nach oben

Advances in Therapy

Erschienen in:

02.01.2024 | Original Research

Immune Cell Alterations and PI3K-PKB Pathway Suppression in Patients with Allergic Rhinitis Undergoing Sublingual Immunotherapy

verfasst von: Xinxin Zhang, Geping Wu, Xingkai Ma, Lei Cheng

Erschienen in: Advances in Therapy | Ausgabe 2/2024

Einloggen, um Zugang zu erhalten

Abstract

Introduction

Our prior clinical study assessed the efficacy and safety of sublingual immunotherapy (SLIT) with standardized Dermatophagoides farina drops on patients with allergic rhinitis (AR) while analyzing the characteristics of adverse reactions. This study was conducted to evaluate the immune cell composition alterations in AR patients before and after SLIT, and to comprehensively investigate the role and changes of antigen-specific immune cells associated with treatment efficacy.

Methods

A total of 68 AR patients who completed 12 months of SLIT were included in the study. Before the trial’s initiation and after 1 year of SLIT, 10 ml of venous blood was collected. Peripheral blood mononuclear cells were isolated using the Ficoll gradient method. The mRNA transcriptome was analyzed using an Affymetrix microarray. The proportions of 22 immune cell types were calculated via the CIBERSORTx platform. Correlations between each immune cell type and SLIT were analyzed. PI3K-PKB pathway dysregulation were analyzed using quantitative PCR and Western blot. Flow cytometry was utilized to assess the percentages of Th1 and Th2 cells.

Results

Mono-sensitized AR patients exhibited marked increases in plasma cells, activated memory T cells, regulatory T cells, and activated dendritic cells, while experiencing decreased neutrophils and resting dendritic cells. In poly-sensitized AR patients, the most notable change was an increase in regulatory T cells, coupled with decreased T follicular helper cells, resting dendritic cells, and activated mast cells. These findings indicated that SLIT reshaped immune cell profiles in AR patients, and, notably, the specific changes differed between mono-sensitized and poly-sensitized individuals. Furthermore, SLIT appeared to shift the immune response towards a Th2 decrease profile in both groups. Importantly, suppression of the PI3K-PKB pathway was evidenced as inhibition of PKB phosphorylation and the decrease of glycogen synthase kinase 3 β (GSKβ) and mammalian target of rapamycin (mTOR) expression after SLIT.

Conclusion

Our study has demonstrated that SLIT treatment led to distinct changes in immune cell profiles between mono-sensitized and poly-sensitized AR patients. Furthermore, SLIT appeared to reduce a Th2 immune response, highlighting its efficacy in AR treatment. Importantly, the study revealed the suppression of the PI3K-PKB pathway, shedding light on the immunological mechanisms underlying SLIT’s effectiveness.

Nur mit Berechtigung zugänglich

Bousquet J, Van Cauwenberge P, Khaltaev N, Aria Workshop G, World Health O. Allergic rhinitis and its impact on asthma. J Allergy Clin Immunol. 2001;108:S147-334. https://doi.org/10.1067/mai.2001.118891.CrossRef

Cox LS, Larenas Linnemann D, Nolte H, Weldon D, Finegold I, Nelson HS. Sublingual immunotherapy: a comprehensive review. J Allergy Clin Immunol. 2006;117:1021–35. https://doi.org/10.1016/j.jaci.2006.02.040.CrossRefPubMed

Maloney J, Bernstein DI, Nelson H, Creticos P, Hebert J, Noonan M, Skoner D, Zhou Y, Kaur A, Nolte H. Efficacy and safety of grass sublingual immunotherapy tablet, MK-7243: a large randomized controlled trial. Ann Allergy Asthma Immunol. 2014;112(146–53): e2. https://doi.org/10.1016/j.anai.2013.11.018.CrossRef

Ma X, Zhang Y, Gu X, Wu G, Liu J, Lu J, Yang H. A retrospective cohort study of sublingual immunotherapy with standardized dermatophagoides farinae drops for allergic rhinitis. Adv Ther. 2021;38:2315–22. https://doi.org/10.1007/s12325-021-01686-x.CrossRefPubMed

