The fate of anti-HLA antibodies following liver transplantation

Abstract

Introduction: Liver transplant recipients may have pre-formed anti-HLA antibodies directed to mismatched HLA of the liver donor (donor specific antibodies, DSA) or not directed to the liver donor (non-donor specific, non-DSA). We observed the fate of these antibodies (DSA and non-DSA) at 12 months after transplant.

Methods: Patients transplanted between 4/2015 and 12/2018 (N = 216) who had anti-HLA antibody measurements at both transplant and 12 months posttransplant (N = 124) and with DSAs at transplant (N = 31) were considered informative for a paired analysis of the natural history of DSA and non-DSA following liver transplantation.

Results: Class I DSAs and non-DSAs decreased between transplant and 12 months; however, Class I DSAs essentially disappeared by 12 months while Class I non-DSAs did not. Anti-HLA Class II DSAs performed differently. While there was a significant drop in values between transplant and 12 months, these antibodies mostly persisted at a low level.

Discussion: Our study demonstrated a significant difference in the kinetics of DSA compared to non-DSA following liver transplantation, most profoundly for anti-HLA Class I antibodies. Class I DSAs were mostly absent at 12 months while Class II DSAs persisted, although at lower levels. The mechanisms of reduction in anti-HLA antibodies following liver transplantation are not completely understood and were not pursued as a part of this study. This detailed analysis of Class I and Class II DSAs and non-DSAs represents and important study to explore the change in antibodies at one year from liver transplantation.

Keywords: HLA class I and class II typing; anti HLA antibodies; donor specific antibodies; liver graft survival; liver transplant.

Figure 1

MFI of DSAs and non-DSAs at transplant and 12 months after transplant. Thirty-one patients had DSAs. The Figure compares seventy-six DSAs and 181 non-DSAs from those patients. Each line represents the value of an individual antibody at transplant and again at 12 months. There was a significant reduction in MFI by 12 months for both DSAs and non-DSAs, although the percent reduction for DSAs was significantly greater than for non-DSAs.

Figure 2

MFI of Class I DSAs and Class I non-DSAs at transplant and 12 months after transplant. Twenty-two patients had Class I DSAs. The Figure compares 39 DSAs and 103 non-DSAs from those patients. Each line represents the value of an individual antibody at transplant and again at 12 months. There was a significant reduction in MFI by 12 months for both DSAs and non-DSAs, although the percent reduction for DSAs was significantly greater than for non-DSAs.

Figure 3

MFI of Class II DSAs and Class II non-DSAs at transplant and 12 months after transplant. Twenty patients had Class II DSAs at transplant. The Figure compares 37 DSAs and 78 non-DSAs from those patients. Each line represents the value of an individual antibody at transplant and again at 12 months. There was a significant reduction in MFI by 12 months for both DSAs and non-DSAs, although the percent reduction for DSAs was not different from that of non-DSAs.

Figure 4

Percent reduction in MFI from transplant to 12 months after transplant. Thirty-one patients had Class I and/or Class II DSAs. The Figure compares 39 Class I DSAs to 37 Class II DSAs from those patients; and, 103 Class I non-DSAs to 78 Class II non-DSAs from those patients. The percent reduction was significantly greater for Class I DSAs compared to Class II DSAs. There was no difference in percent reduction between Class I non-DSAs and Class II non-DSAs.

Figure 5

Graft survival. One-hundred-two patients had anti HLA antibodies at transplant. Thirty-one had Class I and/or Class II DSAs. Seventy-one did not have DSAs at transplant. There was no difference in outcome between these groups.