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Shortened Telomere Length in Sputum Cells of Bronchiectasis Patients is Associated with Dysfunctional Inflammatory Pathways

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Abstract

Telomere attrition is an established ageing biomarker and shorter peripheral blood leukocyte telomere length has been associated with increased risks of respiratory diseases. However, whether telomere length in disease-relevant sputum immune cells of chronic respiratory disease patients is shortened and which pathways are dysfunctional are not clear. Here we measured telomere length from sputum samples of bronchiectasis and asthmatic subjects and determined that telomere length in sputum of bronchiectasis subjects was significantly shorter (Beta =  − 1.167, PAdj = 2.75 × 10−4). We further performed global gene expression analysis and identified genes involved in processes such as NLRP3 inflammasome activation and regulation of adaptive immune cells when bronchiectasis sputum telomere length was shortened. Our study provides insights on dysfunctions related to shortened telomere length in sputum immune cells of bronchiectasis patients.

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Funding

The study was supported by the A*STAR CDA Grant (C210112020) and the National Medical Research Council, Ministry of Health Clinician-Scientist Individual Research Grant New Investigator Grant (CS-IRG-NIG, CNIG17nov014).

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Authors and Affiliations

  1. Division of Respiratory and Critical Care Medicine, Department of Medicine, National University Hospital, National University Health System, 5 Lower Kent Ridge Road, Singapore, 119074, Singapore

    Hui Fang Lim & Mei Fong Liew

  2. Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Hui Fang Lim, Nadia Suray Tan, Mei Fong Liew & Jianjun Liu

  3. Agency for Science, Technology and Research, Genome Institute of Singapore, 60 Biopolis Street, Singapore, 138672, Singapore

    Roghayeh Dehghan, Yee Yen Sia, Jianjun Liu, Chiea Chuen Khor & Rajkumar Dorajoo

  4. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Science, Isfahan, Iran

    Roghayeh Dehghan

  5. Singapore Immunology Network, Agency for Science, Technology and Research, Singapore, Singapore

    Meixin Shen, Immanuel Kwok & Lai Guan Ng

  6. Department of Diagnostic Radiology, National University Hospital, National University Health System, Singapore, Singapore

    Stella Wei Lee Bee

  7. Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, 169856, Singapore

    Chiea Chuen Khor

  8. School of Biological Sciences, Nanyang Technological University, Singapore, Singapore

    Immanuel Kwok & Lai Guan Ng

  9. State Key Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Sciences & Peking Union Medical College, Tianjin, China

    Lai Guan Ng

  10. Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore

    Lai Guan Ng

  11. Immunology Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine and Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore, 119077, Singapore

    Veronique Angeli

  12. Duke-NUS Medical School Singapore, Health Services and Systems Research, Singapore, Singapore

    Rajkumar Dorajoo

Authors
  1. Hui Fang Lim
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  2. Nadia Suray Tan
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  3. Roghayeh Dehghan
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  4. Meixin Shen
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  9. Chiea Chuen Khor
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  10. Immanuel Kwok
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  11. Lai Guan Ng
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  12. Veronique Angeli
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  13. Rajkumar Dorajoo
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Contributions

RD and HFL conceptualized and contributed to study design. NST, MFL, SWLB, HFL and VA performed patient enrolment, sputum processing and clinical measurements. RD, RD, MS, YYS and IK performed genomic studies. RD, JL, CCK and LGN performed data analysis. RD, HFL and NST drafted the manuscript. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Rajkumar Dorajoo.

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Lim, H.F., Tan, N.S., Dehghan, R. et al. Shortened Telomere Length in Sputum Cells of Bronchiectasis Patients is Associated with Dysfunctional Inflammatory Pathways. Lung 200, 401–407 (2022). https://doi.org/10.1007/s00408-022-00535-0

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  • DOI: https://doi.org/10.1007/s00408-022-00535-0

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