LINC00632 relates to milder Th1/Th2 imbalance, attenuated nasal symptoms, and better response to therapy in allergic rhinitis patients
Main Article Content
Keywords
allergic rhinitis, LINC00632, nasal symptoms, Th/Th2 imbalance, treatment response
Abstract
Objective: Long intergenic noncoding RNA 00632 (LINC00632) regulates nasal inflammation and CD4+ T cell differentiation into T helper (Th) 2 cells in allergic rhinitis (AR). This study aimed to explore the relationship between LINC00632 and Th1/Th2 balance, and the clinical value of LINC00632 in AR patients.
Methods: In total, 120 AR patients, 20 non-atopic obstructive snoring patients as disease controls (DCs), and 20 healthy controls (HCs) were recruited. Their LINC00632 expressions in peripheral blood mononuclear cells were detected by RT-qPCR.
Results: LINC00632 expression was declined in AR patients compared with DCs and HCs (both P ˂ 0.001). Moreover, LINC00632 could distinguish AR patients from DCs with an area under curve (AUC) of 0.795 (95% confidence interval [CI]: 0.701–0.889), and from HCs with an AUC of 0.895 (95%CI: 0.831–0.960). LINC00632 was positively related to Th1 cells (P = 0.037) and Th1/Th2 axis (P ˂ 0.001) in AR patients. In addition, LINC00632 was inversely associated with Th2 cells (P ˂ 0.001) and interleukin (IL)-4 (P = 0.010) in AR patients. Besides, LINC00632 was negatively related to rhinorrhea score (P = 0.019), itching score (P = 0.008), sneezing score (P = 0.004), and total nasal symptom score (TNSS) (P ˂ 0.001), but no correlation between LINC00632 and congestion score was observed (P = 0.093). During treatment, LINC00632 was elevated, while TNSS score was reduced (both P ˂ 0.001). Furthermore, LINC00632 increment was associated with the reduction of TNSS score during the therapy (P = 0.005).
Conclusion: LINC00632 relates to milder Th1/Th2 imbalance, attenuated nasal symptoms, and better response during 4-week therapy in AR patients.
References
2. Brown T. Diagnosis and management of allergic rhinitis in children. Pediatr Ann. 2019;48(12):e485–e8. 10.3928/19382359-20191111-01
3. Asher MI, Montefort S, Bjorksten B, Lai CK, Strachan DP, Weiland SK, et al. Worldwide time trends in the prevalence of symptoms of asthma, allergic rhinoconjunctivitis, and eczema in childhood: ISAAC phases one and three repeat multicountry cross-sectional surveys. Lancet. 2006;368(9537):733–43. 10.1016/S0140-6736(06)69283-0
4. Kalmarzi RN, Ataee P, Fathollahpour A, Behzadifar M, Moradi M, Sharifian F, et al. The prevalence of allergic rhinitis among iranian children: a systematic review and meta-analysis. Endocr Metab Immune Disord Drug Targets. 2020;20(2):189–97. 10.2174/1871530319666190515100735
5. Nam JS, Hwang CS, Hong MP, Kim KS. Prevalence and clinical characteristics of allergic rhinitis in the elderly Korean population. Eur Arch Otorhinolaryngol. 2020;277(12):3367–73. 10.1159/000525595
6. Bousquet J, Hellings PW, Agache I, Amat F, Annesi-Maesano I, Ansotegui IJ, et al. Allergic rhinitis and its impact on asthma (ARIA) phase 4 (2018): change management in allergic rhinitis and asthma multimorbidity using mobile technology. J Allergy Clin Immunol. 2019;143(3):864–79. 10.1016/j.jaci.2018.08.049
7. Vizuete JAC, Sastre J, Bernal ADC, Picado C, Moragon EM, Garcia JMI, et al. Asthma, rhinitis, and nasal polyp multimorbidities. Arch Bronconeumol. 2019;55(3):146–55. 10.1016/j.arbres.2018.09.001
8. Kou W, Li X, Yao H, Wei P. Meta-analysis of the comorbidity rate of allergic rhinitis and asthma in Chinese children. Int J Pediatr Otorhinolaryngol. 2018;107:131–4. 10.12932/ap-120417-0072
9. Agnihotri NT, McGrath KG. Allergic and nonallergic rhinitis. Allergy Asthma Proc. 2019;40(6):376–9. 10.2500/aap.2019.40.4251
10. Dierick BJH, van der Molen T, Flokstra-de Blok BMJ, Muraro A, Postma MJ, Kocks JWH, et al. Burden and socioeconomics of asthma, allergic rhinitis, atopic dermatitis and food allergy. Expert Rev Pharmacoecon Outcomes Res. 2020;20(5):437–53. 10.1080/14737167.2020.1819793
11. Schuler Iv CF, Montejo JM. Allergic rhinitis in children and adolescents. Pediatr Clin North Am. 2019;66(5):981–93. 10.1016/j.pcl.2019.06.004
12. Li W, Cai CY, Zeng JJ. Mesenchymal stem cell-derived exosome-containing Linc00632 regulates GATA binding protein-3 expression in allergic rhinitis by interacting with enhancer of zeste homolog 2 to inhibit T helper cell 2 differentiation. Int Arch Allergy Immunol. 2022;183(2):235–45. 10.1155/2022/4428617
13. Yue L, Yin X, Hao F, Dong J, Ren X, Xu O, et al. Long noncoding RNA Linc00632 inhibits interleukin-13-induced inflammatory cytokine and mucus production in nasal epithelial cells. J Innate Immun. 2020;12(1):116–28. 10.1159/000500420
14. Liva GA, Karatzanis AD, Prokopakis EP. Review of rhinitis: classification, types, pathophysiology. J Clin Med. 2021;10(14):3138.
