نبذة مختصرة : Persistent immune activation with premature ageing and increased risk of cardiovascular disease (CVD) are features shared by HIV-1 infected individuals and patients with chronic kidney disease (CKD). Underlying dysbiosis, a failing mucosal barrier function and microbial translocation (MT) are contributing factors in both conditions. Vitamin D supplementation might prove valuable by its modulatory effects on innate and adaptive immunity, including induction of antimicrobial peptides (AMPs), regulation of epithelial barrier integrity and gut microbial composition. The main objective of this thesis was to assess gut-derived immune activation and investigate the modulatory effects of vitamin D supplementation in HIV-1. Additionally we wanted to explore Trimethylamine-N-Oxid (TMAO), a microbial metabolite with newly ascribed pro-atherosclerotic properties, as a novel link between gut microbiome and inflammaging in CKD and in HIV-1. In an observational study on HIV-1 infected individuals on antiretroviral treatment (ART) and non-HIV controls, we found that, whereas HIV-1 infected individuals demonstrated increased immune activation in the form of elevated levels of hsCRP and sCD14 with HIV as an independent risk factor, they did not differ from controls in degree of MT measured by LPS. We next assessed the role of TMAO in cross-sectional and retrospective cohorts of CKD and HIV-1 patients of various disease stages. We found that TMAO levels correlated with increased systemic inflammation measured by hsCRP and was an independent predictor of mortality in CKD. TMAO levels were strongly associated with renal function and normalized after renal transplantation. In HIV-1, we found that TMAO levels were lower in untreated HIV-1 and normalized with treatment, but held no association with markers of immune activation or MT. Higher TMAO-levels in well controlled HIV-1 were not significantly associated with cardiovascular events. Nor was TMAO levels clearly associated with gut microbiome, or degree of dysbiosis. Finally, in a ...
Relation: I. Catharina Missailidis, Jonas Höijer, Maria Johansson, Lena Ekström, Göran Bratt,Bo Hejdeman, Peter Bergman. Vitamin D status in well controlled Caucasian HIV-patients in relation to inflammatory and metabolic markers – a cross-sectional cohort study in Sweden. Scandinavian Journal of Immunology. 2015, 82, 55-62. ::doi::10.1111/sji.12299 ::pmid::25833795 ::isi::000356436300006; II. Catharina Missailidis, Jenny Hällqvist, Abdel Rashid Qureshi, Peter Barany, Olof Heimbürger, Bengt Lindholm, Peter Stenvinkel, Peter Bergman. Serum Trimethylamine-N-Oxide is strongly related to renal function and predicts outcome in chronic kidney disease. PloS one. 2016, 11.e.0141738. ::doi::10.1371/journal.pone.0141738 ::pmid::26751065 ::isi::000367888100005; III. Catharina Missailidis, Ujjwal Neogi, Peter Stenvinkel, Marius Troseid, Piotr Nowak, Peter Bergman. The microbial metabolite TMAO in association with inflammation and microbial dysregulation in three HIV cohorts at various disease stage. AIDS. 2018, 32, 1589-1598. ::doi::10.1097/QAD.0000000000001813 ::pmid::29620717 ::isi::000441209600005; IV. Catharina Missailidis, Nikolaj Sørensen, Senait Ashenafi, Wondwossen Amogne, Endale Kassa, Amsalu Bekele, Meron Getachew, Nebiat Gebreselassie, Abraham Aseffa, Getachew Aderaye, Jan Andersson, Susanna Brighenti, Peter Bergman. Vitamin D and phenylbutyrate supplementation does not modulate gut-derived immune activation in HIV-1. [Manuscript]; http://hdl.handle.net/10616/46504
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