Serum MicroRNAs 223 and 146a in Allergic Rhinitis Patients as Biomarkers for Efficacy of Sublingual Immunotherapy

Over the last decades the prevalence of allergic disease has steadily been rising and recent figures indicate that in the western world 10-25% of people are affected with allergic diseases ranging from food allergy, atopic dermatitis/ eczema, allergic rhinitis, hay fever to asthma.

Allergic rhinitis (AR) is the most frequent allergic disease in Western Europe that interferes with school attendance and performance, with a prevalence rate of 20-30%. Very few studies of the epidemiology were done about the prevalence of allergic rhinitis in Egypt as its prevalence was 9 %.

Allergic rhinitis is allergen-specific IgE-mediated inflammatory reactions which is characterized by excessive eosinophil infiltration, Th2 cytokine responses such as IL5, IL4, IL13, and mucus secretion. The prevalence of allergic rhinitis is increasing worldwide due to changes in the socioeconomic status, environmental factor, and occupational factor. AR burden on sleep and learning is substantial in children. Moreover, AR is considered a risk factor for subsequent asthma comorbidity.

Allergic rhinitis is characterized by nasal congestion, itching, rhinorrhea, and sneezing, which are manifested as a consequence of inappropriate immune responses mediated by allergen specific immunoglobulin E (IgE) antibodies toward otherwise harmless antigens such as pollen and house dust mite (HDM).

High-sensitivity-C-reactive protein (hs-CRP) is a well-known systemic inflammatory marker that is easy and inexpensive to measure, together with ESR, serum Ig-E and total eosinophil count are measured as laboratory markers of allergic diseases.

MicroRNAs (miRNAs) are small non-coding RNA molecules that are 18-22 nucleotides long and highly conserved throughout evolution. MiRNAs play important roles in numerous disease processes such as asthma and allergic rhinitis and that differential miRNA expression can identify novel subtypes of these diseases. As approximately 150 miRNAs are detectable in the blood, differential miRNA expression patterns may serve as a molecular fingerprint that aids in disease diagnosis, characterization, and prognosis.

MiRNAs may have particular clinical utility in allergic diseases. These diseases are characterized by tissue inflammation and are particularly difficult to diagnose and characterize considering that measuring releasing mediators, such as cytokines in blood which their characteristic measurement is unreliable . As a result, invasive methods (e.g., bronchoscopy and tissue biopsies) are needed to quantify inflammatory changes. It follows that miRNA expression profiling in blood and other body fluids becomes important for identifying and developing novel, non-invasive disease Biomarkers.

One of the most significantly upregulated molecules was miR-223 involved in eosinophilic inflammation and associated with lower regulatory T-cell numbers. It is well known that Treg cells play an important role in development of tolerance by producing IL-10. Thus, in the future inhibition of miR-223 could be considered an adjuvant treatment.

MiR-146a is one of the two members of the miR-146 miR family. It has been reported to be involved in a large number of cell activi¬ties, such as suppression of cancer growth, inhibition of inflam¬mation, regulation of the immune system and suppression of allergic inflammation. MiR-146a play a role in regulation of allergic diseases such as allergic rhinitis by modulating Treg cells.

Allergen-specific immunotherapy (AIT) is currently the only known causal effective treatment of IgE-mediated allergy. Sublingual immunotherapy is a well-established allergen-specific immunotherapy and a safe and effective strategy to reorient inappropriate immune responses in allergic patients.

MiR-146a may play a role in allergen immunotherapy of allergic diseases by modulating Treg cells. Also., high miR-223 expression is associated with lower regulatory T-cell numbers.

Inclusion criteria

• Patient consent.
• Patients between 6-60 years old suffering from allergic rhinitis clinically.
• Positive skin prick test

Exclusion criteria

• 1- Chronic inflammatory condition as COPD, tuberculosis, aspergillosis and chronic hepatitis.

2- Other allergic diseases as bronchial asthma, allergic conjunctivitis and chronic urticaria 3- Those undergoing chronic treatment with systemic steroids or B- blockers 4- Systemic immunological disorders as systemic lupus erythematous, rheumatoid arthritis and systemic sclerosis.

5- Malignancy