15. Cheng L, Chen J, Fu Q, He S, Li H, Liu Z, et al. Chinese Society of Allergy Guidelines for Diagnosis and Treatment of Allergic Rhinitis. Allergy Asthma Immunol Res. 2018 Jul;10(4):300-53. 10.3390/jcm10143183
16. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 2001;25(4):402–8. 10.1006/meth.2001.1262
17. Jourdy Y, Chatron N, Carage ML, Fretigny M, Meunier S, Zawadzki C, et al. Study of six patients with complete F9 deletion characterized by cytogenetic microarray: role of the SOX3 gene in intellectual disability. J Thromb Haemost. 2016;14(10):1988–93. 10.1111/jth.13430
18. Barrett SP, Parker KR, Horn C, Mata M, Salzman J. ciRS-7 exonic sequence is embedded in a long non-coding RNA locus. PLoS Genet. 2017;13(12):e1007114. 10.1371/journal.pgen.1007114
19. Jakobsen T, Dahl M, Dimopoulos K, Gronbaek K, Kjems J, Kristensen LS. Genome-wide circular RNA expression patterns reflect resistance to immunomodulatory drugs in multiple myeloma cells. Cancers. 2021;13(3):365. 10.3390/cancers13030365
20. Dong J, Xu O, Wang J, Shan C, Ren X. Luteolin ameliorates inflammation and Th1/Th2 imbalance via regulating the TLR4/NF-kappaB pathway in allergic rhinitis rats. Immunopharmacol Immunotoxicol. 2021;43(3):319–27. 10.1080/08923973.2021.1905659
21. Piao CH, Song CH, Lee EJ, Chai OH. Saikosaponin A ameliorates nasal inflammation by suppressing IL-6/ROR-gammat/STAT3/IL-17/NF-kappaB pathway in OVA-induced allergic rhinitis. Chem Biol Interact. 2020;315:108874. 10.3389/fimmu.2022.856694
22. Han X, Krempski JW, Nadeau K. Advances and novel developments in mechanisms of allergic inflammation. Allergy. 2020;75(12):3100–11. 10.1111/all.14632
23. Nur Husna SM, Tan HT, Md Shukri N, Ashari NSM, Wong KK. Nasal epithelial barrier integrity and tight junctions disruption in allergic rhinitis: overview and pathogenic insights. Front Immunol. 2021;12:663626. 10.3389/fimmu.2021.663626
24. Steelant B, Seys SF, Van Gerven L, Van Woensel M, Farre R, Wawrzyniak P, et al. Histamine and T helper cytokine-driven epithelial barrier dysfunction in allergic rhinitis. J Allergy Clin Immunol. 2018;141(3):951–63. 10.1016/j.jaci.2017.08.039
25. Tomazic PV, Lang-Loidolt D. Current and emerging pharmacotherapy for pediatric allergic rhinitis. Expert Opin Pharmacother. 2021;22(7):849–55. 10.1080/14656566.2020.1808622
26. Linton S, Burrows AG, Hossenbaccus L, Ellis AK. Future of allergic rhinitis management. Ann Allergy Asthma Immunol. 2021;127(2):183–90. 10.1016/j.anai.2021.04.029
27. Breiteneder H, Peng YQ, Agache I, Diamant Z, Eiwegger T, Fokkens WJ, et al. Biomarkers for diagnosis and prediction of therapy responses in allergic diseases and asthma. Allergy. 2020;75(12):3039–68. 10.1111/all.14582