Contribution of renal secreted complement C3 to the circulating pool in humans.
Complement C3 produced within the kidney may be an important mediator of local inflammatory and immunological injury. The overall level of renal C3 production and consequently its contribution to the total circulating C3 level are, however, unknown. This was investigated by using the conversion of C3 from recipient to donor allotype following renal transplantation. The C3 F and S allotypes of 80 consecutive renal donor-recipient pairs (148 individuals) were determined by amplification refractory mutation system analysis. The extent of allotype conversion in C3 F/S mismatched recipients was quantified at different stages after transplantation, using an enzyme-linked immunosorbent assay specific for the HAV 4-1 polymorphism of C3 that is strongly associated with C3F. Twenty-one of the eighty recipients were potentially informative, i.e., were C3 SS recipients of C3 FF or FS donor kidneys. In the early postoperative period, donor-derived C3 (HAV 4-1-positive) was undetectable, increasing to 9.6% of the total circulating C3 at times of acute allograft rejection. When graft dysfunction occurred from causes other than rejection, donor C3 remained undetectable. After stable graft function was attained (3-13 mo after transplantation), donor C3 made up 4.5% of the total circulating C3 pool. Our findings demonstrate that human transplant kidney in the resting state is a significant source of extrahepatic C3. Its heightened local synthesis during rejection episodes suggests a possible pathogenic role for C3 in this immunological process.
Tang
S
S
Department of Nephrology and Transplantation, Guy's Hospital, London, United Kingdom.
Zhou
W
W
Sheerin
N S
NS
Vaughan
R W
RW
Sacks
S H
SH
D000293:Adolescent; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000097:blood; D015153:Blotting, Western; D002648:Child; D003176:Complement C3 / Q000276:immunology / Q000378:metabolism*; D004252:DNA Mutational Analysis; D005260:Female; D005784:Gene Amplification; D006084:Graft Rejection; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D007674:Kidney Diseases; D016030:Kidney Transplantation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period
D000911:Antibodies, Monoclonal; D003176:Complement C3