The 2017 Banff meeting has focused on the importance of a precise diagnosis of IF/TA in kidney recipients by addressing specific etiological factors. Recent studies showed a significant contribution of alloimmune factors (both T cell- and antibody-mediated process) to the development of IF/TA. This study investigated the role of anti-HLA DSAs and their characteristics in the progression of IF/TA.

We prospectively included 1004 kidney recipients transplanted between 2004 and 2010, with systematic assessment of injury phenotype and IF/TA Banff score on allograft biopsies performed at 1 year after transplantation. All patients were assessed for DSAs and their characteristics (HLA class, de novo status, MFI, C1q binding) at 6 months post-transplant. Patients were followed up to 8 years and we integrated all for cause biopsies performed beyond 1 year (N=539) to assess IF/TA progression.

We identified 416 (41%) patients with IF/TA0 score, 278 (28%) patients with IF/TA1 score, 165 (16%) patients with IF/TA2 score and 145 (15%) patients with IF/TA3 score. The prevalence of DSAs increased with IF/TA severity: 79/416 (19%) in IF/TA0 patients, 67/278 (24%) in IF/TA1 patients, 47/165 (28%) in IF/TA2 patients and 52/145 (36%) in IF/TA3 patients. DSA MFI was positively correlated with IF/TA severity (rho=0.21, p=0.001), with MFI of 3543±3167 in IF/TA0 patients, 4093±4779 in IF/TA1 patients, 5071±5391 in IF/TA2 patients and 7816±6222 in IF/TA3 patients. C1q-binding DSA prevalence also increased with IF/TA severity: 14/416 (3%) in IF/TA0 patients, 13/278 (5%) in IF/TA1 patients, 17/165 (10%) in IF/TA2 patients and 24/145 (17%) in IF/TA3 patients (p<0.001). Among all DSA characteristics, C1q binding was the most important one to predict the severity of IF/TA in random forest analysis (mean decrease in accuracy: 22%). Patients with C1q-binding DSA had a higher IF/TA score at 1 year post-transplant compared to patients with non-C1q-binding DSA (1.8±1.2 vs. 1.1±1.1, p<0.001), increased microvascular inflammation (p<0.001) and C4d deposition in peritubular capillaries (p<0.001), and they exhibited accelerated progression of IF/TA (p=0.02) beyond 1 year post-transplant.

C1q-binding anti-HLA DSAs are associated with premature and accelerated kidney allograft fibrosis, with a biological gradient between DSA C1q-binding ability and fibrosis severity, suggesting a causal effect of DSA in an alloimmune subtype of fibrosis.

CITATION INFORMATION: Louis K., Viglietti D., Aubert O., Loupy A., Lefaucheur C. Role of C1q-Binding Donor-Specific Anti-HLA Antibodies in Premature and Accelerated Kidney Allograft Interstitial Fibrosis Am J Transplant. 2017;17 (suppl 3).

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