Complement-binding anti-HLA DSA have demonstrated higher rejection rate and decreased allograft outcome. We investigated the effect of terminal complement inhibition (Eculizumab) in a cohort of patients with C1q-binding DSA at the time of transplantation.

We enrolled 2 groups of patients, all with C1q-binding DSA at the time of transplantation between 2011 and 2013: i) 12 patients (study group) received Eculizumab in the prevention of AMR according to a phase 2 clinical trial (NCT01567085); ii) A matched control group of 12 patients receiving standard of care (PP x4 and IVIG 2g/kg BW). Surveillance kidney allograft biopsies were performed at 14 days and 12 months post-transplant in all patients. In both groups the allograft injury phenotype was assessed by histopathology and gene expression. DSA characteristics, GFR and proteinuria were also determined at those time points.

Baseline characteristics were similar in both groups in term of donor, recipient, transplant and DSA characteristics. At Day-14, patients receiving Eculizumab had lower histological Banff scores for peritubular capillaritis (p=0.0074), interstitial inflammation (p=0.0133) and tubulitis (p=0.0055). Molecular allograft gene expression revealed lower AMR activity reflected by decreased endothelial DSA-selective transcripts (DSAST, 3.97 fold-change, p<0.001) and ABMR Molecular Score (1.81 fold-change p=0.0061). This lower activity was related to lower expression of NK transcripts (NKb, 5.25 fold-change, p<0.0001), macrophage transcripts (QCMAT, 1.67 fold-change, p=0.04), IFNG production and inducing transcripts (GRIT, 2.65 fold-change, p<0.001) and acute kidney injury transcripts (IRRATS, 1.53 fold-change, p=0.01) as compared with patients receiving standard of care. At 1-year (after 9 months of treatment wash out), the histologic scores (g, ptc, cg, C4d, i, t, v, IFTA and cv) and molecular scores for ABMR, GRIT, QCMAT and IRRATS were similar in both groups with the exception of NKb (1.8 fold-change, p=0.02) and DSAST (2 fold-change, p=0.01). At 1 year, eGFR and DSAmax MFI were similar in both groups while there was a trend lo lower proteinuria among the Eculizumab treated group (p=0.0562).

Eculizumab prophylaxis in patients with C1q-binding DSA reduces early AMR activity with major effect on NK burden with limited effect after treatment discontinuation.

CITATION INFORMATION: Lefaucheur C, Hidalgo L, Reeve J, Viglietti D, Gosset C, Aubert O, Ulloa C, Legendre C, Glotz D, Halloran P, Loupy A. Effect of Complement Inhibition Therapy (Eculizumab) in Patients with C1q-Binding Donor-Specific Anti-HLA Antibodies: A Molecular Appraisal. Am J Transplant. 2016;16 (suppl 3).

« Back to 2016 American Transplant Congress