Background
Chronic urticaria (CU) is a skin condition driven by mast cells and basophils. The exact responsiveness profile of these cells, especially regarding the anti‐IgE treatment, Omalizumab, is not fully investigated. We sought to characterize the surface activation profile of basophils in CU during Omalizumab treatment and their responsiveness to IgE and non‐IgE stimulation.
Methods
Whole blood basophils from 11 CU patients and 10 healthy controls were stimulated with either medium, anti‐IgE, fMLP, C5a, or Substance P for 30 min and characterized by flow cytometry.
Results
CU patients showed a broad range of basophil count as opposed to healthy subjects. An increased number of unstimulated CD69+ (p = 0.05), but not CD63+ basophils was observed in CU groups in comparison to healthy. The expression of CD203c and CD200R were comparable between all groups, whilst the FcεRI was reduced with the treatment. Both IgE and non‐IgE mediated stimulations upregulated CD63, CD203c and CD200R, but not CD69 in all groups, however, no difference between the groups was observed. Among unstimulated basophils, expression of MRGPRX2 was higher in CU patients after Omalizumab treatment than in the healthy group (2.4% vs. 1.5%, p = 0.01). The anti‐IgE stimulation increased the number of MRGPRX2‐expressing basophils in the CU group before and after omalizumab as compared to the healthy (p = 0.003; p = 0.005). The fMLP and C5a stimulations showed a similar effect to the IgE‐mediated stimulation. The MRGPRX2 ligand, Substance P did not activate basophils.
Conclusion
CU basophils show increased expression of MRGPRX2 after IgE and non‐IgE stimulation.
Aim: To examine the association between serum levels and
effectiveness of omalizumab in patients with chronic spontaneous
urticaria (CSU), and explore patient-specific factors associated with
omalizumab pharmacokinetics. Methods: Patients with CSU, who
were refractory to high-dose antihistamines and who initiated treatment
with omalizumab (300 mg every four weeks) were eligible for the study.
Treatment was evaluated every 4 week during 12
weeks of treatment with urticaria activity score in the past week (UAS7)
as primary outcome and urticaria control test (UCT), Chronic Urticaria
Quality of Life Questionnaire (CU QoL) and dermatology
life quality index (DLQI) as secondary outcomes. Serum drug level of
omalizumab was measured before (trough level) and at day seven (peak
level) after each injection. Results: A total of 23 patients
were included. After 12 weeks of treatment with omalizumab, an
improvement of 16.8 UAS7 points (95% CI 10.8-22.8), p<0.001
was seen. The omalizumab trough and peak levels were 7.0-33.1 µg/mL and
11.4-54.0 µg/mL and reached a plateau (steady state) after 8-12 weeks of
treatment. Among the patient-specific factors measured at baseline (age,
sex, body mass index (BMI), angioedema, basophil histamine release (HR)
test, blood basophils and eosinophils, and serum total IgE), BMI was the
only significant predictor of omalizumab peak concentrations during the
study (difference -2.75, p<0.05), whereas omalizumab trough
concentrations were significantly associated with UAS7 scores
(difference -0.82, p<0.001). The same was observed for UCT,
DLQI, and CU QoL. Conclusion: In patients with
CSU initiating treatment with omalizumab, a higher BMI predicts lower
peak concentrations of omalizumab during treatment, whereas lower trough
concentrations of omalizumab are associated with a poorer response on
UAS7 and other patient reported outcomes.
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