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.
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.
Authors: Marco Delsante; Umberto Maggiore; Jonathan Levi; David E Kleiner; Annette M Jackson; Lois J Arend; Stephen M Hewitt; Naima Carter-Monroe; Serena M Bagnasco; Avi Z Rosenberg Journal: Transpl Int Date: 2018-12-11 Impact factor: 3.782
Authors: Jean Kwun; Marie Matignon; Miriam Manook; Soulef Guendouz; Vincent Audard; David Kheav; Elsa Poullot; Chantal Gautreau; Brian Ezekian; Diane Bodez; Thibault Damy; Laureline Faivre; Dehbia Menouch; Janghoon Yoon; Jaeberm Park; Karim Belhadj; Dongfeng Chen; Alyssa M Bilewski; John S Yi; Bradley Collins; Mark Stegall; Alton B Farris; Stuart Knechtle; Philippe Grimbert Journal: J Am Soc Nephrol Date: 2019-06-21 Impact factor: 10.121
Authors: Sandy Feng; John C Bucuvalas; Anthony J Demetris; Bryna E Burrell; Katherine M Spain; Sai Kanaparthi; John C Magee; David Ikle; Andrew Lesniak; Juan J Lozano; Estella M Alonso; Robert A Bray; Nancy E Bridges; Edward Doo; Howard M Gebel; Nitika A Gupta; Ryan W Himes; Annette M Jackson; Steven J Lobritto; George V Mazariegos; Vicky L Ng; Elizabeth B Rand; Averell H Sherker; Shikha Sundaram; Yumirle P Turmelle; Alberto Sanchez-Fueyo Journal: Gastroenterology Date: 2018-08-23 Impact factor: 22.682