Food, drug, insect sting allergy, and anaphylaxisRapid desensitization of mice with anti-FcγRIIb/FcγRIII mAb safely prevents IgG-mediated anaphylaxis
Section snippets
Mice
Female BALB/c and C57BL/6 mice were purchased from Taconic (Hudson, NY) and were used at 7 to 12 weeks of age. FcγRIII-deficient and FcγRI-deficient mice on a BALB/c background1, 18 were a gift of Dr Jeffrey Ravetch (Rockefeller University, New York, NY); these mice were bred to each other to generate mice deficient in both FcγRI and FcγRIII. F2 offspring were typed by PCR to identify double-deficient offspring. FcγRIIb-deficient mice on a C57BL/6 background were purchased from the Jackson
Rapid desensitization with anti-FcγRII/RIII mAb (2.4G2) avoids direct toxicity and prevents IgG-mediated anaphylaxis
To determine whether a rapid desensitization approach could prevent the development of anaphylaxis in mice injected with 2.4G2, we first determined the dose of 2.4G2 required to induce shock (hypothermia) in BALB/c mice (Fig 1, A). A significant and substantial decrease in temperature was observed in mice injected with 63 μg or more of this mAb but not in mice injected with 31 μg. In contrast, serial, hourly injections of mice with doubling doses of 2.4G2, starting with a dose of 15 μg and
Discussion
The results of our studies indicate that rapid desensitization with an IgG mAb specific for FcγRIIb and FcγRIII safely allows complete inhibition of IgG-mediated anaphylaxis. Although shock is induced in mice given a single injection of 63 μg of 2.4G2, mice injected hourly with doubling doses of that mAb, starting with a dose of 15 μg, failed to anaphylax in response to 500 μg of 2.4G2, even if pretreated with a long-acting formulation of IL-4 that considerably increases sensitivity to this mAb.
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Supported by the US Department of Veterans Affairs Merit Award (F.D.F.).
Disclosure of potential conflict of interest: M. Khodoun, D. Krishnamurthy, and F. Finkelman have a provisional patent, and there is potential that money may be paid to them and their institution. Z. Kucuk has received a grant from the National Institutes of Health. The rest of the authors declare that they have no relevant conflicts of interest.
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These authors contributed equally to this work.
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Durga Krishnamurthy is currently affiliated with the Department of Pathophysiology and Allergy Research, Center of Pathophysiology, Infectiology and Immunology, Medical University of Vienna, Vienna, Austria.