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Lymphatic filarial serum proteome profiling for identification and characterization of diagnostic biomarkers.

ABSTRACT: Lymphatic Filariasis (LF) affects more than 863 million people in tropical and subtropical areas of the world, causing high morbidity and long illnesses leading to social exclusion and loss of wages. A combination of drugs Ivermectin, Diethylcarbamazine citrate and Albendazole is recommended by WHO to accelerate the Global Programme to Eliminate Lymphatic Filariasis (GPELF). To assess the outcome of GPELF, to re-evaluate and to formulate further strategies there is an imperative need for high quality diagnostic markers. This study was undertaken to identify Lymphatic Filarial biomarkers which can detect LF infections in asymptomatic cases and would also serve as indicators for differentiating among different clinical stages of the disease. A combination of Fourier-transform infrared spectroscopy (FT-IR), MMP zymography, SDS-PAGE, classical 2DE along with MALDI-TOF/MS was done to identify LF biomarkers from serum samples of different stages of LF patients. FT-IR spectroscopy coupled with univariate and multivariate analysis of LF serum samples, revealed significant differences in peak intensity at 3300, 2950, 1645, 1540 and 1448 cm-1 (p<0.05). The proteomics analysis results showed that various proteins were differentially expressed (p<0.05), including C-reactive protein, α-1-antitrypsin, heterogeneous nuclear ribonucleoprotein D like, apolipoproteins A-I and A-IV in different LF clinical stages. Functional pathway analysis suggested the involvement of differentially expressed proteins in vital physiological pathways like acute phase response, hemostasis, complement and coagulation cascades. Furthermore, the differentiation between different stages of LF cases and biomarkers identified in this study clearly demonstrates the potential of the human serum profiling approach for LF detection. To our knowledge, this is the first report of comparative human serum profiling in different categories of LF patients.

SUBMITTER: Kumar V

PROVIDER: S-EPMC9258881 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundAortic aneurysm is an increasingly common vascular disorder with fatal implication. However, there is no established diagnosis other than that based on aneurysmal size. For this purpose, serum protein biomarkers for aortic aneurysms are valuable. Although most of the studies on serum biomarker discovery have been based on comparison of serum proteins from the patient group with those from the healthy group, we considered that comparison of serial protein profiles such as those in presurgical and postsurgical sera within one patient would facilitate identification of biomarkers since the variability of serial protein profiles within one patient is smaller than that between groups. In this study, we examined serum proteins with differential levels in postsurgery compared with those in presurgery after the removal of aneurysmal tissues in abdominal aortic aneurysm (AAA) and thoracic aortic aneurysm (TAA) patients in order to identify potential serum biomarkers for AAAs and TAAs.ResultsA proteomic approach with an isobaric tag for relative and absolute quantitation (iTRAQ) labeling followed by nano liquid chromatography (nanoLC)-matrix-assisted laser desorption ionization (MALDI)-time of flight (TOF/TOF)-tandem mass spectrometry (MS/MS) was used. In the sera of patients with AAAs and TAAs, a total of 63 and 71 proteins with differential levels were further narrowed down to 6 and 8 increased proteins (≧1.3 fold, postsurgical vs. presurgical) (p < 0.05, patient vs. control) and 12 and 17 decreased proteins (< 0.77 fold, postsurgical vs. presurgical) (p < 0.05, patient vs. control) in postsurgical sera compared with those in presurgical sera, respectively. All of the increased proteins in postsurgical sera of both AAA and TAA patients included several known acute-phase proteins. On the other hand, in the decreased proteins, we found intriguing molecules such as α-2-macroglobulin, gelsolin, kallistatin, and so on. Among them, we confirmed that kallistatin in both AAA and TAA patients and α-2-macroglobulin in TAA patients showed decrease levels in postsurgical sera similar to those in control sera by Western blot analysis with other sera from AAA and TAA patients.ConclusionsTaken together, our findings suggest that Kallistatin and α-2-macroglobulin are potential serum biomarkers for both AAA and TAA and TAA, respectively.

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Lymphatic filarial serum proteome profiling for identification and characterization of diagnostic biomarkers.

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