Predominant role of the Fab fragment in delaying hyperacute rejection in guinea pig-to-rat xenotransplantation.
BACKGROUND
Human intravenous immunoglobulin G delayed xenogeneic hyperacute rejection (HAR) in the guinea pig-to-rat combination. We investigated the respective roles of the Fc and Fab fragments of the IgG molecule in this inhibitory effect.


METHODS
By using a guinea pig-to-rat heart transplantation model, the efficiency of IgG, Fab, and Fc in prolonging the grafted heart's survival time (ST) was compared.


RESULTS
A dose-dependent increase in the ST was observed with Fab (r=0.74, P < 0.0001), IgG (r=0.57, P < 0.001), and Fc (r=0.51, P < 0.01). The linear regression slopes with Fab and with IgG were, respectively, sevenfold and fourfold steeper than with Fc. The ST was significantly longer than controls (23+/-7 min) after infusion of 2 g/kg IgG (147+/-42 min) or 1 g/kg Fab (176+/-38 min), whereas the highest dose of Fc (1.5 g/kg) did not induce significant prolongation of ST. In terms of equivalent functional doses, 1 g/kg Fab was significantly more potent in prolonging the ST than 1.5 g/kg IgG (87+/-25 min) or 0.5 g/kg Fc (33+/-14 min). Analysis of the rejected hearts evidenced edema, necrosis, and rat C3 deposits characteristic of HAR.


CONCLUSIONS
These results indicated that the delaying action of intravenous immunoglobulin G on HAR in the guinea pig-to-rat combination is mostly mediated through the Fab fragment.
Urbani
L
L
Laboratoire de Recherche Chirurgicale, Faculté de Médecine Cochin-Port-Royal, Paris, France.
Fabre
M
M
Cardoso
J
J
Lambin
P
P
Devillier
P
P
Soubrane
O
O
Houssin
D
D
Gautreau
C
C
D000818:Animals; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival / Q000502:physiology; D006168:Guinea Pigs; D016027:Heart Transplantation / Q000276:immunology*; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007140:Immunoglobulin Fab Fragments / Q000502:physiology*; D007141:Immunoglobulin Fc Fragments / Q000502:physiology; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D014183:Transplantation, Heterologous / Q000276:immunology*; D016042:Transplantation, Heterotopic / Q000276:immunology
D007140:Immunoglobulin Fab Fragments; D007141:Immunoglobulin Fc Fragments