Purpose: While complement activation via both the classical as well as the lectin pathway is believed to contribute to allograft loss, their relative contribution is unknown. Here we used an allogeneic heart transplant (Tx) model in rats to test if inhibition of the lectin pathway delays graft rejection.

Methods: Donor hearts from Brown Norway rats were heterotopically transplanted into the abdomen of Lewis rats treated with either vehicle or a monoclonal antibody (mAb) directed against the lectin pathway-specific serine protease MASP-2 (n=6 rats/treatment group). Treatments were administered twice weekly by intravenous injection. The primary endpoint was graft survival as determined by echocardiography. Allografts were harvested for histopathological analyses on day of rejection, and in additional transplanted animals four days after Tx.

Results: MASP-2 mAb treatment was well tolerated in all animals (good general conditions, relative increase in weight 1.02±0.05 versus 0.97±0.06 in control group, p=0.132). Compared with controls, transplant recipients treated with MASP-2 mAb experienced a delayed graft rejection (graft survival 8±2 days versus 13±6 days; mean±SD; p=0.026). After been rejected, grafts in the MASP-2 mAb-treated group experienced less increase in graft weight compared to controls (84±47% versus 161±72% relative to pre transplantation plate; p=0.041). Harvested beating grafts on day four showed histological signs for cellular rejection in both groups. Autopsy of the graft survival groups negate relevant macroscopic alterations in antiMASP-2 Ab treated animals.

Conclusion and Outlook: Inhibition of lectin-dependent complement activation via blockade of MASP-2 resulted in improved cardiac graft survival. Immunohistopathologic analyses in accordance to the ISHLT grading will clarify if the benefit of antiMASP-2 Ab treatment is based on delayed cardiac antibody-mediated rejection.

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