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. 2011 Feb;22(2):367-76.
doi: 10.1681/ASN.2010050513. Epub 2010 Dec 16.

Genotypic diversity of complement component C4 does not predict kidney transplant outcome

Markus Wahrmann  1 , Bernd Döhler, Andrea Ruhenstroth, Helmuth Haslacher, Thomas Perkmann, Markus Exner, Andrew J Rees, Georg A Böhmig
Affiliations

Genotypic diversity of complement component C4 does not predict kidney transplant outcome

Markus Wahrmann et al. J Am Soc Nephrol. 2011 Feb.

Abstract

Gene copy number of complement component C4, which varies among individuals, may determine the intrinsic strength of the classical complement pathway. Presuming a major role of complement as an effector in transplant rejection, we hypothesized that C4 genetic diversity may partially explain the variation in allograft outcomes. This retrospective study included 1969 deceased-donor kidney transplants randomly selected from the Collaborative Transplant Study DNA bank. We determined recipient and donor gene copy number of total C4, C4 isotypes (C4A and C4B), and C4 gene length variants (C4L and C4S) by quantitative real-time PCR analysis. Groups defined according to recipient C4 gene copy number (low, intermediate, and high) had similar 10-year allograft survival. Genotypic groups showed comparable rates of graft dysfunction, treatment for rejection, immunological graft loss, hospitalization for infection, malignant disease, and death. Similarly, separate analyses of C4A, C4B, C4L, and C4S; combined evaluation of donor and recipient C4 genotype; or analysis of recipients with higher risk for rejection did not reveal considerable outcome effects. In conclusion, we did not demonstrate that C4 gene copy number associates with transplant outcome, and we found no evidence that the resulting variation in the strength of classical complement activation influences susceptibility to rejection.

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Figures

Figure 1.
Figure 1.
Recipient C4 gene copy number does not associate with kidney allograft survival rates. Rates of graft survival (A), death-censored graft survival (B), and patient survival (C) are shown according to recipient C4 gene copy number group.
Figure 2.
Figure 2.
Recipient C4 gene CNV does not influence the relative distribution of five major categories of graft loss: graft failure for unclear reason (Unclear); failure from immunological rejection (Immunol); nonimmunological failure (Non-Immunol; technical failure included); recurrence of original disease (Rec Dis); and death with functioning graft (Death). The results obtained for the three recipient C4 genotypic groups are shown for the first year (A) and years 2 to 10 (B). Comparisons of groups for individual causes of graft loss did not reveal statistical significance.
Figure 3.
Figure 3.
Recipient C4 gene copy number does not associate with renal allograft function at 1 year.
Figure 4.
Figure 4.
Recipient and donor C4 gene copy number do not associate with survival rates. The rates of overall graft survival (A), death-censored graft survival (B), and patient survival (C) are shown according to recipient-donor genotypic group.
Figure 5.
Figure 5.
C4 gene copy number in presensitized recipients does not associate with renal allograft survival.
See this image and copyright information in PMC

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