Relationships between antibodies against human soluble complement receptor 1 (hsCR1) from various species

Abstract

The relationships between antibodies against human soluble complement receptor 1 (hsCR1) were studied in rodents, dogs, nonhuman primates, and humans. An antibody response occurred in all species except humans. The anti-hsCR1 antibodies from the various species were characterized to determine if they recognize similar epitopes on the hsCR1 molecule. Dog and monkey sera, positve for hsCR1 binding, were used as blocking antibodies against mouse anti-hsCR1 monoclonal antibodies as well as mouse and rat anti-hsCR1-positive sera. Human sera (blood group antisera: anti-Knops, anti-McCoy, anti-Knops/McCoy, anti-Swain-Langley) and serum from one burn patient (who became seropositive despite ever receiving treatment with hsCR1) were also used to test blocking of mouse, rat, dog, and monkey anti-hsCR1. Characterization of anti-hsCR1 antibodies from different species demonstrated that hsCR1 causes divergent antibody responses among animals. While mouse, rat, and dog antibodies cross inhibit binding by approximately 50%, monkey antibodies recognize primarily different epitopes of the hsCR1 molecule. Moreover, human antibodies binding hsCR1 are completely different from the animal antibodies, including monkey. This study indicates that although hsCR1 is immunogenic in animals, there is a difference in response between species, particularly between nonprimates and primates, and finally, that this antibody response is not predictive for humans.

The complement system in hypertension and renal damage in the Dahl SS rat

“…A limitation of using human sCR1 in rodent models is that only short‐term treatment is possible because of the inevitable development of an immune response to the molecule (Ruggieri et al. ). The dose used in this study was based on a variety of early studies using 10–20 mg/kg of this molecule to inhibit complement activation in the rat or pig (Piddlesden et al.…”

“…It is a recombinant human molecule that has been demonstrated to be effective in inhibiting complement activation in the rat, mouse, and guinea pig (Regal et al 1993;Lillegard et al 2013). A limitation of using human sCR1 in rodent models is that only short-term treatment is possible because of the inevitable development of an immune response to the molecule (Ruggieri et al 1996). The dose used in this study was based on a variety of early studies using 10-20 mg/kg of this molecule to inhibit complement activation in the rat or pig (Piddlesden et al 1994(Piddlesden et al , 1996Goodfellow et al 1997;Chai et al 2000), as well as our more recent study in the pregnant rat where the hypertension induced by reduced placental perfusion was significantly attenuated by daily administration of 15 mg/kg sCR1 (Lillegard et al 2013) over a 4-5 day time period.…”

A review of pig liver xenotransplantation: Current problems and recent progress

“…Primate complement‐mediated pig liver injury has been prevented or reduced by the introduction into the pig of transgenes for human complement‐regulatory proteins, for example, hCD46 (MCP), hCD55 (DAF), and/or hCD59 . Alternatively, expression in the pig of soluble complement‐receptor‐1 (sCR‐1) has been proposed and tested …”