Bousquet J, Lockey R, Malling HJ. Allergen immunotherapy: therapeutic vaccines for allergic diseases. A WHO position paper. J Allergy Clin Immunol. 1998;102:558–62. https://doi.org/10.1016/s0091-6749(98)70271-4.CrossRefPubMed

Moingeon P, Batard T, Fadel R, Frati F, Sieber J, Van Overtvelt L. Immune mechanisms of allergen-specific sublingual immunotherapy. Allergy. 2006;61:151–65. https://doi.org/10.1111/j.1398-9995.2006.01002.x.CrossRefPubMed

Durham SR, Till SJ. Immunologic changes associated with allergen immunotherapy. J Allergy Clin Immunol. 1998;102:157–64. https://doi.org/10.1016/s0091-6749(98)70079-x.CrossRefPubMed

Francis JN, James LK, Paraskevopoulos G, Wong C, Calderon MA, Durham SR, Till SJ. Grass pollen immunotherapy: IL-10 induction and suppression of late responses precedes IgG4 inhibitory antibody activity. J Allergy Clin Immunol. 2008;121(1120–5): e2. https://doi.org/10.1016/j.jaci.2008.01.072.CrossRef

Kim JH, Yoon MG, Seo DH, Kim BS, Ban GY, Ye YM, Shin YS, Park HS. Detection of allergen specific antibodies from nasal secretion of allergic rhinitis patients. Allergy Asthma Immunol Res. 2016;8:329–37. https://doi.org/10.4168/aair.2016.8.4.329.CrossRefPubMedPubMedCentral

10.

Jones SM, Kim EH, Nadeau KC, Nowak-Wegrzyn A, Wood RA, Sampson HA, Scurlock AM, Chinthrajah S, Wang J, Pesek RD, Sindher SB, Kulis M, Johnson J, et al. Efficacy and safety of oral immunotherapy in children aged 1–3 years with peanut allergy (the Immune Tolerance Network IMPACT trial): a randomised placebo-controlled study. Lancet. 2022;399:359–71. https://doi.org/10.1016/S0140-6736(21)02390-4.CrossRefPubMed

11.

Newman AM, Liu CL, Green MR, Gentles AJ, Feng W, Xu Y, Hoang CD, Diehn M, Alizadeh AA. Robust enumeration of cell subsets from tissue expression profiles. Nat Methods. 2015;12:453–7. https://doi.org/10.1038/nmeth.3337.CrossRefPubMedPubMedCentral

12.

Iinuma T, Okamoto Y, Morimoto Y, Arai T, Sakurai T, Yonekura S, Sakurai D, Hirahara K, Nakayama T. Pathogenicity of memory Th2 cells is linked to stage of allergic rhinitis. Allergy. 2018;73:479–89. https://doi.org/10.1111/all.13295.CrossRefPubMed

13.

Wu G, Zhu H, Wu X, Liu L, Ma X, Yuan Y, Fu X, Zhang L, Lv Y, Li D, Liu J, Lu J, Yu Y, et al. Anti-allergic function of alpha-Tocopherol is mediated by suppression of PI3K-PKB activity in mast cells in mouse model of allergic rhinitis. Allergol Immunopathol (Madr). 2020;48:395–400. https://doi.org/10.1016/j.aller.2019.11.005.CrossRefPubMed

14.

Zhang Y, Zhang Q, Wu X, Wu G, Ma X, Cheng L. Bicalutamide, an androgen receptor antagonist, effectively alleviate allergic rhinitis via suppression of PI3K-PKB activity. Eur Arch Otorhinolaryngol. 2023;280:703–11. https://doi.org/10.1007/s00405-022-07538-w.CrossRefPubMed

15.

Cheng L, Zhou WC. Sublingual immunotherapy of house dust mite respiratory allergy in China. Allergol Immunopathol (Madr). 2019;47:85–9. https://doi.org/10.1016/j.aller.2018.02.008.CrossRefPubMed

16.

Cui L, Li J, Li Y, Xia Z. Long-term efficacy of sublingual mite immunotherapy in monosensitized and polysensitized children with allergic rhinitis: a 7-year prospective study. Int Arch Allergy Immunol. 2019;180:144–9. https://doi.org/10.1159/000500524.CrossRefPubMed

17.

