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Assoziation des PDCD1 rs11568821 GG-Genotyps mit stärkerer Morbidität bei Intensivpatienten mit Krankheitsbild Sepsis: Vergleich der SOFA-Sub-Scores

Association of the PDCD1 rs11568821 GG-genotype with higher morbidity of patients with sepsis at ICU: Comparison of the SOFA-sub-scores

Sebastian Gerber
Doctoral thesis
Date of Examination: 2016-06-30
Date of issue: 2016-06-20
Advisor: Mihm, Sabine Prof. Dr.
Referee: Mihm, Sabine Prof. Dr.
Referee: Bickeböller, Heike Prof. Dr.

Persistent Address: http://hdl.handle.net/11858/00-1735-0000-0028-878B-B

 

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Abstract

English

The failing of various therapeutic agents in the treatment of sepsis elucidates the still existing lack of knowledge of this syndrome. Over the last years a major change has taken place as results have shown that, beside a cytokine-storm in an early hyper-inflammatory state, negative co-stimulatory receptors along with a late hypo-inflammatory state play a crucial role in the complex pathophysiology of sepsis. One of these receptors is PD-1, which is encoded by the gene PDCD1. The aim of this study was to illustrate whether a genetic predisposition (PDCD1 rs11568821 GG-genotype), which causes a higher expression of PD-1, accompanies a higher dysfunction of certain organ systems in septic patients. Therefore the PDCD1 rs11568821-genotype and relevant daily parameters as for example the sequential organ failure assessment (SOFA)-score of 300 ICU-patients were examined. Possible confounding variables were excluded. For the first time the results of this study show associations of the PDCD1 rs11568821 GG-genotype with a higher morbidity of CNS, respiration, cardiovascular system and liver present in septic patients. This is expressed by significant higher mean SOFA-sub-scores of respiration, cardiovascular system and CNS for the disease´s process and by prolonged higher mean sub-scores of CNS and cardiovascular system. Additionally none of the A-allele carriers show an acute liver failure in the first days of the disease´s process. Analysises of mortality indicate associations of PDCD1 rs11568821 GG-genotype with a lower survival rate. Consequently associations of a genetic variation in the negative co-stimulatory receptor PD-1´s gene with higher morbidity of chosen organ systems can be perceived. After a validation of these results through an independent collective, the SNP PDCD1 rs11568821 may become a prognostic and predictive factor related to a therapy of sepsis-associated organ dysfunctions while using anti-PD-1-antibodies in the context of advancing personalized medicine.
Keywords: Sepsis; PD-1; PDCD1 rs11568821; morbidity; ICU; SOFA-Score; GG-genotype; cardiovascular system; respiration; CNS
Schlagwörter: Sepsis; PD-1; PDCD1 rs11568821; Morbidität; Intensivstation; SOFA-Score; GG-Genotyp; Herz-Kreislauf-System; Atmung; ZNS
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