Complement dependence of histamine release in chronic urticaria.

Area of Science:

• Immunology
• Dermatology
• Allergy Research

Background:

• Chronic urticaria (CU) affects 30-45% of patients with IgG autoantibodies targeting the IgE receptor's alpha-subunit.
• The precise mechanism initiating histamine secretion in CU remains unclear.

Purpose of the Study:

• To differentiate between IgE receptor cross-linking and complement activation as triggers for histamine release from cutaneous mast cells.
• To elucidate the role of IgG autoantibodies in chronic urticaria pathogenesis.

Main Methods:

• Human cutaneous mast cells were incubated with patient sera, decomplemented sera, or purified patient IgG.
• IgG was tested with normal serum or complement-deficient sera (C2 or C5 deficient).
• Mast cells were pre-incubated with IgE myeloma to saturate IgE receptors.

Main Results:

• Patient sera induced histamine release, but purified IgG alone did not.
• Patient IgG activated histamine release only in the presence of normal complement (specifically C2 and C5).
• Histamine release was significantly reduced when IgE receptors were saturated with IgE.

Conclusions:

• Mast cell degranulation in CU patients with IgG autoantibodies requires both IgE receptor binding and classical complement cascade activation.
• IgE receptor saturation inhibits IgG-mediated degranulation, likely by preventing IgG binding.
• These findings clarify the pathogenic mechanism in a subset of chronic urticaria patients.