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<p>Human immunodeficiency virus (HIV) associated tuberculosis (TB) poses significant diagnostic challenges due to atypical clinical presentations and the limited sensitivity of existing tools in detecting the low number of bacilli often present in sputum of HIV-infected individuals. Serum exosomes have emerged as a promising noninvasive source of disease-specific biomarkers; however, the proteomic content of exosomes from patients with HIV–TB coinfection remains poorly explored. The present study aimed to investigate proteomic content of serum exosomes of patients with and without HIV-TB coinfection to identify compositional variability and potential biomarkers for TB in HIV-positive patients. Serum exosomes from patients with HIV-TB coinfection, extrapulmonary TB, HIV monoinfected, pulmonary TB, and healthy controls (n = 30 each) were processed and compared using Sequential Window Acquisition of all Theoretical Fragment-ion spectra-Mass Spectrometry (SWATH-MS). A total of 150 exosomal proteins, including 68 differentially expressed proteins (DEPs), were identified using quantitative proteomic analyses. Among the DEPs, 33 proteins were significantly were significantly differentially expressed in HIV–TB co-infected patients, whereas 4, 25, and 6 proteins were significantly altered in extrapulmonary TB, HIV mono-infected, and pulmonary TB patients, respectively. Comparative proteomic analysis revealed that 13 proteins (AFTPH, ORM1, LPA, SERPINA, IGLV3-25, IGKV1-17, IGHV2-5, IGHV3-35, IGHV3-7, GC, CP, IGLC2, IGHV3OR16-12) were significantly differentially expressed only in HIV-TB co-infected patients. These uniquely DEPs were found most enriched in the pathways of ferroptosis, followed by porphyrin and chlorophyll metabolism, and cholesterol metabolism using bioinformatics tools. In conclusion, significant alterations were identified in protein profiles of serum exosomes of patients with HIV-TB coinfection, pulmonary TB, extra-pulmonary TB and HIV patients as compared to healthy humans, along with uniquely significant DEPs that may serve as biomarkers and enhance understanding of the pathogenesis of TB in HIV-positive patients.</p>

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Quantitative Proteomic Analysis of Serum-Derived Exosomes from Patients with and Without Human Immunodeficiency Virus–Tuberculosis Coinfection

  • 期刊论文

  • 发表日期：

    2026年2月24日

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  • Shweta Kushwaha,
  • Rajbala Yadav,
  • Roopendra Kumar,
  • Anjana Goel,
  • Santosh Kumar,
  • Devendra Singh Chauhan,
  • Ajay Vir Singh

摘要

Human immunodeficiency virus (HIV) associated tuberculosis (TB) poses significant diagnostic challenges due to atypical clinical presentations and the limited sensitivity of existing tools in detecting the low number of bacilli often present in sputum of HIV-infected individuals. Serum exosomes have emerged as a promising noninvasive source of disease-specific biomarkers; however, the proteomic content of exosomes from patients with HIV–TB coinfection remains poorly explored. The present study aimed to investigate proteomic content of serum exosomes of patients with and without HIV-TB coinfection to identify compositional variability and potential biomarkers for TB in HIV-positive patients. Serum exosomes from patients with HIV-TB coinfection, extrapulmonary TB, HIV monoinfected, pulmonary TB, and healthy controls (n = 30 each) were processed and compared using Sequential Window Acquisition of all Theoretical Fragment-ion spectra-Mass Spectrometry (SWATH-MS). A total of 150 exosomal proteins, including 68 differentially expressed proteins (DEPs), were identified using quantitative proteomic analyses. Among the DEPs, 33 proteins were significantly were significantly differentially expressed in HIV–TB co-infected patients, whereas 4, 25, and 6 proteins were significantly altered in extrapulmonary TB, HIV mono-infected, and pulmonary TB patients, respectively. Comparative proteomic analysis revealed that 13 proteins (AFTPH, ORM1, LPA, SERPINA, IGLV3-25, IGKV1-17, IGHV2-5, IGHV3-35, IGHV3-7, GC, CP, IGLC2, IGHV3OR16-12) were significantly differentially expressed only in HIV-TB co-infected patients. These uniquely DEPs were found most enriched in the pathways of ferroptosis, followed by porphyrin and chlorophyll metabolism, and cholesterol metabolism using bioinformatics tools. In conclusion, significant alterations were identified in protein profiles of serum exosomes of patients with HIV-TB coinfection, pulmonary TB, extra-pulmonary TB and HIV patients as compared to healthy humans, along with uniquely significant DEPs that may serve as biomarkers and enhance understanding of the pathogenesis of TB in HIV-positive patients.