Complement dependence of histamine release in chronic urticaria.
BACKGROUND
IgG autoantibodies directed to the alpha-subunit of the IgE receptor have been identified in 30% to 45% of patients with chronic urticaria. However, the exact mechanism by which histamine secretion is initiated is uncertain.


OBJECTIVE
Histamine release from cutaneous mast cells may occur by cross-linking the IgE receptor or by activation of complement. Our goal is to distinguish these 2 possibilities.


METHODS
We incubated human cutaneous mast cells with patient sera, decomplemented sera, or purified patient IgG. The IgG was also added to pooled normal serum or to sera deficient in either C2 or C5, and its ability to activate mast cells was assessed. Mast cells were incubated with human IgE myeloma to saturate alpha-subunits to determine the effect on histamine release.


RESULTS
Patient sera released histamine (18.26% +/- 4.39%), but purified IgG from patients (5.5% +/- 4.3%) did not. Addition of the patient IgG to normal sera rendered the sera positive for histamine-releasing activity (18.4% +/- 4.3%), whereas control IgG or patient IgG added to C2- or C5-deficient sera did not release histamine. Histamine release with decomplemented patient sera was also diminished (8.34% +/- 4.3%). Preincubation of mast cells with a C5-blocking peptide decreased histamine release but was not statistically significant; there was a significant decrease after preincubating mast cells with IgE myeloma.


CONCLUSIONS
The degranulation of mast cells by IgG autoantibodies in patients with chronic urticaria requires binding to the IgE receptor and activation of the classical complement cascade. Saturation of the IgE receptor with IgE inhibits such degranulation, presumably by preventing binding of the requisite IgG.
Asthma and Allergy Center, Division of Pulmonary Diseases, Department of Medicine, Medical University of South Carolina, Charleston, USA.
M
M
Ferrer
K
K
Nakazawa
A P
AP
Kaplan
D015550:Cell Degranulation; D002908:Chronic Disease; D003167:Complement Activation / Q000276:immunology*; D015936:Complement C5a / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D007073:Immunoglobulin E / Q000494:pharmacology; D008407:Mast Cells / Q000502:physiology; D017455:Receptors, IgE / Q000037:antagonists & inhibitors; D012867:Skin / Q000166:cytology / Q000187:drug effects; D014581:Urticaria / Q000378:metabolism*
D017455:Receptors, IgE; D007073:Immunoglobulin E; D015936:Complement C5a