Figure 2
Figure 2. IV.3, AT-10, and MDE-8 mAbs induce Fc-mediated hypothermia and thrombocytopenia. (A) Core body temperature changes in FCGR2A mice after IV injection of recombinant effector-competent (native) or effector-deficient chimeric IV.3 mAb. (B) CBT changes of mice injected with recombinant chimeric AT-10 in IgG1 (native) or IgG1 E269R (effector-deficient), or with mouse AT-10 (included for comparison). (C) Core body temperature changes following injection of native or effector-deficient MDE-8 mAbs. (D) Whole-blood platelet counts from FCGR2A mice following injection of different quantities (1 animal per dose) of native cIV.3 IgG2 or effector-deficient cIV.3 IgG2 N297A. (E) Bar chart showing the percentage of platelets remaining in circulation following IV injection of native and effector-deficient CD32a antibodies. The 3 antibody types marked with the # symbol were combined (50 µg each or 100 µg each) for high-dose combination injections, as designated. Unless otherwise noted (# symbol and panel D), each animal was injected with 70 to 140 µg of mAb. It should be noted that, due to insufficient yield, effector-deficient recombinant IV.3 (IgG1 E269R), as well as chimeric AT-10 (cAT-10) IgG2 and cAT-10 IgG2 N297A mAbs could not be extensively evaluated in FCGR2A mice.

IV.3, AT-10, and MDE-8 mAbs induce Fc-mediated hypothermia and thrombocytopenia. (A) Core body temperature changes in FCGR2A mice after IV injection of recombinant effector-competent (native) or effector-deficient chimeric IV.3 mAb. (B) CBT changes of mice injected with recombinant chimeric AT-10 in IgG1 (native) or IgG1 E269R (effector-deficient), or with mouse AT-10 (included for comparison). (C) Core body temperature changes following injection of native or effector-deficient MDE-8 mAbs. (D) Whole-blood platelet counts from FCGR2A mice following injection of different quantities (1 animal per dose) of native cIV.3 IgG2 or effector-deficient cIV.3 IgG2 N297A. (E) Bar chart showing the percentage of platelets remaining in circulation following IV injection of native and effector-deficient CD32a antibodies. The 3 antibody types marked with the # symbol were combined (50 µg each or 100 µg each) for high-dose combination injections, as designated. Unless otherwise noted (# symbol and panel D), each animal was injected with 70 to 140 µg of mAb. It should be noted that, due to insufficient yield, effector-deficient recombinant IV.3 (IgG1 E269R), as well as chimeric AT-10 (cAT-10) IgG2 and cAT-10 IgG2 N297A mAbs could not be extensively evaluated in FCGR2A mice.

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