Journal of Mucosal Immunology Research
Open Access

Omalizumab; Allergic reaction; Anaphylaxis

Introduction

Food-dependent exercise-induced anaphylaxis (FDEIA) is a subtype of IgE-mediated food allergies in which in addition to consuming the offending foods, exercise or other secondary causes can also trigger allergic symptoms. 1 More than 60% of the meals that cause FDEIA in adults are made of wheat. Anaphylactic shock is a common occurrence in FDEIA patients, hence avoiding the offending foods is typically advised in these situations. There isn’t a proven effective treatment for FDEIA at the moment [1-3].

Methods

Six locations in Japan—Shimane University Hospital, Hiroshima University Hospital, Kobe University Hospital, Tokyo Medical and Dental University Hospital, Hyogo Prefectural Kakogawa Medical Center, and Okabe Allergy Clinic—completed a phase 2, multicentre single-arm trial. The participants with WDEIA either met the diagnostic criteria established by the Health Labor Sciences Research Grant research group or the Special Committee for the Safety of Protein Hydrolysate in Cosmetics5 (diagnosis of HWP-WDEIA was granted) (diagnosis of CO-WDEIA was given) more than 20 years old; avoiding wheat products due to a history of anaphylaxis following wheat intake within a year; or having positive results from an IgE test performed during the last four weeks against wheat and/or gluten [4-8]. At the time of enrollment, we received participants’ written informed permission. The study received clearance from Shimane University’s ethical committee and the dean of the faculty of medicine (approval number 1945), and it was preregistered with a public registry (UMIN 000019250).

Omalizumab administration dosage

According to the prescribed administration protocol for omalizumab for bronchial asthma, the patients received 150-600 mg of omalizumab (Xolair®, Novartis Pharma, Tokyo, Japan) by subcutaneous administration 12 times at four-week intervals or 24 times at two-week intervals (Supplementary Table 2). During the course of omalizumab treatment, assessments (BAT and blood examination) were carried out at regular intervals (0, 12, 20, 28, 36, and 44 weeks), and they were followed up with routine observations (at 48, 52, 56, 60, 64, and 68 weeks) [9].

Test for basophil activation

Using peripheral blood basophils, a basophil activation test (BAT) based on allergen-induced CD203c expression was carried out. 7, 8, 9 HWP (final concentrations of 0.1 and 1 g/mL), PBS soluble fraction of wheat protein (final concentrations of 1 and 10 g/mL), ethanol extraction fraction of wheat protein (final concentrations of 1 and 10 g/ mL), alkali extraction fraction of wheat protein (final concentrations of 1 and 10 g/mL), and purified -5 gliadin (final concentrations of 0.1 and 1 g/mL) were the activation agents Fluorescence-activated cell sorting was used to track CD203c expression on the basophil surface following activation with these substances [10]. The final figure was represented as a percentage of the activation rate after comparison with anti-IgE activation.

Discussion

Malizumab was demonstrated to be secure and efficient for adult patients with WDEIA in the primary endpoint and the secondary endpoint of this single-arm open study of long-term omalizumab medication. The percentage of patients who attained an activation rate below 10% in CD203c expression-based BAT, an objective metric to assess sensitization circumstances in IgE-mediated allergy, served as the primary outcome. Based on our earlier discovery that patients with wheat allergy had activation rates more than 10% on CD203c expression-based BAT, but patients who were tolerant to wheat displayed activation rates lower than 10%, the activation rate was set to be less than 10%. 9 Moreover, during CD203c expression-based BAT, patients with HWP-WDEIA and CO-WDEIA showed different reaction patterns. This outcome is very consistent with what we had previously noticed. This outcome is consistent with our earlier finding that CO-WDEIA patients primarily reacted to pure -5 gliadin but not to HWP, whereas HWP-WDEIA patients largely reacted to HWP.

Conclusion

Since more than 80% of the patients achieved basophil activation below 10% with all four wheat preparations in the present study, it was clear that the present long-term open study had a greater inhibitory effect on basophil activation with wheat preparations than our previous pilot study using short-term 150 mg fixed dose omalizumab. These findings suggest that the dose and duration of omalizumab treatment are crucial elements for obtaining effective basophil/mast cell suppression of wheat allergen sensitization. Also, the current study showed that omalizumab is effective for treating HWP-WDEIA, which involves sensitised percutaneous and/or rhino-conjunctival pathways, and CO-WDEIA, which is thought to include sensitization through the gastrointestinal system. The lack of an omalizumab randomised placebo-controlled study and the small number of patients included are two drawbacks of our current investigation.

In conclusion, this study shows the effectiveness and safety of omalizumab when administered in accordance with the administration guidelines for Xolair for bronchial asthma. It also offers important information on the treatment of adult patients with WDEIA who avoid eating wheat.

1. Dawood MAO (2016) Immune responses and stress resistance in red sea bream, Pagrus major, after oral administration of heat-killed Lactobacillus plantarum and vitamin C. Fish Shellfish Immunol 54: 266-275.

Indexed at, Google Scholar, Crossref

2. Lalwani S, Sahni G, Mewara B, Kumar R. (2020) Predicting optimal lockdown period with parametric approach using three-phase maturation SIRD model for COVID-19 pandemic. Chaos, Solitons & Fractals 138: 109939.

Indexed at, Google Scholar, Crossref

3. Shereen M A, Suliman K, Abeer K, Nadia B, Rabeea S (2020) COVID-19 Infection: Origin, Transmission, and Characteristics of Human Coronaviruses. J Adv Res 24: 91-98.

Indexed at, Google Scholar, Crossref

4. Damiano P, Francesco D G, Claudia M, Mario A, Vincenzo R, et al.(2020) Coronavirus Diseases (COVID-19) Current Status and Future Perspectives: A Narrative Review. IJERPH 17: 2690.

Indexed at, Google Scholar, Crossref

5. Parikh A P, Binoy V S, Ajay G P, Amruta C V (2020) COVID-19 Pandemic: Knowledge and Perceptions of the Public and Healthcare Professionals. Cureus 12:144.

Indexed at, Google Scholar, Crossref

6. Fine PEM (1995) Variation in protection by BCG: implications of and for heterologous immunity. Lancet 346:1339-1345.

             Indexed at, Google Scholar, Crossref

7. Fallahi-Sichani M, Flynn JL, Linderman JJ, Kirschner DE (2012) Differential risk of tuberculosis reactivation among anti-TNF therapies is due to drug binding kinetics and permeability and not apoptotic and cytolytic activities. J Immun J 188: 3169-3178.

             Indexed at, Google Scholar, Crossref

8. Marino S, El-Kebir M, Kirschner DE (2011) A hybrid multi-compartment model of granuloma formation and T cell priming in Tuberculosis. J Theor Biol 280: 50-62.

             Indexed at, Google Scholar, Crossref

9. Fallahi-Sichani M, El-Kebir M, Marino S, Kirschner DEK, Linderman J (2011) Multi-scale computational modeling reveals a critical role for TNF receptor 1 dynamics in tuberculosis granuloma formation. J Immun J 186: 3472-3483.

             Indexed at, Google Scholar, Crossref

10. Choi SH (2019) Hypoxia-induced rela/p65 derepresses slc16a3 (mct4) by downregulating zbtb7a. Biochim Biophys   Acta Gene Regul Mech 1862:771-785.

             Indexed at, Google Scholar, Crossref