Evaluation of the concentration dynamics of allergen-specific secretory immunoglobulin A in saliva, interleukin 4 and interferon γ in blood serum as predictive biomarkers of the allergen immunotherapy efficacy



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Abstract

BACKGROUND: The only pathogenetic method for treatment of respiratory allergic diseases is allergen immunotherapy. Despite the fact that this method has been used for over a hundred years, its exact mechanisms continue to be studied, and predictive biomarkers that could optimize the selection of patients for therapy are lacking.

AIM: To assess the clinical significance of changes in the levels of allergen-specific secretory immunoglobulin A in saliva, interleukin 4 and interferon γ in blood serum as predictive biomarkers of the allergen immunotherapy efficacy in patients with respiratory allergies.

MATERIALS AND METHODS: A prospective, single-center study included patients with allergic rhinitis with/without asthma caused by sensitization to allergens of house dust mite and healthy volunteers. Patients in the treatment group received therapy with sublingual allergens of house dust mite for six months; the severity of clinical symptoms was assessed at control visits (before, after 2 and 6 months of therapy). Biomaterial was collected once from healthy volunteers and at every control visit from the patients of the treatment group to assess the concentrations of allergen-specific secretory immunoglobulin A in saliva, interleukin 4 and interferon γ in serum using the enzyme-linked immunosorbent assay.

RESULTS: Both treatment and control groups included 10 adult volunteers, matched for age, gender, and baseline cytokine levels (p >0.05). The treatment group had a higher baseline level of allergen-specific secretory immunoglobulin A in saliva (p <0.001). All patients achieved clinical improvement after 6 months of therapy in relation to allergic rhinitis symptoms, patients with asthma achieved improvement after 2 months, this improvement was sustained throughout the observation period. Evaluation of biomarker changes showed a significant increase in the level of allergen-specific secretory immunoglobulin A in saliva by the 2nd month of treatment (p = 0.006), an increase in the concentration of interferon γ in the serum by the 6th month (p = 0.002). The concentration of interleukin 4 in the serum increased by the 2nd (p = 0.002) and decreased by the 6th (p = 0.002) month. The change in the concentration of allergen-specific secretory immunoglobulin A in saliva, interleukin 4 in serum did not correlate with the therapy efficacy, the change in the concentration of interferon γ correlated with the therapy efficacy after 6 months of therapy in relation to symptoms of allergic rhinitis (rs = −0.782; p = 0.012) and asthma (rs = 0.943; p = 0.017).

CONCLUSION: The obtained results indicate that changes in the levels of Th1- and Th2-cytokines in the blood serum, induction of the synthesis of allergen-specific secretory immunoglobulin A in the oral cavity participate in the mechanisms of the sublingual allergen immunotherapy effect. The data of the correlation analysis, assessed at a two-month and six-month interval during allergen immunotherapy, allow us to identify changes in the concentration of interferon γ in the serum as potential predictive biomarker of allergen immunotherapy efficacy.

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About the authors

Daria O. Timoshenko

National Research Center — Institute of Immunology Federal Medical-Biological Agency

Author for correspondence.
Email: d.o.timoshenko@gmail.com
ORCID iD: 0000-0002-7585-1390
SPIN-code: 2714-0906

MD

Россия, Moscow

Oksana M. Kurbacheva

National Research Center — Institute of Immunology Federal Medical-Biological Agency; Russian University of Medicine

Email: kurbacheva@gmail.com
ORCID iD: 0000-0003-3250-0694
SPIN-code: 5698-6436

MD, Dr. Sci. (Medicine), Professor

Россия, Moscow; Moscow

Igor V. Andreev

National Research Center — Institute of Immunology Federal Medical-Biological Agency

Email: iva66@list.ru
ORCID iD: 0000-0001-6162-6726
SPIN-code: 8072-9669

MD, Cand. Sci. (Medicine)

Россия, Moscow

Aleksandr I. Andreev

National Research Center — Institute of Immunology Federal Medical-Biological Agency

Email: cahek_ahdreeb@mail.ru
ORCID iD: 0000-0002-6257-6289
SPIN-code: 7126-4748
Россия, Moscow

Ksenya O. Nechay

Federal Scientific and Clinical Center for Specialized Types of Medical Care and Medical Technologies

Email: xenya.ne4ay2016@yandex.ru
ORCID iD: 0000-0001-6052-9721
SPIN-code: 7206-6660
Россия, Moscow

Mariya V. Khodzhava

National Research Center — Institute of Immunology Federal Medical-Biological Agency

Email: educate.lec@gmail.com
ORCID iD: 0009-0005-5140-1554
SPIN-code: 3046-8033

Cand. Sci. (Pharmacy)

Россия, Moscow

Аleksandr I. Martynov

National Research Center — Institute of Immunology Federal Medical-Biological Agency

Email: immune48@mail.ru
ORCID iD: 0000-0001-9761-8058
SPIN-code: 5829-5580

MD, Cand. Sci. (Medicine)

Россия, Moscow

Natalya I. Ilyina

National Research Center — Institute of Immunology Federal Medical-Biological Agency; The Russian National Research Medical University named after N.I. Pirogov

Email: instimmun@yandex.ru
ORCID iD: 0000-0002-3556-969X
SPIN-code: 6715-5650

MD, Dr. Sci. (Medicine), Professor

Россия, Moscow; Moscow

Musa R. Khaitov

National Research Center — Institute of Immunology Federal Medical-Biological Agency; The Russian National Research Medical University named after N.I. Pirogov

Email: mr.khaitov@nrcii.ru
ORCID iD: 0000-0003-4961-9640
SPIN-code: 3199-9803

MD, Dr. Sci. (Medicine), Professor, Academician of the Russian Academy of Sciences

Россия, Moscow; Moscow

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Supplementary files

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2. Fig. 1. Study design. Note. SLIT — sublingual immunotherapy, HDM — house dust mites, IL — interleukin, IFN — interferon, sIg — secretory immunoglobulin.

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3. Fig. 2. Changes in concentrations of allergen-specific secretory immunoglobulin A (sIgA) during allergen-specific immunotherapy (AIT): a — statistically significant increase in sIgA concentration in saliva by the second month of therapy (p = 0.006); b — statistically significant increase in sIgA concentration in saliva by the sixth month of therapy in relation to base level (p = 0.006); с — statistically significant decrease in sIgA concentration in saliva by the sixth month of therapy relative to the concentration after 2 months of treatment (p = 0.006). Note. CI — confidence interval; V0 — before therapy; V1 — after 8 weeks of therapy; V2 — after 24 weeks of therapy.

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4. Fig. 3. Changes in interleukin (IL) 4 cytokine concentrations during allergen-specific immunotherapy: a — statistically significant increase in IL-4 concentration by the second month of therapy (p = 0.002); b — statistically significant decrease in IL-4 concentration by the sixth month of therapy relative to the concentration after 2 months of therapy (p = 0.002). Note. CI — confidence interval; V0 — before therapy; V1 — after 8 weeks of therapy; V2 — after 24 weeks of therapy.

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5. Fig. 4. Changes in interferon (IFN) γ concentrations during allergen-specific immunotherapy: a — no statistically significant difference in IFN γ concentrations at baseline and after 2 months of therapy (p = 0.107); b — statistically significant increase in IFN γ concentration by the sixth month of therapy relative to the baseline level (p = 0.002). Note. CI — confidence interval; V0 — before therapy; V1 — after 8 weeks of therapy; V2 — after 24 weeks of therapy.

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