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Characterization of human plasma depletome from patients with schizophrenia

ABSTRACT: The proteome of blood plasma is an interesting source of biomarkers and a potential way to improve treatment outcomes in psychiatric disorders. But its wide dynamic concentration range makes reducing its complexity necessary. Thus, in proteomic studies, a few of the most abundant proteins are depleted and normally discarded. This high-abundance fraction, called the depletome, however, is a source of potential biomarkers due to nonspecific bindings with low abundance proteins. In this work, we characterized the high-abundance fraction from schizophrenia patients using a shotgun mass spectrometry approach.

INSTRUMENT(S): Synapt MS

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Blood Plasma

SUBMITTER: Licia C. Silva-Costa

LAB HEAD: Daniel Martins-de-Souza

PROVIDER: PXD010273 | Pride | 2019-10-23

REPOSITORIES: Pride

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Project description:Dilated cardiomyopathy (DCM) is a disease of the heart muscle characterized by left ventricular or biventricular dilation and systolic dysfunction. It presents one of the most common causes of heart failure worldwide and also the most common indication for heart transplantation. Despite the discharge treatment possibilities, the outcome of patients with recent onset DCM often remains unpredictable and major adverse events may occur in the first months following the diagnosis. Enhancement in the left ventricular ejection fraction – designed as the left ventricular reverse remodeling (LVRR) – has been considered one of the most important determinants of the improvement and treatment response in the prognosis of DCM. In the present study we performed a comprehensive quantitative proteomic analysis of DCM patients’ plasma samples. First we searched for the differences against healthy control group and found several proteins and biological processes to be significantly regulated. The most DCM up-regulated terms corresponded to inflammatory response, wound healing and complement. Among the most relevant DCM up-regulated proteins were CRP, CD163, AOC3, PF4, IGF2, IGFBP2 and TNC. Down-regulation in DCM samples was observed in the biological processes of blood coagulation and lipid metabolism, both of which present risk factors in cardiovascular diseases. The most relevant down-regulated proteins in DCM were TTN, GSN, FCN3, PON1, PON3, and COMP. In the second part of the study, we observed the clinical fate of the DCM patients one year after admission. We divided them according to their treatment response into subgroups of responders (LVRR+) and non-responders (LVRR-) and searched for proteins that would help to predict the patient’s fate or to elucidate the molecular consequences of the disease progression. The protein with the best prognostic potential was ALDOB, its elevated plasma level was found in patients with worse or fatal outcome. The patients with no or poor treatment response had also up-regulated immunoglobulins and pathways corresponding to immunoglobulin-mediated immune response together with cell adhesion which points to the importance of these processes in the DCM pathology.

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Characterization of human plasma depletome from patients with schizophrenia

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