SUMMARYComplement activation in 73 renal transplant biopsies was investigated by indirect immunoperoxidasc staining using MoAbs rcacEivc with complement-splil products. Intense deposition of complement fragments C4d and C3d in pcritubulur capillaries, indicating activation of the classical pathway, eould be detected in the majority of transplanted kidneys wilh cell-mediated rejections. Abundant deposition of complement-split products was observed in 22 early biop.sies from patients with high 'immunological risk* (i.e. previous, rejected transplants and/or circulating antibodies against HLA-antigens). Despite negative results in the crossmatch before transplantation and paueity of immunoglobulins in transplant biopsies, antibodies directed against endothelial eell antigens should be eonsidered as a possible cause of elassical complement activation.
The novel severe acute respiratory syndrome (SARS)-like coronavirus (SARS-CoV-2) enters its host cells after binding to the angiotensin-converting enzyme 2 (ACE2) via its spike glycoprotein. This interaction is critical for virus entry and virus-host membrane fusion. Soluble ACE2 ectodomains bind and neutralize the virus but the short in vivo half-lives of soluble ACE2 limits its therapeutic use. Fusion of the fragment crystallizable (Fc) part of human immunoglobulin G (IgG) to the ACE2 ectodomain can prolong the in vivo half-life but bears the risk of unwanted Fc-receptor activation and antibody-dependent disease enhancement. Here, we describe optimized ACE2-Fc fusion constructs that avoid Fc-receptor binding by using IgG4-Fc as a fusion partner. The engineered ACE2-IgG4-Fc fusion proteins described herein exhibit promising pharmaceutical properties and a broad antiviral activity at single-digit nanomolar concentration. In addition, they allow to maintain the beneficial enzymatic activity of ACE2 and thus are very promising candidate antivirals broadly acting against coronaviruses.
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