Immunoglobulin E (IgE) can be highly elevated in the airway mucosa independently of IgE serum levels and atopic status. Mostly, systemic markers are assessed to investigate inflammation in airway disease for research or clinical practice. A more accurate but more cumbersome approach to determine inflammation at the target organ would be to evaluate markers locally. We review evidence for local production of IgE in allergic rhinitis (AR) and chronic rhinosinusitis with nasal polyps (CRSwNP). Diagnostic and therapeutic consequences in clinical practice are discussed. We describe that the airway mucosa has the intrinsic capability to produce IgE. Moreover, not only do IgE-positive B cells reside within the mucosa, but all tools are present locally for affinity maturation by somatic hypermutation (SHM), clonal expansion, and class switch recombination to IgE. Recognizing local IgE in the absence of systemic IgE has diagnostic and therapeutic consequences. Therefore, we emphasize the importance of local IgE in patients with a history of AR or CRSwNP.
CRSwNP is characterised by eosinophilic inflammation and local IgE production. The amount of local tissue IgE in CRSwNP is independent of the atopic status and serum IgE of the patient. Moreover patients with CRSwNP and pollen allergy do not show prominent symptoms during season. Four groups of patients (n=48) underwent nasal allergen provocation test for grass pollen. We included 12 patients with allergic rhinitis based on grass allergy, 12 patients with CRSwNP without grass allergy, 12 patients with CRSwNP with grass allergy, and 12 control patients. The diagnosis of grass allergy was based on skin prick test and RAST. The test was positive based on change in nasal airflow measured by active anterior rhinomanometry and symptoms. In annex, VAS scores were performed before and after NAPT. The nasal allergen provocation test was positive in 19 % of the patients with CRSwNP without allergy and in 54% of the patients with CRSwNP with allergy. In contrast 100% of the patients with allergic rhinitis developed a positive provocation test, whereas in the control group 8% of the patients developed a positive provocation test. CRSwNP without allergy did not show a significant increase in VAS scores of complaints. In contrast, allergic rhinitis patients and CRSwNP patients with grass allergy developed a significant increase in nasal obstruction and nasal drip. However, in allergic CRSwNP patient the symptoms after provocation were significantly lower compared to AR patients. This suggests that local IgE present in these patients are functional after allergen provocation with grass pollen. However there is a reduced reactivity after grass pollen stimulation in CRSwNP compared to allergic rhinitis. This reduced reactivity is most likely due to the polyclonality of local IgE or IgG4 blocking activity in CRSwNP.
This article was originally published online on 03 February 2014 Allergic rhinitis has been characterized by an important local mucosal inflammation. Therefore we aimed to measure mucosal immunoglobulins and tryptase in nasal secretions by means of paper filter discs in allergic rhinitis (AR) patients in comparison to controls. The purpose of this study was to evaluate the suitability of this approach for use in future clinical trials. Nasal secretions from 12 patients with AR to grass pollen and 12 healthy controls were collected. Two pre-weighed filter discs were placed bilaterally under direct visualization on the anterior third of the nasal septum. Five minutes later, they were removed and weighted again. After adding 2 ml 0,9% NaCl solution to the discs and centrifugation, the nasal secretions were stored in aliquots at -20°C until analysis. Biomarkers such as total IgE, grass pollen specific (gx3) IgE, total IgG, IgG4 and tryptase were measured. Patients with AR were selected based on symptoms during the grass pollen season and based on a positive skin prick test for grass pollen. Control patients were healthy patients without rhinological or allergic disease and with negative skin prick test to the standard panel of allergens. In nasal secretions of AR patients, significant higher levels of total IgE (43.13 kU/l [2.83-75.36] vs 1.66 kU/l [1.66-3.21] resp., P=0.006), grass pollen specific IgE (14.11 kU/l [2.30-24.56] vs 1.66 kU/l [1.66-1.66] resp., P=0.001) and tryptase (33.67 μg/l [8.28-85.07] vs 8.28 μg/l [8.28-8.28], P=0.032) were found compared to controls. Total IgG levels tend to be lower in AR patients compared to controls (182.62 mg/l [86.04-314.56] vs 256.17 mg/l [192.67-457.25], P=0.288) and the levels of IgG4 were rather similar in both groups (12.87 mg/l [4.79-53.48] vs 16.75 mg/dl [3.36-33.26], P=0.833). We were able to measure different biomarkers of nasal mucosal inflammation in nasal secretions collected by means of paper filter discs. As this approach is considerably less invasive and requires less expertise than nasal biopsy, and as –in this small sample– patients with AR had significant higher levels of total IgE, specific IgE and tryptase compared to healthy controls, this method seems to be suitable for monitoring local mucosal inflammation in allergic rhinitis.
Methods Four groups of patients (n=48) underwent nasal allergen provocation test for grass pollen. We included 12 patients with allergic rhinitis based on grass allergy, 12 patients with CRSwNP without grass allergy, 12 patients with CRSwNP with grass allergy, and 12 control patients. The diagnosis of grass allergy was based on skin prick test and RAST. The test was positive based on change in nasal airflow measured by active anterior rhinomanometry and symptoms. In annex, VAS scores were performed before and after NAPT.
