Complement-binding anti-HLA antibodies and kidney-allograft survival.
BACKGROUND
Anti-HLA antibodies hamper successful transplantation, and activation of the complement cascade is involved in antibody-mediated rejection. We investigated whether the complement-binding capacity of anti-HLA antibodies plays a role in kidney-allograft failure.


METHODS
We enrolled patients who received kidney allografts at two transplantation centers in Paris between January 1, 2005, and January 1, 2011, in a population-based study. Patients were screened for the presence of circulating donor-specific anti-HLA antibodies and their complement-binding capacity. Graft injury phenotype and the time to kidney-allograft loss were assessed.


RESULTS
The primary analysis included 1016 patients. Patients with complement-binding donor-specific anti-HLA antibodies after transplantation had the lowest 5-year rate of graft survival (54%), as compared with patients with non-complement-binding donor-specific anti-HLA antibodies (93%) and patients without donor-specific anti-HLA antibodies (94%) (P<0.001 for both comparisons). The presence of complement-binding donor-specific anti-HLA antibodies after transplantation was associated with a risk of graft loss that was more than quadrupled (hazard ratio, 4.78; 95% confidence interval [CI], 2.69 to 8.49) when adjusted for clinical, functional, histologic, and immunologic factors. These antibodies were also associated with an increased rate of antibody-mediated rejection, a more severe graft injury phenotype with more extensive microvascular inflammation, and increased deposition of complement fraction C4d within graft capillaries. Adding complement-binding donor-specific anti-HLA antibodies to a traditional risk model improved the stratification of patients at risk for graft failure (continuous net reclassification improvement, 0.75; 95% CI, 0.54 to 0.97).


CONCLUSIONS
Assessment of the complement-binding capacity of donor-specific anti-HLA antibodies appears to be useful in identifying patients at high risk for kidney-allograft loss.
Paris Translational Research Center for Organ Transplantation, INSERM Unité 970, Department of Kidney Transplantation, Hôpital Necker, Université Paris Descartes, and Assistance Publique-Hôpitaux de Paris (AP-HP), Paris, France. alexandreloupy@gmail.com
Alexandre
A
Loupy
Carmen
C
Lefaucheur
Dewi
D
Vernerey
Christof
C
Prugger
Jean-Paul
JP
Duong van Huyen
Nuala
N
Mooney
Caroline
C
Suberbielle
Véronique
V
Frémeaux-Bacchi
Arnaud
A
Méjean
François
F
Desgrandchamps
Dany
D
Anglicheau
Dominique
D
Nochy
Dominique
D
Charron
Jean-Philippe
JP
Empana
Michel
M
Delahousse
Christophe
C
Legendre
Denis
D
Glotz
Gary S
GS
Hill
Adriana
A
Zeevi
Xavier
X
Jouven
D000328:Adult; D000906:Antibodies / Q000378:metabolism*; D003165:Complement System Proteins / Q000378:metabolism*; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006801:Humans; D053208:Kaplan-Meier Estimate; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011485:Protein Binding / Q000502:physiology; D014184:Transplantation, Homologous
D000906:Antibodies; D006680:HLA Antigens; D003165:Complement System Proteins