Immunomodulation in experimental and clinical nephrology using chimeric proteins.
The objective of immunosuppressive therapy in nephrology is to prevent autoimmune diseases and to suppress kidney allograft rejections while sparing other effects. Increased clarification of the underlying immune mechanism has made specific immunodulation possible using chimeric proteins in which the variable domains of an immunoglobulin are replaced by extracellular domains of cell surface molecules or cytokines. The immunosuppressive effects of fusion proteins such as CTLA-4 IgG, CD40 IgG, interleukin (IL)-10 IgG, IL-2 IgG or tumor necrosis factor (TNF)-receptor IgG have been proven in various animal models. Moreover, the application of TNF-receptor IgG successfully limited the OKT3-induced cytokine release syndrome in kidney graft recipients. It seems likely that recombinant proteins with increasingly effective suppression of specific elements of the immune response will become an essential element in clinical protocols.
Kunzendorf
U
U
Department of Internal Medicine and Nephrology, Universitätsklinikum Benjamin Franklin, Berlin, Germany.
Pohl
T
T
Bulfone-Paus
S
S
Krause
H
H
Ziegler
E
E
Onu
A
A
Distler
A
A
D000069594:Abatacept; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000627:therapeutic use; D019013:CD40 Antigens / Q000627:therapeutic use; D060908:CTLA-4 Antigen; D016207:Cytokines / Q000627:therapeutic use; D015433:Glomerulonephritis, Membranous / Q000517:prevention & control; D006084:Graft Rejection / Q000276:immunology / Q000517:prevention & control*; D006801:Humans; D018796:Immunoconjugates; D007074:Immunoglobulin G / Q000627:therapeutic use; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D016030:Kidney Transplantation / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000627:therapeutic use*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D019013:CD40 Antigens; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D016207:Cytokines; D018796:Immunoconjugates; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D000069594:Abatacept