Lin Z, Liu Q, Li T, Chen D, Chen D, Xu R. The effects of house dust mite sublingual immunotherapy in patients with allergic rhinitis according to duration. Int Forum Allergy Rhinol. 2016;6:82–7. https://doi.org/10.1002/alr.21657.CrossRefPubMed

18.

Subspecialty Group of Rhinology EBoCJoOH, Neck S, Subspecialty Group of Rhinology SoOH, Neck Surgery CMA. [Chinese guidelines for diagnosis and treatment of allergic rhinitis]. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 2016;51:6–24. https://doi.org/10.3760/cma.j.issn.1673-0860.2016.01.004.

19.

Wang C, Wang K, Liu S, Qin X, Chen K, Zhang T. Decreased level of osteopontin in children with allergic rhinitis during sublingual immunotherapy. Int J Pediatr Otorhinolaryngol. 2016;81:15–20. https://doi.org/10.1016/j.ijporl.2015.12.001.CrossRefPubMed

20.

Zhang Y, Zhang L. Increasing prevalence of allergic rhinitis in China. Allergy Asthma Immunol Res. 2019;11:156–69. https://doi.org/10.4168/aair.2019.11.2.156.CrossRefPubMed

21.

Liu X, Ng CL, Wang Y. The efficacy of sublingual immunotherapy for allergic diseases in Asia. Allergol Int. 2018;67:309–19. https://doi.org/10.1016/j.alit.2018.02.007.CrossRefPubMed

22.

Pawankar R, Mori S, Ozu C, Kimura S. Overview on the pathomechanisms of allergic rhinitis. Asia Pac Allergy. 2011;1:157–67. https://doi.org/10.5415/apallergy.2011.1.3.157.CrossRefPubMedPubMedCentral

23.

Miyara M, Sakaguchi S. Natural regulatory T cells: mechanisms of suppression. Trends Mol Med. 2007;13:108–16. https://doi.org/10.1016/j.molmed.2007.01.003.CrossRefPubMed

24.

Presser K, Schwinge D, Wegmann M, Huber S, Schmitt S, Quaas A, Maxeiner JH, Finotto S, Lohse AW, Blessing M, Schramm C. Coexpression of TGF-beta1 and IL-10 enables regulatory T cells to completely suppress airway hyperreactivity. J Immunol. 2008;181:7751–8. https://doi.org/10.4049/jimmunol.181.11.7751.CrossRefPubMed

25.

Wilson DR, Lima MT, Durham SR. Sublingual immunotherapy for allergic rhinitis: systematic review and meta-analysis. Allergy. 2005;60:4–12. https://doi.org/10.1111/j.1398-9995.2005.00699.x.CrossRefPubMed

26.

Li B, Zhang X, Sun Z, Xu B, Wu J, Liu H, Han H, Wang L, Wu W. A novel strategy for the treatment of allergic rhinitis: regulating Treg/Th17 and Th1/Th2 balance in vivo by vitamin D. Comput Math Methods Med. 2022;2022:9249627. https://doi.org/10.1155/2022/9249627.CrossRefPubMedPubMedCentral

27.

Joint Task Force on Practice P, American Academy of Allergy A, Immunology, American College of Allergy A, Immunology, Joint Council of Allergy A, Immunology. Allergen immunotherapy: a practice parameter second update. J Allergy Clin Immunol. 2007;120:S25–85. https://doi.org/10.1016/j.jaci.2007.06.019.

28.

Savolainen J, Jacobsen L, Valovirta E. Sublingual immunotherapy in children modulates allergen-induced in vitro expression of cytokine mRNA in PBMC. Allergy. 2006;61:1184–90. https://doi.org/10.1111/j.1398-9995.2006.01206.x.CrossRefPubMed

29.

Romani N, Clausen BE, Stoitzner P. Langerhans cells and more: langerin-expressing dendritic cell subsets in the skin. Immunol Rev. 2010;234:120–41. https://doi.org/10.1111/j.0105-2896.2009.00886.x.CrossRefPubMedPubMedCentral

30.

Valladeau J, Ravel O, Dezutter-Dambuyant C, Moore K, Kleijmeer M, Liu Y, Duvert-Frances V, Vincent C, Schmitt D, Davoust J, Caux C, Lebecque S, Saeland S. Langerin, a novel C-type lectin specific to Langerhans cells, is an endocytic receptor that induces the formation of Birbeck granules. Immunity. 2000;12:71–81. https://doi.org/10.1016/s1074-7613(00)80160-0.CrossRefPubMed

31.

