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. 2020 May;20(5):1365-1374.
doi: 10.1111/ajt.15766. Epub 2020 Jan 18.

Reassessment of the clinical impact of preformed donor-specific anti-HLA-Cw antibodies in kidney transplantation

Jonathan Visentin  1   2   3 , Thomas Bachelet  4   5 , Olivier Aubert  6 , Arnaud Del Bello  7   8 , Charlie Martinez  4 , Frédéric Jambon  2   3   4 , Gwendaline Guidicelli  1 , Mamy Ralazamahaleo  1 , Charlène Bouthemy  1 , Marine Cargou  1 , Nicolas Congy-Jolivet  8   9   10 , Thoa Nong  11 , Jar-How Lee  11 , Rebecca Sberro-Soussan  12   13 , Lionel Couzi  2   3   4 , Nassim Kamar  7   8   14 , Christophe Legendre  12   13 , Pierre Merville  2   3   4 , Jean-Luc Taupin  1   2   3
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Free article

Reassessment of the clinical impact of preformed donor-specific anti-HLA-Cw antibodies in kidney transplantation

Jonathan Visentin et al. Am J Transplant. 2020 May.
Free article

Abstract

Anti-denatured HLA-Cw antibodies are highly prevalent, whereas anti-native HLA-Cw antibodies seem to lead to random flow cytometry crossmatch results. We aimed to reassess crossmatch prediction for anti-HLA-Cw using 2 types of single antigen flow beads (classical beads and beads with diminished expression of denatured HLA), and to compare the pathogenicity of preformed anti-denatured and anti-native HLA-Cw antibodies in kidney transplantation. We performed 135 crossmatches with sera reacting against donor HLA-Cw (classical beads fluorescence ≥500); only 20.6% were positive. Forty-three (31.6%) were anti-denatured HLA antibodies (beads with diminished expression of denatured HLA fluorescence <300); all were crossmatch negative. The correlation between classical beads fluorescence and the crossmatch ratio was low (ρ = 0.178), and slightly higher with beads with diminished expression of denatured HLA (ρ = 0.289). We studied 52 kidney recipients with preformed anti-HLA-Cw donor-specific antibodies. Those with anti-native HLA antibodies experienced more acute and chronic antibody-mediated rejections (P = .006 and .03, respectively), and displayed a lower graft survival (P = .04). Patients with anti-native HLA-Cw antibodies more frequently had previous sensitizing events (P < .000001) or plausibility of their antibody profile according to known anti-native HLA-Cw eplets (P = .0001). Anti-native but not anti-denatured HLA-Cw antibodies are deleterious, which underscores the need for reagents with diminished expression of denatured HLA.

Keywords: alloantibody; basic (laboratory) research/science; clinical research/practice; crossmatch; flow cytometry; histocompatibility; kidney transplantation/nephrology; major histocompatibility complex (MHC); rejection: antibody-mediated (ABMR).

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