Large‐scale plasma proteomics can reveal distinct endotypes in chronic obstructive pulmonary disease and severe asthma

Abstract

Background Chronic airway diseases including chronic obstructive pulmonary disease (COPD) and asthma are heterogenous in nature and endotypes within are underpinned by complex biology. This study aimed to investigate the utility of proteomic profiling of plasma combined with bioinformatic mining, and to define molecular endotypes and expand our knowledge of the underlying biology in chronic respiratory diseases. Methods The plasma proteome was evaluated using an aptamer‐based affinity proteomics platform (SOMAscan®), representing 1238 proteins in 34 subjects with stable COPD and 51 subjects with stable but severe asthma. For each disease, we evaluated a range of clinical/demographic characteristics including bronchodilator reversibility, blood eosinophilia levels, and smoking history. We applied modified bioinformatic approaches used in the evaluation of RNA transcriptomics. Results Subjects with COPD and severe asthma were distinguished from each other by 365 different protein abundancies, with differential pathway networks and upstream modulators. Furthermore, molecular endotypes within each disease could be defined. The protein groups that defined these endotypes had both known and novel biology including groups significantly enriched in exosomal markers derived from immune/inflammatory cells. Finally, we observed associations to clinical characteristics that previously have been under‐explored. Conclusion This investigational study evaluating the plasma proteome in clinically‐phenotyped subjects with chronic airway diseases provides support that such a method can be used to define molecular endotypes and pathobiological mechanisms that underpins these endotypes. It provided new concepts about the complexity of molecular pathways that define these diseases. In the longer term, such information will help to refine treatment options for defined groups.

Blood-Based Biomarkers for Eosinophilic Esophagitis and Concomitant Atopic Diseases: A Look into the Potential of Extracellular Vesicles

“…Although less explored, proteins in EVs harbor potential biomarkers for defining asthma endotypes, as hypothesized by Suzuki et al [ 192 ]. Without purification of EVs, the proteome of plasma samples from COPD or patients with severe asthma showed different profiles differentiating each disease and asthma endotypes, significantly enriched in extracellular vesicle markers, and thus suggesting an association between EVs and protein groups [ 192 ].…”

“…Although less explored, proteins in EVs harbor potential biomarkers for defining asthma endotypes, as hypothesized by Suzuki et al [ 192 ]. Without purification of EVs, the proteome of plasma samples from COPD or patients with severe asthma showed different profiles differentiating each disease and asthma endotypes, significantly enriched in extracellular vesicle markers, and thus suggesting an association between EVs and protein groups [ 192 ]. Similarly, a pattern of upregulated (TNFα, IL-4, IL-5, IL-6, IL-17F, CCL2, and CCL17/TARC) and downregulated (IL-11, IL-27, and CCL20) EV-associated cytokines discriminated healthy controls from allergic patients, including asthmatics [ 186 ].…”

Oxidative Stress and Air Pollution: Its Impact on Chronic Respiratory Diseases

“…The methodologies used to identify the molecular biomarkers associated with respiratory diseases are varied and range from the use of proteomics platforms to the use of real-time PCR. In 2021, Suzuki et al evaluated the plasma proteome using an aptamer-base affinity proteomic platform (SOMAscan ® ) in 34 subjects with stable COPD and 51 subjects with asthma, detecting 1238 proteins within which stress markers were found, such as myeloperoxidase (MPO), heme oxygenase 2 (HMOX2), superoxide dismutase (Cu-Zn) (SOD1), peroxiredoxin-1 (PRDX1), and glutathione-S-transferase P1 (GSTP1) [61].…”

APAAACI 2021 International Conference: a new era of allergy and clinical immunology in digital

“…Phenotyping and endotyping allergic diseases are key to the diagnosis and management of severe refractory disease, more commonly in adults than children. This is particularly relevant in disorders of the upper and lower airways (chronic rhinosinusitis with/without nasal polyposis [ 4 ] and severe/ difficult asthma [ 5 ]) and skin (atopic dermatitis [ 6 ] and chronic urticaria [ 7 ]). The patient’s demographic profile, clinical presentation, and clinical course determine the phenotype; whereas biomarkers in the peripheral blood e.g., eosinophils, IgE, Th2 high proinflammatory cytokines e.g., interleukin (IL)-4, IL-5, IL-13, pattern of inflammatory infiltrate within affected tissue e.g., nasal polyps, form the basis of the endotype.…”