Immunotherapy In Allergic Rhinitis: it’s effect on
immune system
Journal presentation By Dr Sambit Shubham Behera
Purpose of Review
Allergic rhinitis (AR) is a chronic inflammatory immunoglobulin (Ig) E-
mediated disease,type 1 hypersensitivity of the nasal mucosa that can
be triggered by the inhalation of seasonal or perennial allergens.
Typical symptoms include sneezing, rhinorrhea, nasal itching, nasal
congestion and symptoms of allergic conjunctivitis.
Patient may also present with tightness of chest due to subclinical
bronchospasm.
Recent Findings
AR has been shown to reduce work productivity in 36–59% of the patients
with 20% reporting deteriorated job attendance. Moreover, 42% of children
with AR report reduced at-school productivity and lower grades.
Most importantly, AR impacts the patient’s quality of life, due to sleep
deprivation.
However, a proportion of patients fails to respond to conventional
medication and opts for the allergen immunotherapy (AIT), which currently
is the only disease-modifying therapeutic option.
AIT can be administered by either subcutaneous (SCIT) or sublingual (SLIT)
route. Both routes of administration are safe, effective, and can lead to
tolerance lasting years after treatment cessation.
Both innate and adaptive immune responses that contribute to allergic
inflammation are suppressed by AIT.
Innate responses are ameliorated by reducing local mast cell, basophil,
eosinophil, and circulating group 2 innate lymphoid cell frequencies
which is accompanied by decreased basophil sensitivity.
Induction of allergen-specific blocking antibodies, immunosuppressive
cytokines, and regulatory T and B cell phenotypes are key pro-tolerogenic
adaptive immune responses.
Mechanism of
allergic rhinitis
Diagnosis
The diagnosis of AR is made based on clinical symptoms such as
sneezing, rhinorrhea, itchy nose and nasal congestion when there is no
sign of lower respiratory tract infections or anatomic abnormalities of the
nose.
Also when lab findings including a positive prick test and IgE specific
antibody are in favour of allergy, regarding the patients’ history and
clinical examination [3] [4].
Treatment
The treatment of allergic rhinitis initially includes the avoidance of allergens
especially common inhaled allergens.
Indoor allergens such as house dust mites (HDM) especially in bed and house fungi
which grow in damp places besides pets, indoor plants, grass, trees and grass
pollen and other allergenic plants should also be avoided .
Also, certain medications such as oral antihistamines, topical decongestants,
inhaled corticosteroids and in certain cases oral corticosteroids are prescribed .
Immunotherapy with allergens is a therapeutic method in which the allergen is
gradually and with an incremental dose administered resulting in the alleviation of
clinical symptoms and reduced disease severity while preventing disease
progression.
Immunotherapy with allergens has proven efficacy in the treatment of allergic
rhinitis/ asthma and allergy to insect sting.
Today, subcutaneous injection of an allergen (SCIT) is the most common type of
immunotherapy. Several studies have shown desirable clinical efficacy in the single
and combined administration of allergens .
In different studies immunotherapy has resulted in a decrease in the number of
principal cells in allergic responses (eosinophils/basophils and mast cells) and an
increase in IgG4; moreover changes in lymphocytes including a rise in CD8+ and
Treg cells and a decrease in IL4 and IL5 levels has been observed.
It seems that immunotherapy has a major role in the induction of specific Treg cells and that
the induction of tolerance in T lymphocytes is the base of immunotherapy.
The tolerance of peripheral T lymphocytes is recognised by the production of allergen-
specific Treg cells.
In addition to tolerance induction, immunotherapy prevents sensitisation towards new
allergens and allergy progression.
CD4+ Treg-cells are divided into two categories: Natural Treg (nTreg) and Inducible Treg
(iTreg) cells.
Each of these subsets has a specific marker and express their specific receptors which for
nTreg cells include CCR4/GITR/CTLA4/CD62L and for iTreg cells include IL10/TGF-beta.
Natural Treg cells react to autoantibodies which are expressed in the thymus whereas
Inducable Treg cells react towards peripheral antigens which are expressed by dendritic
cells.
Discussion
Immunotherapy with allergens is a slow-process treatment which alters the
immunologic mechanisms of [Link] is administered by giving subcutaneous
injections in diluted forms at weekly [Link] dose is gradually increased till
the optimal level is acheived.
The induction of tolerance in peripheral T lymphocytes resulting in a change in the
immune system pathway from TH2 to Treg cells is the main goal in immunotherapy
which is accompanied by elevated IL10 and TGF beta levels.
Eventually, the production of IL10 will lead to the inhibition of allergen-specific IgE
production and on the other hand will result in IgG4 production.
Sublingual immunotherapy is gaining popolarity in recent days as it can be
administered safely with less risk of anaphylaxis.
References
1. Corren J, Baroody F, Pawankar R. Allergic and non allergic rhinitis. In: Adkinson Jr NF, Bochner BS, Burks AW, Busse WW, Holgate ST, Lemanske RF Jr, et al., editors. Middleton's allergy: principles and practice. 1.8 ed.
