Bamber, Andrew Richard; (2017) A proteomic approach to determining cause of death in sudden unexpected death in infancy (SUDI). Doctoral thesis (M.D(Res)), UCL (University College London).

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Abstract

Introduction: Despite improvements in the understanding of infant death over recent years, many infants die each year in whom no cause of death is identified. There is evidence to suggest that a proportion of these unexplained deaths are the consequence of infection, either by a classical mechanism or as a consequence of the action of bacterial toxins. Post mortem tests for bacteria are robust, but there is a lack of effective post mortem tests for inflammatory markers which might assist in the interpretation of bacteriological results, and for identification of bacterial toxins. Methods: Proteomic techniques including biomarker discovery techniques using liquid chromatography mass spectrometry, and targeted techniques using multiple reaction monitoring tandem mass spectrometry, were used to identify potential biomarkers for infection and identify bacterial organisms and toxins, with a view to creating clinically-useful tests. Results: First, a rapid test for three biomarkers was developed which allows identification of infection and sepsis with high sensitivity and specificity in post mortem liver samples; this may be rapidly translated for clinical use. Second, a highly specific and sensitive test for Staphylococcus aureus and seven Staphylococcal exotoxins was developed which may be used to study the significance of Staphylococcal toxins in infant deaths. Furthermore this technique may adapted to identify other organisms; allowing potential use as a rapid diagnostic test in clinical practice in the living. Thirdly, the tests developed have identified inflammatory markers which are decreased in infants dying of infection; raising the possibility that acquired immune paresis may contribute to these deaths. This finding contributes to the understanding of mechanisms of fatal infection in infants, and in their prevention and management. Finally, a number of mitochondrial proteins have found to be raised in SIDS cases, which may provide additional insight into the mechanism of death in some of these cases.

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