Impact of Dupilumab on Skin Surface Lipid-RNA Profile in Severe Asthmatic Patients

Overview

Journal Curr Issues Mol Biol

Publisher MDPI

Specialty Molecular Biology

Date 2024 Oct 25

PMID 39451560

Authors

Yoshihiko Sato

Hitoshi Sasano

Sumiko Abe

Yuuki Sandhu

Shoko Ueda

Sonoko Harada

Yuki Tanabe

Kyoko Shima

Tetsuya Kuwano

Yuya Uehara

Takayoshi Inoue

Ko Okumura

Kazuhisa Takahashi

Norihiro Harada

Affiliations

Soon will be listed here.

Abstract

The analysis of skin surface lipid-RNAs (SSL-RNAs) provides a non-invasive method for understanding the molecular pathology of atopic dermatitis (AD), but its relevance to asthma remains uncertain. Although dupilumab, a biologic drug approved for both asthma and AD, has shown efficacy in improving symptoms for both conditions, its impact on SSL-RNAs is unclear. This study aimed to investigate the impact of dupilumab treatment on SSL-RNA profiles in patients with severe asthma. An SSL-RNA analysis was performed before and after administering dupilumab to asthma patients requiring this intervention. Skin samples were collected non-invasively from patients before and after one year of dupilumab treatment. Although 26 patients were enrolled, an SSL-RNA analysis was feasible in only 7 due to collection challenges. After dupilumab treatment, improvements were observed in asthma symptoms, exacerbation rates, and lung function parameters. Serum levels of total IgE and periostin decreased. The SSL-RNA analysis revealed the differential expression of 218 genes, indicating significant down-regulation of immune responses, particularly those associated with type 2 inflammation, suggesting potential improvement in epithelial barrier function. Dupilumab treatment may not only impact type 2 inflammation but also facilitate the normalization of the skin. Further studies are necessary to fully explore the potential of SSL-RNA analysis as a non-invasive biomarker for evaluating treatment response in asthma.

References

Zhang X, Moilanen E, Kankaanranta H . Enhancement of human eosinophil apoptosis by fluticasone propionate, budesonide, and beclomethasone. Eur J Pharmacol. 2000; 406(3):325-32. DOI: 10.1016/s0014-2999(00)00690-7. View

Heaney L, Perez de Llano L, Al-Ahmad M, Backer V, Busby J, Canonica G . Eosinophilic and Noneosinophilic Asthma: An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort. Chest. 2021; 160(3):814-830. DOI: 10.1016/j.chest.2021.04.013. View

Rabe K, Nair P, Brusselle G, Maspero J, Castro M, Sher L . Efficacy and Safety of Dupilumab in Glucocorticoid-Dependent Severe Asthma. N Engl J Med. 2018; 378(26):2475-2485. DOI: 10.1056/NEJMoa1804093. View

Kallieri M, Zervas E, Fouka E, Porpodis K, Hadji Mitrova M, Tzortzaki E . RELIght: A two-year REal-LIfe study of mepolizumab in patients with severe eosinophilic asTHma in Greece: Evaluating the multiple components of response. Allergy. 2022; 77(9):2848-2852. DOI: 10.1111/all.15382. View

Paliwal S, Hwang B, Tsai K, Mitragotri S . Diagnostic opportunities based on skin biomarkers. Eur J Pharm Sci. 2012; 50(5):546-56. DOI: 10.1016/j.ejps.2012.10.009. View

Papi A, Brightling C, Pedersen S, Reddel H . Asthma. Lancet. 2017; 391(10122):783-800. DOI: 10.1016/S0140-6736(17)33311-1. View

Harada N, Makita N, Fukui K, Nishida K, Oneda K, Tashiro N . A Retrospective Claims Database Study to Clarify Disease Burden of Severe Asthma Patients with Type 2 High or Low Inflammation. J Asthma Allergy. 2023; 16:83-93. PMC: 9830705. DOI: 10.2147/JAA.S378505. View

Xu M, Yuan F, Wang S, Xu H, Li C, Tong X . Association of interleukin-18 and asthma. Inflammation. 2016; 40(1):324-327. DOI: 10.1007/s10753-016-0467-3. View

Abdo M, Watz H, Veith V, Kirsten A, Biller H, Pedersen F . Small airway dysfunction as predictor and marker for clinical response to biological therapy in severe eosinophilic asthma: a longitudinal observational study. Respir Res. 2020; 21(1):278. PMC: 7579879. DOI: 10.1186/s12931-020-01543-5. View

10.

