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Investigating systemic immune responses in the pathophysiology of allergic rhinitis using peripheral blood

University of British Columbia

Allergic rhinitis (AR) is the most prevalent allergic disease worldwide, affecting up to 40% of the global population. AR is a symptomatic disorder of the nose induced by IgE-mediated allergic inflammation of the nasal mucosa. Many studies have focused on the local inflammatory site contributing to an understanding of the pathophysiology of AR. The systemic immune responses of AR, however, have not been well investigated, and approaches for such investigation are scant. In order to identify systemic immune response signatures, we used peripheral blood collected from subjects with AR following nasal allergen challenge (NAC). The response signatures we identified consist of immune gene clusters associated with frequencies of corresponding immune cells that reflect dynamic immune responses after NAC. In particular, we found individual clusters associated with neutrophils, neutrophil/lymphocyte ratio (NLR), and lymphocytes, which demonstrated significantly different patterns between allergic and non-allergic subjects. The NLR-associated cluster was also moderately associated with clinical symptoms at 6 h post-NAC in cat allergic subjects. We tested how the identified signatures in cat allergy are expressed in birch and ragweed allergies, which are seasonal/intermittent allergies, using the NAC and Environmental Exposure Unit models. In the NAC model, while the birch allergic subjects did not demonstrate significantly (p > 0.05) different total nasal symptom score (TNSS) from the cat allergic subjects, there were fewer significantly (BH-FDR < 0.1) differentially expressed genes after allergen challenge in birch allergy (4 genes) than immune gene signatures (53 genes) identified in cat allergy. The difference may be associated with the distinct clinical symptoms reported between seasonal/intermittent allergy and perennial/persistent allergy. We also used our systemic immune gene signature approach to help determine the possible mechanism of action of the novel immunotherapeutic Cat-PAD. The significant reduction of TNSS that allergic subjects experienced after the immunotherapy was strongly associated with significant increase of lymphocytes at 1 h post-NAC following treatment. As an exploratory data analysis, the approach identified five genes likely associated with the correlation. Collectively, the systemic immune gene signature approach may be a useful and potentially objective method to diagnose AR and investigate the efficacy and mechanisms of AR treatments.

Text

2019-03-30

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/65106

Experimental Medicine

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/