Differential expression of serum/plasma proteins in various infectious diseases: Specific or nonspecific signatures

Abstract

Apart from direct detection of the infecting organisms or biomarker of the pathogen itself, surrogate host markers are also useful for sensitive and early diagnosis of pathogenic infections. Early detection of pathogenic infections, discrimination among closely related diseases with overlapping clinical manifestations, and monitoring of disease progression can be achieved by analyzing blood biomarkers. Therefore, over the last decade large numbers of proteomics studies have been conducted to identify differentially expressed human serum/plasma proteins in different infectious diseases with the intent of discovering novel potential diagnostic/prognostic biomarkers. However, in-depth review of the literature indicates that many reported biomarkers are altered in the same way in multiple infectious diseases, regardless of the type of infection. This might be a consequence of generic acute phase reactions, while the uniquely modulated candidates in different pathogenic infections could be indicators of some specific responses. In this review article, we will provide a comprehensive analysis of differentially expressed serum/plasma proteins in various infectious diseases and categorize the protein markers associated with generic or specific responses. The challenges associated with the discovery, validation, and translational phases of serum/plasma biomarker establishment are also discussed.

A Proteogenomic Analysis of Haptoglobin in Malaria

“…However, downregulation of Hp peptides in dengue fever samples was not significant as compared to malaria (Figure C). The present MRM findings complemented our previous reported iTRAQ data . The precise trends of all three peptide are displayed in Supporting Information, Figure 1.…”

“…Previous proteomics studies from our lab showed that levels of haptoglobin were highly dysregulated in severe malaria cases as compared to non‐severe malaria. Hence, haptoglobin was used for the MRM studies, and three unique peptides were screened.…”

Proteomic analysis of Plasmodium falciparum induced alterations in humans from different endemic regions of India to decipher malaria pathogenesis and identify surrogate markers of severity

“…It is important to emphasize that several serum/plasma proteins, particularly those which are associated with acute phase response signaling cascades, frequently exhibit differential abundant in various diseased conditions [8]. Usually such candidates alone cannot be implemented as reliable diagnostic markers for any specific disease or infection in a general population.…”

“…Indepth analysis of the differential abundances of serum/plasma proteins during the febrile stage of the infection may help in identification of surrogate markers of infection and disease severity and can provide valuable information regarding disease pathogenesis and host immune responses [8,9]. A few previous studies have investigated the alterations in plasma proteome profiles in cerebral falciparum malaria in children from different endemic and holoendemic regions of Africa [10][11][12].…”

Analysis of the plasma proteome using iTRAQ and TMT‐based Isobaric labeling

“…Moreover, since the fundamental processes moderated by the plasma proteome, such as inflammation and coagulation, are concomitant with a range of health disorders, common markers might be expected between similar or related diseases. Accordingly, the observation of the common proteins markers in different cancers and viral infections has been reported . For example, alpha‐1‐acid glycoprotein 1 (ORM1) has been detected in non‐small cell lung cancer and gastric adenocarcinoma, and apolipoprotein A‐IV (APOA4) in ovarian and pancreatic cancers .…”