Differences in plasma proteomes for active tuberculosis, latent tuberculosis and non-tuberculosis mycobacterial lung disease patients with and without ESAT-6/CFP10 stimulation

Proteome Science

Temesgen Mohamed¹  Girmay Medhin¹  Mengistu Legesse¹  Biniam Wondale²  Gobena Ameni³  Aboma Zewude⁴  Biruhalem Taye⁵  Takele Teklu⁶  Milkessa Hailemariam⁷  Shiferaw Bekele⁸  Rembert Pieper⁸  Yanbao Yu⁸  Mesfin Tamirat⁹ 

[1] Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia;Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia;Department of Biology, Arba Minch University, Arba Minch, Ethiopia;Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia;Department of Veterinary Medicine, College of Food and Agriculture, United Arab Emirates University, P.O. Box 15551, Al Ain, United Arab Emirates;Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia;Ethiopian Public health Institute, P.O box 1242, Addis Ababa, Ethiopia;Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia;European Molecular Biology Laboratory, Notkestraβe 85, 22607, Hamburg, Germany;Department of Immunology and Molecular Biology, University of Gondar, Gondar, Ethiopia;Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia;Department of Veterinary Laboratory, Ambo University, Guder, Ethiopia;J. Craig Venter Institute, Rockville, MD, USA;Laboratory department, Jinka General Hospital, Jinka, Ethiopia;

关键词: MTBC;    NTM;    Blood plasma;    ESAT-6/CFP-10 antigen cocktail;    Proteomics;    Protein biomarker;    LC-MS/MS;   

DOI  :  10.1186/s12953-020-00165-5

来源: Springer

【 摘 要 】

BackgroundTuberculosis (TB) is one of the world’s most problematic infectious diseases. The pathogen Mycobacterium tuberculosis (Mtb) is contained by the immune system in people with latent TB infection (LTBI). No overt disease symptoms occur. The environmental and internal triggers leading to reactivation of TB are not well understood. Non-tuberculosis Mycobacteria (NTM) can also cause TB-like lung disease. Comparative analysis of blood plasma proteomes from subjects afflicted by these pathologies in an endemic setting may yield new differentiating biomarkers and insights into inflammatory and immunological responses to Mtb and NTM.MethodsBlood samples from 40 human subjects in a pastoral region of Ethiopia were treated with the ESAT-6/CFP-10 antigen cocktail to stimulate anti-Mtb and anti-NTM immune responses. In addition to those of active TB, LTBI, and NTM cohorts, samples from matched healthy control (HC) subjects were available. Following the generation of sample pools, proteomes were analyzed via LC-MS/MS. These experiments were also performed without antigen stimulation steps. Statistically significant differences using the Z-score method were determined and interpreted in the context of the proteins’ functions and their contributions to biological pathways.ResultsMore than 200 proteins were identified from unstimulated and stimulated plasma samples (UPSs and SPSs, respectively). Thirty-four and 64 proteins were differentially abundant with statistical significance (P < 0.05; Benjamini-Hochberg correction with an FDR < 0.05) comparing UPS and SPS proteomic data of four groups, respectively. Bioinformatics analysis of such proteins via the Gene Ontology Resource was indicative of changes in cellular and metabolic processes, responses to stimuli, and biological regulations. The m7GpppN-mRNA hydrolase was increased in abundance in the LTBI group compared to HC subjects. Charged multivesicular body protein 4a and platelet factor-4 were increased in abundance in NTM as compared to HC and decreased in abundance in NTM as compared to active TB. C-reactive protein, α-1-acid glycoprotein 1, sialic acid-binding Ig-like lectin 16, and vitamin K-dependent protein S were also increased (P < 0.05; fold changes≥2) in SPSs and UPSs comparing active TB with LTBI and NTM cases. These three proteins, connected in a STRING functional network, contribute to the acute phase response and influence blood coagulation.ConclusionPlasma proteomes are different comparing LTBI, TB, NTM and HC cohorts. The changes are augmented following prior blood immune cell stimulation with the ESAT-6/CFP-10 antigen cocktail. The results encourage larger-cohort studies to identify specific biomarkers to diagnose NTM infection, LTBI, and to predict the risk of TB reactivation.

【 授权许可】

CC BY