Can Sputum Proteomics Find Biomarkers of Non-Tuberculous Mycobacterial Infection?

In a recent study, researchers identified candidate biomarkers of non-tuberculous mycobacterial (NTM) severity/treatment response using sputum proteomics. The researchers’ findings were detailed in an article recently published in CHEST.

Sputum proteomics is a major means of isolating biomarkers in respiratory disease. For instance, previous research has identified calprotectin as a biomarker of disease severity in cystic fibrosis (CF) and neutrophil extracellular traps and SPLUNC1 as biomarkers of bronchiectasis (BE).

In the current study, investigators assessed more than 600 sputum proteins to determine candidate biomarkers for NTM. Investigators analyzed 95 sputum samples from 55 patients with chronic obstructive pulmonary disease (COPD), BE, and CF. They found that underlying disease and infection with Pseudomonas aeruginosa were the main determinants in NTM sputum protein profiles. In total, 12 proteins were abundant in COPD, BE, and CF, including MPO, AZU1, CTSG, CAT and RNASE3, and 21 proteins were downregulated, such as SCGB1A1, IGFBP2, SFTPB, GC and CFD.

In comparing patients with and without NTM, researchers did not find NTM infection to be associated with significant differences in sputum protein profiles. Two iron-chelation proteins were downregulated in those with severe NTM disease, and NTM was linked to heterogeneous differences in sputum protein profile. Those patients with a reduction in immune response proteins expressed improvement in symptoms.

The investigators concluded that sputum proteomics revealed differences in NTM inflammatory profiles between individuals with CF, BE, and COPD, and that NTM is strongly influenced by the presence of Pseudomonas aeruginosa and other typical bacterial infections. However, they noted, “specific sputum proteins biomarkers could not be identified independently from the underlying chest disease and co-infections.” They stressed that future studies seeking NTM biomarkers were needed that accounted for these factors and included a larger sample of patients.

Disclosure: This research was supported by AstraZeneca, Chiesi, Grifols, Insmed, Janssen, Novartis and Zambon. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Hull RC, Huang JTJ, Barton AK, et al. Sputum proteomics in non-tuberculous mycobacterial lung disease. Chest. Published online on November 24, 2021. doi:10.1016/j.chest.2021.11.014