Impact of transplant accessibility for sensitized patients by avoiding unacceptable antigens

Abstract

Recent data have confirmed the negative impact of preformed donor-specific antibodies (pDSAs) after liver transplantation (LT). In order to reduce the risk of developing lesions associated with acute and chronic antibody-mediated rejection in LT recipients, we evaluated the consequences in terms of transplant accessibility, associated with avoiding pDSAs according to several mean fluorescence intensity (MFI) titer thresholds that have been previously reported to be relevant in LT. Among the 484 included LT candidates, 99 (20.5%) presented with anti-human leukocyte antibodies (HLAs). The predictive factors for anti-HLA sensitization were a history of previous kidney transplantation (odds ratio [OR], 1.5; 95% confidence interval [CI], 1.30-1.9; P = 0.05), a history of previous LT (OR, 1.9; 95% CI, 1.6-2.1; P = 0.01), a history of blood transfusion (OR, 2.5; 95% CI, 2.2-4.1; P = 0.01), and a history of pregnancy (OR, 2.9; 95% CI, 2.4-3.3; P = 0.04). By applying a strategy of unacceptable mismatches for recipients with an antibody (Ab) MFI of > 5000, only 35 patients were affected (7% of the cohort), but 22 of these (63%) would have been considered incompatible with >50% of the donors. Using a MFI threshold of >10,000, only 16 patients were affected (1.4% of the cohort), but half of these would have been considered incompatible with >50% of the proposed donors. Considering only those with anti-class II Ab and a MFI >5000 and >10,000, respectively, 10/14 and 4/8 patients were considered incompatible with >50% of the donors. In conclusion, avoiding pDSAs affects a small but not negligible proportion of LT candidates. However, in these sensitive patients, avoiding pDSAs has the potential to significantly reduce the donor pool and, consequently, transplant accessibility. Liver Transplantation 23 880-886 2017 AASLD.

Treatment of Anti-HLA Donor-Specific Antibodies Results in Increased Infectious Complications and Impairs Survival after Liver Transplantation

“…This observation was even more evident in LT recipients with preformed DSA (65.3% women). The result is in accordance with the published data [ 13 , 15 , 32 ] and explained by previous pregnancies as the main trigger for anti-HLA antibodies prior to solid organ transplantation [ 39 , 40 , 41 , 42 ].…”

Outcome of Liver Transplant Patients With Preformed Donor‐Specific Anti–Human Leukocyte Antigen Antibodies

“…The lack of difference in the mortality rates between patients with and without pDSAs in our study confirms that considering accepted or unacceptable HLA antigens for LT is not required. We had previously reported that applying such an allocation strategy would dramatically reduce the accessibility to transplantation for a large proportion of patients …”

“…LT with pDSAs is a common situation because pretransplant sensitizing events (including blood transfusions) are frequent in patients on the waiting list and because the supposed weak detrimental effect of antibody‐mediated immunity leads transplant physicians to not consider the presence of pDSAs with graft acceptance . However, few data concerning the medium‐term and longterm impact of pDSAs exist.…”

Risk factors for antibody-mediated rejection in ABO blood-type incompatible and donor-specific antibody-positive liver transplantation

“…Thirty patients underwent LDLT, while 10 received deceased-donor LT. Preoperative recipient status was at-home (18), hospitalized (20), and intensive care unit-bound (2). The median MELD score was 20 (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29). Sum-MFI of HLA Class-I, -II, and -I + II were 1643 (0-6909), 3871 (0-12,116), and 7124 (3904-17,995), respectively.…”

“…The median age was 55 years (IQR: 43-59). Primary diseases included HCV (28), HBV (19), and primary biliary cholangitis (PBC) (17). Thirty patients were diagnosed with HCC.…”