immunity-associated genes of the human host that are believed to play a significant role in regulating the disease outcome. The thesis is structured into four different chapters. In chapter I of my thesis, published as an original study, I evaluated four specific functional variants in three different genes that are part of the NOD-2 signaling pathway: NOD2 (rs9302752A/G), LRRK2 (rs1873613A/G), and RIPK2 (rs40457A/G and rs42490G/A). I utilized 211 clinically classified Indian leprosy patients with 230 ethnically matched controls. The genetic variants were chosen for their role in innate immunity and because they had been found to be associated to leprosy in an earlier study carried out in a Han Chinese population. The LRRK2 locus proved to be associated with leprosy outcome. The LRRK2 rs1873613A minor allele and respective rs1873613AA genotype were significantly associated with an increased risk whereas the LRRK2 rs1873613G major allele and rs1873613GG genotypes conferred protection. Also...