Purpose
Detailed understanding of host pathogen interaction in tuberculosis is an important avenue for identifying novel therapeutic targets. Small extracellular vesicles (EVs) like exosomes that are rich in proteins, nucleic acids and lipids, act as messengers and may show altered composition in disease conditions.
Experimental design
In this case control study, small EVs are isolated from serum of 58 subjects (all male, 33 (15–70) in years) including drug naïve active tuberculosis (ATB: n = 22), non‐tuberculosis (NTB: n = 18), and healthy subjects (n = 18). Serum small EVs proteome analysis is carried out using isobaric tag for relative and absolute quantification (iTRAQ) experiments and an independent sample (n = 36) is used for validation.
Results
A set of 132 and 68 proteins are identified in iTRAQ‐I (ATB/Healthy) and iTRAQ‐II (ATB/NTB) experiments, respectively. Four proteins (KYAT3, SERPINA1, HP, and APOC3) show deregulation (log2‐fold change > ±0.48, p < 0.05) in ATB with respect to healthy controls and Western blot data corroborated mass spectrometry findings.
Conclusions and clinical relevance
These important proteins, involved in neutrophil degranulation, plasma heme scavenging, kynurenine, and lipid metabolism, show deregulation in ATB patients. Identification of such a protein panel in circulating small EVs besides providing novel insights into their role in tuberculosis may prove to be useful targets to develop host‐directed therapeutic intervention.
Poster session 1, September 21, 2022, 12:30 PM - 1:30 PM
Objectives
Chronic pulmonary aspergillosis is a slow and progressive lung disease that occurs in apparently immune-competent patients. Pulmonary tuberculosis is considered to be a major predisposing factor. Early diagnosis of the condition can improve morbidity and mortality. As the number of studies to detect this disease in India is sparse, this study was undertaken in District Tuberculosis center attached to Assam Medical College and Hospital, Dibrugarh to find out the occurrence of chronic pulmonary aspergillosis in treated pulmonary TB patients.
Methods
This prospective hospital-based cross-sectional study was done in Assam Medical College and Hospital, Dibrugarh from December 2015-November 2017. Every consecutive pulmonary TB case after completion of intensive therapy attending the outpatient department with respiratory symptoms was included in the study. Cases were identified with clinical, serological/mycological, and radiological criteria.
Results
A total of 26 cases of CPA were confirmed out of 211 enrolled cases. Positivity rate of CPA in the enrolled patients was 12.3% (95% CI 8.19-17.51%). The hospital-based occurrence rate was found to be 6/1000 (95% CI 3.8-8.5) in the outdoor attendants in DTC, Dibrugarh. Most of the cases (88.46%) were late cases presenting with aspergilloma. Majority (51.72%) of the aspergilloma cases were detected within 5 years of diagnosis of PTB. Very few (15.38%, n = 4) early cases were detected. The sensitivity of the ELISA test (DRG, Germany) was found to be 72.72% as compared with reference Immunocap method used in this study. A section (37.90%) of the patients with fungal ball was seronegative by Aspergillus fumigatus serological test. Two of them were positive for Aspergillus flavus in sputum culture.
Conclusion
A serological test to detect Aspergillus flavus IgG may complement the Aspergillus fumigatus IgG test in detecting CPA. CPA is a neglected disease with a high morbidity and mortality. Routine follow-up protocol for the cavitary patients in tuberculosis center by a sensitive serological test for a minimum period of 5 years may be necessary for early detection of cases in PTB high prevalence countries.
Quantitative proteome analysis of serum small extracellular vesicles isolated from healthy controls and drug naive active tuberculosis patients showed altered protein composition. A set of four important proteins (SERPINA1, KYAT3, HP and APOC3) showed deregulation. These important proteins are involved in neutralizing bacterial infection, psychotic symptoms, acute immune response and adipose tissue lipolysis. This is reported by Rakesh Arya, Deepti Dabral, Hossain Md. Faruquee, Himangshu Mazumdar, Saurav Jyoti Patgiri, Trinayan Deka, Rumi Basumatary, Rukuwe‐u Kupa, Chayale Semy, Wetetsho Kapfo, Kevideme Liegise, Inderjeet Kaur, Tenzin Choedon, Purnima Kumar, Rajendra Kumar Behera, Pranjal Deori, Reema Nath, Kerekha Khalo, Lahari Saikia, Vinotsole Khamo, Ranjan Kumar Nanda in article 1900062.
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