Cutaneous anaphylaxis in mice to Der p 2 independent of IgE and IgG1

Rationale We have recently shown that immunoglobulin free light chains (IgLC) can elicit immediate hypersensitivity-like responses (Nature Medicine 8, 694, 2002). In this study, we investigated if cutaneous anaphylaxis to a major house dust mite (HDM) antigen could be induced by IgLC. Methods Mice were intradermally sensitized with two Der p 2-specific IgLC to different epitopes. At twenty hours mice received an intravenous challenge with HDM extract or recDer p 2 and changes in ear thickness were monitored. To investigate if anaphylaxis could be inhibited by a specific IgLC antagonist, F991, mice were injected i.p. with 50 microgram F991 at the time of sensitization. Results Intracutaneous injection of 2C5 and A4 followed by intravenous challenge with recDer p or HDM extract resulted in a rapid development of ear swelling reaching a maximum at 10 to 30 min after challenge. At 60 min post challenge, the ear thickness returned to basal levels. The PCA induced by crosslinking of Der p 2-specific Ig light chains could be completely prevented by F991. Conclusions The role of IgE in atopic dermatitis (AD) induced by aeroallergens remains controversial. Total or Ag-specific IgE does not always correlate with clinical symptoms. In several studies a discordance between the results from the atopy patch test or skin prick test and the levels of IgE specific for HDM were reported. We show that Der p 2-specific IgLC can elicit an IgE/IgG1-independent cutaneous anaphylaxis. Our study suggests that induction of immediate hypersensitivity-like responses via IgLC might be responsible for positive skin reactions in non-atopic or intrinsic AD.