Last Month's Most Accessed Feature: Asthma at work: Proteomics search for biomarkers

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  • Published: Apr 24, 2018
  • Author: Steve Down
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Work-related asthma

Nasal protein profiling has been used to measure the responses of people exposed to airborne allergens like isocyanates and welding fumes, leading to several candidate biomarkers for work-related asthma.

One of the most common occupational hazards is work-related asthma (WRA) but its source is not always recognised due to the similarity of the symptoms with general allergic asthma. In the majority of cases, estimated to be up to 90%, WRA occurs in coincidence with rhinitis and it has been speculated that both conditions could have similar biological mechanisms that are initiated in the respiratory tract.

It is this supposition that has led scientists in Finland to tackle a little used biological substance, nasal matter, to see if it can yield any molecular clues to the disease which could help scientists understand its onset and progression and identify candidate molecules that could act as biomarkers of WRA. Hille Suojalehto, Irmeli Lindström, Henrik Wolff and Anne Puustinen from the Finnish Institute of Occupational Health and the University of Helsinki assembled a panel comprising healthy people and those suffering from different types of WRA.

Allergies from welding fumes, from exposure to airborne isocyanates (used in resins, coatings and paints) and those attributed to proteins were considered. The protein allergies were tested by skin prick tests and immunoglobulin E measurements and were caused by a variety of sources including flour, animals, storage mites, plants, enzymes and spices.

Nasal cell profiling

Cells were collected from the middle meatus in the nasal cavities of eight subjects in each group using nasal brushes and the proteins were extracted for separation by 2D differential gel electrophoresis. After imaging, about 2500 spots were detected on each gel and those with statistically different abundances between an asthma group and controls were selected for further investigation.

They were digested on the gel with trypsin and the resulting peptides were extracted for analysis by mass spectrometry, searching against the SwissProt human database for protein identification. The 228 selected protein spots yielded 77 different proteins, some being represented by multiple spots on the gels.

Cluster analysis revealed that the protein patterns from the isocyanate and protein groups were similar but that of the welding group was different, resembling more closely that of controls. However, a principal components analysis still placed the four groups in separate quadrants, suggesting that the global variability of nasal cell proteins was influenced by the type of exposure.

The greatest effects on the nasal cell proteins were generated by the protein allergens, 20 proteins being down-regulated and 43 up-regulated, compared with 19 and 12, respectively, for the isocyanate group. Within the welding group there were fewer abundance changes with 11 and 7 proteins down and up-regulated, respectively. The affected proteins were associated principally with processes involving inflammation, calcium signalling, free radical scavenging, oxidative stress response and metabolism.

Allergen-responsive proteins

All of the allergenic groups displayed increased levels of S100A9 whereas S100A8 was raised only in the protein allergen group. The other calcium-binding proteins calcyphosin and annexins A1 and A2 were in lower abundance in the protein and isocyanate groups compared with the controls. The abundance changes of S100A9 and galectin were confirmed by separate immunological experiments.

Proteins involved in redox detoxification that were affected included catalase, which was raised in the protein and isocyanate asthma cases, and S-formylglutathione hydrolase and glutathione synthetase that were lowered in the protein allergy group. The roles and mechanisms of these and other significant proteins involved in inflammatory processes were discussed and compared.

The results show that nasal cell samples can be used to represent human airways and could lead to a fuller understanding of the molecular processes that support the development of asthma by undergoing detailed proteomics studies. These, in turn, will return candidate biomarkers of work-related asthma that will help in its diagnosis and offer a way to monitor its progression and treatment.

Related Links

Allergy 2018, 73, 653-663: "Nasal protein profiles in work‐related asthma caused by different exposures"

Article by Steve Down

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.

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