Proteomic profiling of peripheral blood mononuclear cells isolated from patients with tuberculosis and diabetes copathogenesis - A pilot study

Abstract

Background Diabetes is an important risk factor for developing tuberculosis. This association leads to exacerbation of tuberculosis symptoms and delayed treatment of both the diseases. Molecular mechanism and biomarkers/drug targets related to copathogenesis of tuberculosis and diabetes are still poorly understood. In this study, proteomics based 2D-MALDI/MS approach was employed to identify host signature proteins which are altered during copathogenesis of tuberculosis and diabetes. Methods Comparative proteome of human peripheral blood mononuclear cells (PBMCs) from healthy controls, tuberculosis and diabetes patients in comparison to comorbid diabetes and tuberculosis patients was analyzed. Gel based proteomics approach followed by in gel trypsin digestion and peptide identification by mass spectrometry was used for signature protein identification. Results Total of 18 protein spots with differential expression in tuberculosis and diabetes copathogenesis (TBDM) patients in comparison to other groups were identified. These proteins belonged to four functional categories i.e. structural, cell cycle/growth regulation, signaling and intermediary metabolism. These include Vimentin, tubulin beta chain protein, Actin related protein 2/3 complex subunit 2, coffilin 1 (Structural), PDZ LIM domain protein, Rho-GDP dissociation inhibitor, Ras related protein Rab (signaling), superoxide dismutase, dCTPpyrophosphatase 1, Transcription initiation factor TFIID subunit 12, three isoforms of Peptidylprolylcis-trans isomerase A, SH3 domain containing protein (metabolism), three isoforms of Protein S100A9 and S100A8 (cell cycle progression/growth regulation). Conclusion Proteins identified to be differentially expressed in TBDM patient can act as potent biomarkers and as predictors for copathogenesis of tuberculosis and diabetes.

Association Between Plasma Exosomes S100A9/C4BPA and Latent Tuberculosis Infection Treatment: Proteomic Analysis Based on a Randomized Controlled Study

“…Of note, S100A9 was upregulated in TB patients, which suggested its damage-associated molecular-pattern features (Kuipers et al, 2013;Scott et al, 2020). Currently, the potential role of varied S100A9 expression as a diagnostic biomarker for TB has been gradually reported (Xu et al, 2015;Kundu et al, 2020;Robak et al, 2022). The high String.org protein-protein interaction network for C4BPA and S100A9.…”

Human peripheral blood mononuclear cells: A review of recent proteomic applications

“…Commonly, centrifugation with 1.077 g mL -1 gradient medium (Ficoll™, Lymphoprep™) is used to isolate PBMCs from the other blood elements. After separation, PBMCs are dispensed in the buffy coat situated between plasma constituting the upper fraction, and the red blood cells and polymorphonuclear leucocytes representing the lower fraction [8][9][10][11][12][13][14][15][16][17][18][19]. When aiming to isolate PBMCs subpopulations/subsets such as CD4+ T cells, magnetic-activated cell sorting (MACS) can be further helpful [20].…”

“…For example, in the 2 studies investigating the PBMCs exposure to low dose radiation [32,33], there were seven proteins or almost half of the proposed candidates in each of the studies that overlapped between the studies exhibiting great reproducibility. Similarly, two studies investigating sepsis [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35] and those investigating diabetes and tuberculosisdiabetes co-pathogenesis [11][12][13][14][15][16][17][18][19][20], also identified mutual candidates.…”

“…After recognition of antigen/body intruder, PBMCs turn from naïve/resting to state, undergoing differentiation and development of effector functions [8][9][10]. Changes associated with inflammation [11], immune-mediated inflammationautoimmune disorders [12,13], genetic pathology towards neurodegeneration [14], mental disorder alternations [15,16], cancer progression [10] or virus-hosting-SARS-CoV-2 pathogenesis [17], are to name a few.…”

The role of pathogens in diabetes pathogenesis and the potential of immunoproteomics as a diagnostic and prognostic tool

“… Molloy et al (2001) used 2DE-PMF to identify the outer membrane proteins of E. coli, S. typhimurium , and K. pneumoniae that are otherwise difficult to identify. Similarly, Kundu et al (2020) performed 2DE-PMF of PBMCs from comorbid DM-tuberculosis patients, identifying 18 protein spots with differential expression. MALDI-TOF based PMF revealed that these overexpressed proteins are involved in cell structure, cell cycle, signaling, and intermediary metabolism.…”