Inhibition of C3 with pegcetacoplan results in normalization of hemolysis markers in paroxysmal nocturnal hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematologic disorder characterized by complement-mediated hemolysis. C5 inhibitors (eculizumab/ravulizumab) control intravascular hemolysis but do not prevent residual extravascular hemolysis. The newly approved complement inhibitor, pegcetacoplan, inhibits C3, upstream of C5, and has the potential to improve control of complement-mediated hemolysis.

Complement C3 Inhibitor Pegcetacoplan for Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Randomized Phase 2 Trial.

Purpose: Geographic atrophy (GA), a late stage of age-related macular degeneration (AMD), is a major cause of blindness. Even while central visual acuity remains relatively well preserved, GA often causes considerable compromise of visual function and quality of life. No treatment currently exists.

Neuroregeneration in composite tissue allografts: effect of low-dose FK506 and mycophenolate mofetil immunotherapy.

Background: The immunosuppressant FK506 has been reported to increase the rate of peripheral nerve regeneration in nerve crush injury and nerve allograft models. The purpose of this study was to determine whether low doses of FK506 and mycophenolate mofetil had a neuroregenerative effect in revascularized peripheral nerve allografts in a rat hind limb transplantation model.

Methods: Wistar Furth rat recipients received limbs from syngeneic Wistar Furth donors (group 1, n = 4) or from allogeneic August X Copenhagen Irish rat donors (group 2, n = 6).

Vascularized lymph node transplantation induces graft-versus-host disease in chimeric hosts.

Background: The role of lymph nodes (LNs) in adaptive immune responses has been the subject of extensive research. In previous studies, the surgical removal of lymph nodes from rat hind limbs prevented the development of lethal graft-versus-host disease (GVHD) after allogeneic hind limb transplantation to chimeric recipient rats. The purpose of this study was to establish the role of the cellular fraction versus the microenvironment of LNs in the development of GVHD in this model.

Risk acceptance in composite-tissue allotransplantation reconstructive procedures.

Composite-tissue allotransplantation (CTA) is a new therapeutic modality to reconstruct major tissue defects of the face, larynx, and extremities. Unlike most life-saving organ-transplantation procedures, CTA is considered to improve quality of life. Therefore, the question arises, do the risks posed by the immunosuppression drugs that patients must take to prevent rejection justify the benefits of these procedures? The purpose of this study was to assess the relative risk that individuals are willing to accept in order to receive the benefits of CTA procedures.

Lymphadenectomy prior to rat hind limb allotransplantation prevents graft-versus-host disease in chimeric hosts.

In previous rat studies, the use of mixed allogeneic chimerism (MAC) to induce host tolerance to hind limb allografts has resulted in severe graft-versus-host disease (GVHD). The purpose of this study was to determine if immunocompetent cells in bone marrow (BM) and/or lymph nodes (LNs) of transplanted limbs were responsible for inducing GVHD in mixed chimeric hosts. [ACI-->Wistar Furth] chimeric rats received ACI hind limbs that were non-irradiated, irradiated (1050 cGy) or lymphadenectomized.

Composite tissue allotransplantation in chimeric hosts part II. A clinically relevant protocol to induce tolerance in a rat model.

Background: We and others have shown that mixed allogeneic chimerism induces donor-specific tolerance to composite tissue allografts across major histocompatibility complex barriers without the need for immunosuppression. However, a delay period between bone marrow transplantation and limb allotransplantation is required, making such protocols impractical for clinical application. This study eliminates this delay period in a rat hind limb allotransplantation model by performing mixed allogeneic chimerism induction and transplantation "simultaneously.

Low-dose immunosuppression in a rat hind-limb transplantation model.

Composite tissue allografts (CTAs) offer an alternative to conventional reconstructive methods. However, the toxicity of the drugs that are required to prevent rejection has prevented its widespread clinical application. The purpose of this study was to determine whether a low-dose, corticosteroid-free combination regimen of tacrolimus and mycophenolate mofetil (MMF) would prevent rejection in a rat hind-limb model, with minimal toxic side effects.

Composite tissue allotransplantation in chimeric hosts: part I. Prevention of graft-versus-host disease.

Background: Mixed allogeneic chimerism (MAC) has been shown to induce tolerance to composite tissue allografts (CTA). However, transplantation of unmanipulated donor-specific limbs results in severe graft-versus-host disease (GVHD). This suggests that nontolerant mature donor-derived cells in the CTA may affect the stability of chimerism, potentially resulting in GVHD.