Accurately measuring and modeling Th2 and Th17 endotypes in severe asthma

Hart, Kevin M.; Choy, David F.; Bradding, Peter; Wynn, Thomas A.; Arron, Joseph R.

doi:10.21037/atm.2017.02.07

Cited by 7 publications

(4 citation statements)

References 25 publications

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“…The last limitation is the cross-sectional nature of our study preventing driving conclusions on the origin and stability of non-Th2 inflammatory profiles over time [41]. However, this was partially compensated by the detection of viral sequences in RNA sequencing data.…”

Section: Discussionmentioning

confidence: 90%

The “one airway, one disease” concept in light of Th2 inflammation

Giovannini‐Chami¹,

Paquet²,

Sanfiorenzo³

et al. 2018

Eur Respir J

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In line with the pathophysiological continuum described between nose and bronchus in allergic respiratory diseases, we assessed whether nasal epithelium could mirror the Type 2 T-helper cell (Th2) status of bronchial epithelium.Nasal and bronchial cells were collected by brushing from healthy controls (C, n=13), patients with allergic rhinitis and asthma (AR, n=12), and patients with isolated allergic rhinitis (R, n=14). Cellular composition was assessed by flow cytometry, gene expression was analysed by RNA sequencing and Th2, Type 17 T-helper cell (Th17) and interferon (IFN) signatures were derived from the literature.Infiltration by polymorphonuclear neutrophils (PMN) in the nose excluded 30% of the initial cohort. All bronchial samples from the AR group were Th2-high. The gene expression profile of nasal samples from the AR group correctly predicted the paired bronchial sample Th2 status in 71% of cases. Nevertheless, nasal cells did not appear to be a reliable surrogate for the Th2 response, in particular due to a more robust influence of the IFN response in 14 out of 26 nasal samples. The Th2 scores in the nose and bronchi correlated with mast cell count (both p<0.001) and number of sensitisations (p=0.006 and 0.002), while the Th17 scores correlated with PMN count (p=0.006 and 0.003).The large variability in nasal cell composition and type of inflammation restricts its use as a surrogate for assessing bronchial Th2 inflammation in AR patients.

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Section: Discussionmentioning

confidence: 90%

The “one airway, one disease” concept in light of Th2 inflammation

Giovannini‐Chami¹,

Paquet²,

Sanfiorenzo³

et al. 2018

Eur Respir J

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“…In contrast to sarcoidosis, the inflammatory processes in asthma are located to the intima rather than to the interstitium, and while sarcoidosis has both Th1 and Th17 immune responses, asthma is preliminarily considered as a Th2 disease. However, in SA, Th17 responses can also be present [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Altered Fc galactosylation in IgG₄is a potential serum marker for chronic lung disease

et al. 2018

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Characterising chronic lung diseases is challenging. New, less invasive diagnostics are needed to decipher disease pathologies and subphenotypes. Fc galactosylation is known to affect IgG function, and is altered in autoimmune disorders and under other pathological conditions. We tested how well Fc glycans in IgG from bronchoalveolar lavage fluid (BALF) and serum correlated, and if the Fc glycan profile could reveal pulmonary inflammation.A shotgun proteomics approach was used to profile Fc glycans in serum and BALF of controls (n=12) and sarcoidosis phenotypes (Löfgren's syndrome (LS), n=11; and non-LS, n=12). Results were further validated in severe asthma (SA) (n=20) and published rheumatoid arthritis (RA) patient data (n=13) including clinical information.Intra-individually, Fc-galactosylation status of IgG1 (R2=0.87) and IgG4 (R2=0.95) correlated well between matrixes. Following GlycoAge-index correction, the ratio between agalactosylated and digalactosylated Fc glycans of IgG4 could distinguish sarcoidosis and SA from healthy and RA subjects with a mean±se area under the curve (AUC) of 78±6%. The AUC increased to 83±6% using the more chronic lung disease types (non-LS and SA) and most strikingly, to 87±6% for the SA subgroup.The results indicate that the Fc galactosylation status of IgG4 is a potential blood test marker for chronic lung inflammation.

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“…The majority of people with T2 asthma respond well to standard treatment with inhaled corticosteroids whereas individuals with T17 asthma are usually less responsive [2,4,5]. Non-invasive monitoring of local immune mechanisms in asthma remains challenging, but there is a need to identify and better understand such mechanisms in order to develop improved treatment of asthma patient subgroups [6,7].…”

Section: Introductionmentioning

confidence: 99%

T2 and T17 cytokines alter the cargo and function of airway epithelium-derived extracellular vesicles

Jevnikar

Cvjetkovic

et al. 2020

Respir Res

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Background: Asthma is a common and heterogeneous disease that includes subgroups characterized by type 2 (T2) or type 17 (T17) immune responses for which there is a need to identify the underlying mechanisms and biomarkers in order to develop specific therapies. These subgroups can be defined by airway epithelium gene signatures and the airway epithelium has also been implicated to play a significant role in asthma pathology. Extracellular vesicles (EVs) carry functional biomolecules and participate in cell-to-cell communication in both health and disease, properties that are likely to be involved in airway diseases such as asthma. The aim of this study was to identify stimulus-specific proteins and functionality of bronchial epithelium-derived EVs following stimulation with T2 or T17 cytokines. Methods: EVs from cytokine-stimulated (T2: IL-4 + IL-13 or T17: IL-17A + TNFα) human bronchial epithelial cells cultured at air-liquid interface (HBEC-ALI) were isolated by density cushion centrifugation and size exclusion chromatography and characterized with Western blotting and electron microscopy. Transcriptomic (cells) and proteomic (EVs) profiling was also performed. Results: Our data shows that EVs are secreted and can be isolated from the apical side of HBEC-ALI and that cytokine stimulation increases EV release. Genes upregulated in cells stimulated with T2 or T17 cytokines were increased also on protein level in the EVs. Proteins found in T17-derived EVs were suggested to be involved in pathways related to neutrophil movement which was supported by assessing neutrophil chemotaxis ex vivo. Conclusions: Together, the results suggest that epithelial EVs are involved in airway inflammation and that the EV proteome may be used for discovery of disease-specific mechanisms and signatures which may enable a precision medicine approach to the treatment of asthma.

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Accurately measuring and modeling Th2 and Th17 endotypes in severe asthma

Cited by 7 publications

References 25 publications

The “one airway, one disease” concept in light of Th2 inflammation

The “one airway, one disease” concept in light of Th2 inflammation

Altered Fc galactosylation in IgG₄is a potential serum marker for chronic lung disease

T2 and T17 cytokines alter the cargo and function of airway epithelium-derived extracellular vesicles

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Accurately measuring and modeling Th2 and Th17 endotypes in severe asthma

Cited by 7 publications

References 25 publications

The “one airway, one disease” concept in light of Th2 inflammation

The “one airway, one disease” concept in light of Th2 inflammation

Altered Fc galactosylation in IgG4is a potential serum marker for chronic lung disease

T2 and T17 cytokines alter the cargo and function of airway epithelium-derived extracellular vesicles

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Product

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About

Altered Fc galactosylation in IgG₄is a potential serum marker for chronic lung disease