Diclofenac induces basophil degranulation without increasing CD63 expression in sensitive patients

Area of Science:

• Immunology
• Allergy and Clinical Immunology

Background:

• Diclofenac hypersensitivity involves IgE-independent basophil degranulation.
• CD63 expression on basophils is a proposed in vitro diagnostic marker for drug hypersensitivity.

Purpose of the Study:

• To evaluate diclofenac's ability to induce CD63 basophil expression and degranulation in patients with diclofenac hypersensitivity.
• To compare these responses with IgE-mediated and fMLP-induced basophil activation.

Main Methods:

• Basophil activation test (BAT) using flow cytometry to measure CD63 expression.
• Hereditary basophil degranulation test (HBDT) using toluidine blue staining.
• Stimulation with diclofenac (1 and 10 µg/ml), fMLP, and Dermatophagoides pteronyssinus (Dp) allergen extract.

Main Results:

• Diclofenac induced significant basophil degranulation (HBDT) in susceptible patients (33.62%) compared to controls (8.49%, P=0.0001).
• Diclofenac did not induce significant CD63 expression (BAT) in these patients (2.04%) versus controls (1.93%, P=0.8).
• Patients co-sensitive to Dp showed Dp-specific CD63 expression but responded to diclofenac with degranulation (HBDT).

Conclusions:

• Diclofenac induces basophil degranulation through a mechanism distinct from IgE-mediated or fMLP-induced activation.
• CD63 expression is not a reliable marker for diagnosing diclofenac-induced hypersensitivity.
• Hereditary basophil degranulation test may be more suitable for diagnosing diclofenac allergy.