Acute Humoral Rejection in the Absence of Anti-HLA Antibodies, a French Nation-Wide Study.

Antibody mediated rejection (ABMR) is usually associated with donor-specific anti-HLA antibodies (DSA). Evidence of ABMR in patients with no DSA strongly suggests the implication of non-HLA antibodies. We implemented a retrospective nation-wide study to improve undertanding of non-HLA ABMR. Inclusion criteria were: first or re-transplantion, deceased or living-donor; acute allograft dysfunction during the first three months; allograft biopsy showing a total score of glomerulitis and peritubular capillaritis≥3 according to the Banff classification; absence of identified anti-HLA DSAs using Luminex®. Demographical and clinical parameters were collected for 36 cases. Recipient age was 53±19 yrs. Donor age was 53±12 yrs. Cold ischemia time was 12±8 hrs. All patients received induction therapy (94% basiliximab, 6% thymoglobuline), a CNI (69% tacrolimus, 31% cyclosporine), MPA and steroids. Rejection was diagnosed at day 12±9 in the absence of graft function recovery in 30% of patients. The remaining 25 patients defined a poor serum creatinine nadir of 289±169 μmol/L at day 15±22. Acute graft dysfunction (393±230 μmol/L) led to the diagnosis of acute rejection at day 25±34. No anti-HLA DSA were observed. Mean g+ptc score was 3,8 [3-6]. In addition, intimal arteritis and interstitial inflammation (i ≥1) were observed in 50% and 69% of cases, respectively. Additional lesions included haemorragic suffusion and thrombotic microangiopathy in 26% and 9% of cases, respectively. Therapeutic strategies included steroids pulses (86%), thymoglobulines (37%), rituximab (31%), IVIG (49%) and plasmapheresis (49%). Primary non function was observed in 2 cases. At last follow up (3±1 yrs) serum creatinine was 178±92 μmol/l. 6% of patients were back to dialysis. This study provides a close clinico-pathological description of non-HLA ABMR, and will be followed by additional histological and mechannistic analyses.