Hamada K, Oishi K, Murata Y, Hirano T, Matsunaga K . Feasibility of Discontinuing Biologics in Severe Asthma: An Algorithmic Approach. J Asthma Allergy. 2021; 14:1463-1471. PMC: 8665775. DOI: 10.2147/JAA.S340684. View

11.

Liu M, Chipps B, Munoz X, Devouassoux G, Bergna M, Smith S . Benefit of switching to mepolizumab from omalizumab in severe eosinophilic asthma based on patient characteristics. Respir Res. 2021; 22(1):144. PMC: 8111733. DOI: 10.1186/s12931-021-01733-9. View

12.

Hekking P, Loza M, Pavlidis S, De Meulder B, Lefaudeux D, Baribaud F . Transcriptomic gene signatures associated with persistent airflow limitation in patients with severe asthma. Eur Respir J. 2017; 50(3). DOI: 10.1183/13993003.02298-2016. View

13.

Mummler C, Munker D, Barnikel M, Veit T, Kayser M, Welte T . Dupilumab Improves Asthma Control and Lung Function in Patients with Insufficient Outcome During Previous Antibody Therapy. J Allergy Clin Immunol Pract. 2020; 9(3):1177-1185.e4. DOI: 10.1016/j.jaip.2020.09.014. View

14.

Feng Y, Li M, Yangzhong X, Zhang X, Zu A, Hou Y . Pyroptosis in inflammation-related respiratory disease. J Physiol Biochem. 2022; 78(4):721-737. PMC: 9684248. DOI: 10.1007/s13105-022-00909-1. View

15.

Ishimori A, Harada N, Chiba A, Harada S, Matsuno K, Makino F . Circulating activated innate lymphoid cells and mucosal-associated invariant T cells are associated with airflow limitation in patients with asthma. Allergol Int. 2016; 66(2):302-309. DOI: 10.1016/j.alit.2016.07.005. View

16.

Eger K, Kroes J, Ten Brinke A, Bel E . Long-Term Therapy Response to Anti-IL-5 Biologics in Severe Asthma-A Real-Life Evaluation. J Allergy Clin Immunol Pract. 2020; 9(3):1194-1200. DOI: 10.1016/j.jaip.2020.10.010. View

17.

Dhingra N, Shemer A, Da Rosa J, Rozenblit M, Fuentes-Duculan J, Gittler J . Molecular profiling of contact dermatitis skin identifies allergen-dependent differences in immune response. J Allergy Clin Immunol. 2014; 134(2):362-72. DOI: 10.1016/j.jaci.2014.03.009. View

18.

Nathan R, Sorkness C, Kosinski M, Schatz M, Li J, Marcus P . Development of the asthma control test: a survey for assessing asthma control. J Allergy Clin Immunol. 2004; 113(1):59-65. DOI: 10.1016/j.jaci.2003.09.008. View

19.

Papi A, Ryan D, Soriano J, Chrystyn H, Bjermer L, Rodriguez-Roisin R . Relationship of Inhaled Corticosteroid Adherence to Asthma Exacerbations in Patients with Moderate-to-Severe Asthma. J Allergy Clin Immunol Pract. 2018; 6(6):1989-1998.e3. DOI: 10.1016/j.jaip.2018.03.008. View

20.

Nagase H . Severe asthma in Japan. Allergol Int. 2019; 68(2):167-171. DOI: 10.1016/j.alit.2019.02.004. View