Effects of complement inactivation and IgG depletion on skin reactivity to autologous serum in chronic idiopathic urticaria.
BACKGROUND
Intradermal injection of autologous serum elicits a wheal-and-flare response in about 60% of patients with chronic idiopathic urticaria (CIU). This reactivity has been attributed to the presence of IgG autoantibodies directed against IgE or the alpha-chain of the high-affinity IgE receptor (FcepsilonRIalpha) expressed on basophils and mast cells, leading to the hypothesis that at least some forms of CIU could be sustained by an autoimmune process.


OBJECTIVE
The aim of this study was to investigate the relationship between the presence of anti-IgE or anti-FcepsilonRI antibodies and the ability to induce wheal-and-flare responses in CIU sera selected for the capacity to give a positive skin test response.


METHODS
Fifteen patients with CIU and a positive skin test response to autologous serum were injected intradermally with native serum and with serum heated at 56 degrees C for 30 minutes and then adsorbed on Sepharose-protein G to obtain IgG depletion. Serum levels of anti-IgE and anti-FcepsilonRIalpha antibodies were measured by ELISA by using purified IgE and recombinant RIalpha-soluble double-fusion protein RIalpha-human serum albumin-RIalpha, respectively. The histamine-releasing activity of sera was tested by using ELISA with whole human blood from a healthy donor.


RESULTS
All patients had positive cutaneous responses to native serum injection. Anti-FcepsilonRIalpha antibodies were present in 14 of 15 native sera, only two of which were able to induce in vitro basophil degranulation. On the contrary, detectable amounts of anti-IgE antibodies were not found in any serum. IgG depletion by protein G resulted in complete (10/14 samples) or considerable (4/14 samples) removal of anti-FcepsilonRIalpha antibodies. The two sera endowed with functional activity lost their capacity to trigger histamine release from basophils after heating and protein G adsorption. Nonetheless, heat-decomplemented/IgG-depleted sera elicited wheal-and-flare reactions comparable with those observed with untreated sera.


CONCLUSIONS
These results strongly suggest that skin reactivity to autologous serum could be due to as yet unidentified non-Ig reactants present in the sera of patients with CIU.
Fagiolo
U
U
Department of Medical and Surgical Sciences, Padova, Austria.
Kricek
F
F
Ruf
C
C
Peserico
A
A
Amadori
A
A
Cancian
M
M
D000328:Adult; D000906:Antibodies / Q000097:blood; D000888:Antibodies, Anti-Idiotypic / Q000097:blood / Q000276:immunology; D001323:Autoantibodies / Q000097:blood; D002908:Chronic Disease; D003169:Complement Inactivator Proteins / Q000494:pharmacology*; D005260:Female; D006632:Histamine / Q000097:blood; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D017455:Receptors, IgE / Q000276:immunology; D012867:Skin / Q000276:immunology*; D012882:Skin Tests; D014581:Urticaria / Q000097:blood* / Q000209:etiology
D000906:Antibodies; D000888:Antibodies, Anti-Idiotypic; D001323:Autoantibodies; D003169:Complement Inactivator Proteins; D007074:Immunoglobulin G; D017455:Receptors, IgE; C026408:anti-IgE antibodies; D006632:Histamine