USA: Elsevier Health Sciences; 2014. pp. 664–85. [ Google Scholar]
2. Jutel M, Akdis M, Budak F, Aebischer-Casaulta C, Wrzyszcz M, Blaser K, et al. IL-10 and TGF-beta cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy. Eur J
Immunol. 2003;33(5):1205–14. [Link] PMid:12731045. [ PubMed] [Google Scholar]
3. Ciprandi G, De Amici M, Negrini S, Marseglia G, Tosca MA. TGF-βand IL-17 serum levels and specific immunotherapy. International immunopharmacology. 2009;9(10):1247–9. [Link]
PMid:19622397. [PubMed] [Google Scholar]
4. Akdis CA, Akdis M. Mechanisms and treatment of allergic disease in the big picture of regulatory T cells. Journal of Allergy and Clinical Immunology. 2009;123(4):735–46. [Link]
PMid:19348912. [PubMed] [Google Scholar]
5. Till SJ, Francis JN, Nouri-Aria K, Durham SR. Mechanisms of immunotherapy. Journal of Allergy and Clinical Immunology. 2004;113(6):1025–34. [Link] PMid:15208578. [ PubMed] [
Google Scholar]
6. Ziegler SF, Buckner JH. FOXP3 and the regulation of Treg/Th17 differentiation. Microbes and Infection. 2009;11(5):594–8. [Link] PMid:19371792 PMCid: PMC2728495. [ PMC free article]
[PubMed] [Google Scholar]
7. Farid R, Ghasemi R, Baradaran-Rahimi M, Jabbari F, Ghaffari J, Rafatpanah H. Evaluation of six years allergen immunotherapy in allergic rhinitis and allergic asthma. Iranian Journal of Allergy, Asthma and Immunology.
2006;5(1):29–31. PMid:17242501. [PubMed] [Google Scholar]
8. Roncarolo MG, Bacchetta R, Bordignon C, Narula S, Levings MK. Type 1 T regulatory cells. Immunological reviews. 2001;182(1):68–79. [Link] PMid:11722624. [ PubMed] [
Google Scholar]
9. Blaiss MS, editor. Allergic rhinitis: Direct and indirect costs. Allergy and Asthma Proceedings. OceanSide Publications, Inc; 2010. PMCid: PMC2824441. [ PubMed] [Google Scholar]
10. Calderon M, Larenas D, Kleine-Tebbe J, Jacobsen L, Passalacqua G, Eng P, et al. European Academy of Allergy and Clinical Immunology task force report on 'dose–response relationship in allergen?specific
immunotherapy'. Allergy. 2011;66(10):1345–59. [Link] PMid:21707645. [ PubMed] [Google Scholar]
11. Lee JH, Yu HH, Wang LC, Yang YH, Lin YT, Chiang BL. The levels of CD4+CD25+regulatory T cells in paediatric patients with allergic rhinitis and bronchial asthma. Clinical & Experimental Immunology. 2007;148(1):53–
63. [Link] PMid:17349011 PMCid: PMC1868849. [ PMC free article] [PubMed] [Google Scholar]
12. Maggi L, Santarlasci V, Liotta F, Frosali F, Angeli R, Cosmi L, et al. Demonstration of circulating allergen-specific CD4+CD25highFoxp3+T-regulatory cells in both nonatopic and atopic individuals. The Journal of allergy
and clinical immunology. 2007;120(2):429–36. [Link] PMid:17604089. [ PubMed] [Google Scholar]
13. Sabin BR, Saltoun CA, Avila PC. Advances in upper airway diseases and allergen immunotherapy. Journal of Allergy and Clinical Immunology. 2011;127(2):342–50. [Link]
PMid:21281864. [PubMed] [Google Scholar]
14. Matricardi PM, Kuna P, Panetta V, Wahn U, Narkus A. Subcutaneous immunotherapy and pharmacotherapy in seasonal allergic rhinitis: a comparison based on meta-analyses. Journal of Allergy and Clinical Immunology.
2011;128(4):791–9. e6. [PubMed] [Google Scholar]
15. Radulovic S, Jacobson MR, Durham SR, Nouri-Aria KT. Grass pollen immunotherapy induces Foxp3-expressing CD4+CD25+cells in the nasal mucosa. Journal of Allergy and Clinical Immunology. 2008;121(6):1467–72.
[Link] PMid:18423565. [ PubMed] [Google Scholar]
16. Allan SE, Passerini L, Bacchetta R, Crellin N, Dai M, Orban PC, et al. The role of 2 FOXP3 isoforms in the generation of human CD4+Tregs. Journal of Clinical Investigation. 2005;115(11):3276–84.
[Link] PMid:16211090 PMCid: PMC1242190. [ PMC free article] [PubMed] [Google Scholar]
17. Bacchetta R, Gregori S, Roncarolo M-G. CD4+regulatory T cells: Mechanisms of induction and effector function. Autoimmunity reviews. 2005;4(8):491–6. [Link] PMid:16214084. [
PubMed] [Google Scholar]
18. Cantillo JF, Puerta L. [New approaches for allergen-specific immunotherapy] Biomedica: revista del Instituto Nacional de Salud. 2009;30(3):440–53. [PubMed] [Google Scholar]
19. Chatila TA. Role of regulatory T cells in human diseases. Journal of allergy and clinical immunology. 2005;116(5):949–59. [Link] PMid:16275360. [ PubMed] [Google Scholar]
20. Crellin NK, Garcia RV, Levings MK. Flow cytometry-based methods for studying signaling in human CD4+CD25+FOXP3+T regulatory cells. Journal of immunological methods. 2007;324(1):92–104.
[Link] PMid:17582431. [ PubMed] [Google Scholar]
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