Bykovskaia SN, Shurin GV, Graner S, Bunker ML, Olson W, Thomas R, Shurin MR, Marks S, Storkus WJ, Shogan J. Differentiation of immunostimulatory stem-cell- and monocyte-derived dendritic cells involves maturation of intracellular compartments responsible for antigen presentation and secretion. Stem Cells. 2002;20:380–93. https://doi.org/10.1634/stemcells.20-5-380.CrossRefPubMed

32.

Scadding GW, Shamji MH, Jacobson MR, Lee DI, Wilson D, Lima MT, Pitkin L, Pilette C, Nouri-Aria K, Durham SR. Sublingual grass pollen immunotherapy is associated with increases in sublingual Foxp3-expressing cells and elevated allergen-specific immunoglobulin G4, immunoglobulin A and serum inhibitory activity for immunoglobulin E-facilitated allergen binding to B cells. Clin Exp Allergy. 2010;40:598–606. https://doi.org/10.1111/j.1365-2222.2010.03462.x.CrossRefPubMed

33.

Allam JP, Niederhagen B, Bucheler M, Appel T, Betten H, Bieber T, Berge S, Novak N. Comparative analysis of nasal and oral mucosa dendritic cells. Allergy. 2006;61:166–72. https://doi.org/10.1111/j.1398-9995.2005.00965.x.CrossRefPubMed

34.

Iellem A, Mariani M, Lang R, Recalde H, Panina-Bordignon P, Sinigaglia F, D’Ambrosio D. Unique chemotactic response profile and specific expression of chemokine receptors CCR4 and CCR8 by CD4(+)CD25(+) regulatory T cells. J Exp Med. 2001;194:847–53. https://doi.org/10.1084/jem.194.6.847.CrossRefPubMedPubMedCentral

Titel: Immune Cell Alterations and PI3K-PKB Pathway Suppression in Patients with Allergic Rhinitis Undergoing Sublingual Immunotherapy
verfasst von: Xinxin Zhang
Geping Wu
Xingkai Ma
Lei Cheng
Publikationsdatum: 02.01.2024
Verlag: Springer Healthcare
Erschienen in: Advances in Therapy / Ausgabe 2/2024
Print ISSN: 0741-238X
Elektronische ISSN: 1865-8652
DOI: https://doi.org/10.1007/s12325-023-02747-z

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Immune Cell Alterations and PI3K-PKB Pathway Suppression in Patients with Allergic Rhinitis Undergoing Sublingual Immunotherapy

Abstract

Introduction

Methods

Results

Conclusion

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

15% bedauern gewählte Blasenkrebs-Therapie

Costims – das nächste heiße Ding in der Krebstherapie?

Update Innere Medizin

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Introduction

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2024

Safety of Upadacitinib in Immune-Mediated Inflammatory Diseases: Systematic Literature Review of Indirect and Direct Treatment Comparisons of Randomized Controlled Trials

The Effects of Safinamide in Chinese and Non-Chinese Patients with Parkinson’s Disease

The Effect of PCSK9 Inhibitors on LDL-C Target Achievement in Patients with Homozygous Familial Hypercholesterolemia: A Retrospective Cohort Analysis

Real-World Safety and Effectiveness of an 8-Week Regimen of Glecaprevir/Pibrentasvir in Patients with Hepatitis C and Cirrhosis

Study Protocol of a Randomized Controlled Clinical Trial to Evaluate the Efficacy and Safety of Ropeginterferon Alfa-2b in COVID-19 Patients with Comorbidities

Impact of Elevated Body Mass Index (BMI) on Hedonic Tone in Persons with Post-COVID-19 Condition: A Secondary Analysis

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Erhebliches Risiko für Kehlkopfkrebs bei mäßiger Dysplasie

Nach Herzinfarkt mit Typ-1-Diabetes schlechtere Karten als mit Typ 2?

15% bedauern gewählte Blasenkrebs-Therapie

Costims – das nächste heiße Ding in der Krebstherapie?

Update Innere Medizin