BACKGROUND: Recent studies indicate that not all low-level donor-specific human leukocyte antigen (HLA) antibodies (HLA-DSA) (i.e., positive by solid-phase assays, negative by complement-dependent cytotoxic-crossmatch) have a detrimental clinical impact. The aim of this study was to investigate whether the pretransplant C4d-fixing capability allows distinguishing harmful from presumably clinically irrelevant HLA-DSA. METHODS: We retrospectively investigated 64 patients with low-level HLA-DSA detected by single-antigen flow beads (SAFB). Thirty-four of 64 patients (53%) experienced early antibody-mediated rejection (AMR), whereas 30 patients (47%) did not. HLA-DSA characteristics (i.e., number, class, and strength), frequency of retransplants, and immunosuppressive regimens were not different in these two groups. Pretransplant sera were reanalyzed using a modified SAFB assay measuring C4d fixation induced by HLA antibodies. RESULTS: C4d-fixing HLA-DSA were observed in 11 of 64 patients (17%). AMR occurred in 6 of 11 patients (55%) with C4d-fixing HLA-DSA and in 28 of 53 patients (53%) without C4d-fixing HLA-DSA (P=1.0). Positive C4d staining in peritubular capillaries was detected in 6 of 11 patients (55%) with C4d-fixing HLA-DSA and in 21 of 53 patients (40%) without C4d-fixing HLA-DSA (P=0.50). CONCLUSION: The pretransplant capability of low-level HLA-DSA to trigger C4d fixation in vitro is not predictive for early AMR or C4d deposition in peritubular capillaries in vivo. This argues against pretransplant C4d SAFB testing to define the clinical relevance of low-level HLA-DSA.
BACKGROUND: Recent studies indicate that not all low-level donor-specific human leukocyte antigen (HLA) antibodies (HLA-DSA) (i.e., positive by solid-phase assays, negative by complement-dependent cytotoxic-crossmatch) have a detrimental clinical impact. The aim of this study was to investigate whether the pretransplant C4d-fixing capability allows distinguishing harmful from presumably clinically irrelevant HLA-DSA. METHODS: We retrospectively investigated 64 patients with low-level HLA-DSA detected by single-antigen flow beads (SAFB). Thirty-four of 64 patients (53%) experienced early antibody-mediated rejection (AMR), whereas 30 patients (47%) did not. HLA-DSA characteristics (i.e., number, class, and strength), frequency of retransplants, and immunosuppressive regimens were not different in these two groups. Pretransplant sera were reanalyzed using a modified SAFB assay measuring C4d fixation induced by HLA antibodies. RESULTS: C4d-fixing HLA-DSA were observed in 11 of 64 patients (17%). AMR occurred in 6 of 11 patients (55%) with C4d-fixing HLA-DSA and in 28 of 53 patients (53%) without C4d-fixing HLA-DSA (P=1.0). Positive C4d staining in peritubular capillaries was detected in 6 of 11 patients (55%) with C4d-fixing HLA-DSA and in 21 of 53 patients (40%) without C4d-fixing HLA-DSA (P=0.50). CONCLUSION: The pretransplant capability of low-level HLA-DSA to trigger C4d fixation in vitro is not predictive for early AMR or C4d deposition in peritubular capillaries in vivo. This argues against pretransplant C4d SAFB testing to define the clinical relevance of low-level HLA-DSA.
Authors: G N de Graav; M Dieterich; D A Hesselink; K Boer; M C Clahsen-van Groningen; R Kraaijeveld; N H R Litjens; R Bouamar; J Vanderlocht; M Tilanus; I Houba; A Boonstra; D L Roelen; F H J Claas; M G H Betjes; W Weimar; C C Baan Journal: Clin Exp Immunol Date: 2015-05 Impact factor: 4.330
Authors: Marianne Delville; Baptiste Lamarthée; Sylvain Pagie; Sarah B See; Marion Rabant; Carole Burger; Philippe Gatault; Magali Giral; Olivier Thaunat; Nadia Arzouk; Alexandre Hertig; Marc Hazzan; Marie Matignon; Christophe Mariat; Sophie Caillard; Nassim Kamar; Johnny Sayegh; Pierre-François Westeel; Cyril Garrouste; Marc Ladrière; Vincent Vuiblet; Joseph Rivalan; Pierre Merville; Dominique Bertrand; Alain Le Moine; Jean-Paul Duong Van Huyen; Anne Cesbron; Nicolas Cagnard; Olivier Alibeu; Simon C Satchell; Christophe Legendre; Emmanuel Zorn; Jean-Luc Taupin; Béatrice Charreau; Dany Anglicheau Journal: J Am Soc Nephrol Date: 2019-03-08 Impact factor: 10.121