Human leukocyte antigens antibodies after lung transplantation: Primary results of the HALT study

Abstract

Donor-specific antibodies (DSA) to mismatched human leukocyte antigens (HLA) are associated with worse outcomes after lung transplantation. To determine the incidence and characteristics of DSA early after lung transplantation, we conducted a prospective multicenter observational study that used standardized treatment and testing protocols. Among 119 transplant recipients, 43 (36%) developed DSA: 6 (14%) developed DSA only to class I HLA, 23 (53%) developed DSA only to class II HLA, and 14 (33%) developed DSA to both class I and class II HLA. The median DSA mean fluorescence intensity (MFI) was 3197. We identified a significant association between the Lung Allocation Score and the development of DSA (HR = 1.02, 95% CI: 1.001-1.03, P = .047) and a significant association between DSA with an MFI ≥ 3000 and acute cellular rejection (ACR) grade ≥ A2 (HR = 2.11, 95% CI: 1.04-4.27, P = .039). However, we did not detect an association between DSA and survival. We conclude that DSA occur frequently early after lung transplantation, and most target class II HLA. DSA with an MFI ≥ 3000 have a significant association with ACR. Extended follow-up is necessary to determine the impact of DSA on other important outcomes.

Keywords: clinical research/practice; histocompatibility; lung transplantation/pulmonology; major histocompatibility complex (MHC); monitoring: immune; rejection: T cell mediated (TCMR); rejection: antibody-mediated (ABMR).

Figure 1

Flow diagram: study screening and eligibility. IVIG: intravenous immune globulin. CMV-IG: cytomegalovirus immune globulin.

Figure 2

Kaplan-Meier freedom from post-transplant donor-specific HLA antibodies (DSA) during the study period. Thin dashed lines depict upper and lower bounds of 95% confidence interval.

Figure 3

A. The proportion of patients who developed post-transplant donor-specific HLA antibodies (DSA) stratified by the number of DSA specificities. B. The proportion of patients who developed post-transplant DSA stratified by DSA specificity. C. Post-transplant DSA mean fluorescence intensity (MFI) stratified by HLA locus. Boxes extend from the 25^th to the 75^th percentiles, whiskers extend to the largest and smallest values within 1.5 times box lengths, and the line within the boxes represents the median. Solid circles represent outlier cases between 1.5 and 3 box lengths from the upper edge of the boxes.