De novodonor-specific anti-HLA antibodies mediated rejection in liver-transplant patients

Abstract

Summary The incidence and consequences of de novo donor‐specific anti‐HLA antibodies (DSAs) after liver transplantation (LT) are not well known. We investigated the incidence, risk factors, and complications associated with de novo DSAs in this setting. A total of 152 de novo liver‐transplant patients, without preformed anti‐HLA DSAs, were tested for anti‐HLA antibodies, with single‐antigen bead technology, before, at transplantation, at 1, 3, 6 and 12 months after transplantation, and thereafter annually and at each time they presented with increased liver‐enzyme levels until the last follow‐up, that is, 34 (1.5–77) months. Twenty‐one patients (14%) developed de novo DSAs. Of these, five patients had C1q‐binding DSAs (24%). Younger age, low exposure to calcineurin inhibitors, and noncompliance were predictive factors for de novo DSA formation. Nine of the 21 patients (43%) with de novo DSAs experienced an acute antibody‐mediated rejection (AMR). Positive C4d staining was more frequently observed in liver biopsies of patients with AMR (9/9 vs. 1/12, P < 0.0001). Eight patients received a B‐cell targeting therapy, and one patient received polyclonal antibodies. Only one patient required retransplantation. Patient‐ and graft‐survival rates did not differ between patients with and without DSAs. In conclusion, liver‐transplant patients with liver abnormalities should be screened for DSAs and AMR.

Prevalence, Risk Factors, and Impact of Donor‐Specific Alloantibodies After Adult Liver Transplantation

“…Antibodies were mostly directed against anti–class II antigens (anti‐DQ locus for 85%) . In the French cross‐sectional study reported by Del Bello et al, 14% of 152 patients developed de novo DSAs (with an MFI ≥ 1000) with a median (range) follow‐up of 34 (1.5‐77) months, directed against anti–class II antigens for 86% . In another article, the same authors report that 13.1% of 267 patients had at least 1 DSA (with an MFI ≥ 1000) at a median (range) of 51 (6‐220) months after transplantation, and that the incidence of de novo DSAs was variable according to the time since transplantation (0% for 6‐12 months, 10% for 1‐3 years, 5% for 3‐5 years, and 11.2% for >5 years) …”

The Role of Humoral Alloreactivity in Liver Transplantation: Lessons Learned and New Perspectives

“…Although up to 25% of LT candidates may be sensitized heading into transplantation, the vast majority of LT recipients clear all preformed DSA by four months after transplant [11]. The incidence of de novo DSA is approximately 5–14% after LT [13, 15, 18, 19], whereas de novo DSA has been reported in up to 28% of recipients following kidney transplantation [35]. The reasons for the apparently lower incidence of de novo DSA in LT have yet to be completely elucidated but may be attributable to the same mechanisms which confer tolerogenic properties to the liver, including the ability to absorb or neutralize alloantibodies [10, 36], as well as the immunomodulatory milieu imparted by nonparenchymal liver cells, including sinusoidal endothelial cells, Kupffer cells, resident dendritic cells, and hepatic stellate cells [8].…”

New insights into immune mechanisms of antiperlecan/LG3 antibody production: Importance of T cells and innate B1 cells

“…[1][2][3][4][5][6] Mounting evidence suggests that autoreactive antibodies also contribute to rejection and can have an adverse impact on graft outcome in kidney, heart, and lung transplant patients. [1][2][3][4][5][6] Mounting evidence suggests that autoreactive antibodies also contribute to rejection and can have an adverse impact on graft outcome in kidney, heart, and lung transplant patients.…”