Plasma-derived extracellular vesicles discriminate type-1 allergy subjects from non-allergic controls

Abstract

Background Allergies are on the rise globally, with an enormous impact on affected individuals’ quality of life as well as health care resources. They cause a wide range of symptoms, from slightly inconvenient to potentially fatal immune reactions. While allergies have been described and classified phenomenologically, there is an unmet need for easily accessible biomarkers to stratify the severity of clinical symptoms. Furthermore, biomarkers marking the success of specific immunotherapy are urgently needed. Objectives Plasma extracellular vesicles (pEV) play a role in coordinating the immune response and may be useful future biomarkers. A pilot study on differences in pEV content was carried out between patients with type I allergy, suffering from rhinoconjunctivitis with or without asthma, and voluntary non-allergic donors. Methods We examined pEV from 38 individuals (22 patients with allergies and 16 controls) for 38 chemokines, cytokines, and soluble factors using high-throughput data mining approaches. Results Patients with allergies had a distinct biomarker pattern, with 7 upregulated (TNF-alpha, IL-4, IL-5, IL-6, IL-17F, CCL2, and CCL17) and 3 downregulated immune mediators (IL-11, IL-27, and CCL20) in pEV compared to controls. This reduced set of 10 factors was able to discriminate controls and allergic patients better than the total array. Conclusions The content of pEV showed potential as a target for biomarker research in allergies. Plasma EV, which are readily measurable via blood test, may come to play an important role in allergy diagnosis. In this proof-of-principle study, it could be shown that pEV's discriminate patients with allergies from controls. Further studies investigating whether the content of pEVs may predict the severity of allergic symptoms or even the induction of tolerance to allergens are needed.

The functional role of CST1 and CCL26 in asthma development

“…A previous study of cord blood found associations between higher CXCL10 levels in infancy and asthma later in life, contradictory to our findings, but decreased levels of CXCL11 that were associated with allergic sensitization later in life, in line with our study. 85 In plasma extracellular vesicles of allergic patients, CCL20 was among the downregulated biomarkers 86 what is in line with our results. Nevertheless, higher CCL3 concentration in serum could be observed in patients with allergic rhinitis, 87 only seen for the samples overexpressing CST1.…”

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

“…Duarte et al found elevated levels of platelet microparticles in the circulation of a group of 20 asthmatics under corticosteroid treatment compared to 15 healthy volunteers, and further studies showed similar upregulation induced by pollution [ 183 , 184 , 185 ]. Nonetheless, elevated EV levels do not correspond specifically to asthma, as was observed in asthmatics and non-asthmatics from a cohort of type-1 allergic patients with rhinoconjunctivitis [ 186 ].…”

“…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 ].…”

“… Venn diagram showing overlapping circulating biomarkers for BA, AD, BA-EVs, and AD-EVs [ 65 , 66 , 67 , 68 , 83 , 84 , 85 , 101 , 107 , 108 , 138 , 184 , 185 , 186 , 187 , 188 ]. Created with Jvenn diagram viewer [ 173 ].…”

Packaging and Delivery of Asthma Therapeutics

“…These particles, including microvesicles and nanoscale exosomes, are capable of encapsulating the proteins, lipid mediators, and nucleic acids (including miRNA) that play key roles in the development of pathological processes such as allergic asthma [145,146]. Moreover, these vesicles can serve both as biomarkers to help distinguish different types of allergies in patients and as particles to deliver active molecules that suppress further asthmatic pathogenesis and exacerbations [147][148][149].…”