HLA-DQ7 De Novo Donor-Specific Antibodies Are Associated with Increased Risk of Chronic Lung Allograft Dysfunction After Lung Transplantation

TL;DR

This study shows that HLA-DQ7 antibodies after lung transplants are linked to a higher risk of long-term lung failure and rejection-related deaths.

Contribution

The study identifies HLA-DQ7 as a specific antibody type strongly associated with chronic lung allograft dysfunction.

Findings

dnDSA occurred in 25.8% of lung transplant recipients, with class II being most common.

HLA-DQ dnDSA, especially DQ7, were strongly linked to chronic lung allograft dysfunction.

dnDSA-positive patients had higher rejection-attributed mortality compared to dnDSA-negative patients.

Abstract

Background/Objectives: Chronic lung allograft dysfunction (CLAD) remains the leading cause of late graft failure after lung transplantation (LuTX). De novo donor-specific anti-HLA antibodies (dnDSA), especially HLA-DQ, have been implicated; we assessed associations between dnDSA (class and specificity) and CLAD after LuTX. Methods: We retrospectively analyzed all LuTX recipients transplanted from 2005–2018 at a single center (n = 585). dnDSA were measured by Luminex single-antigen bead assays (MFI > 1000) at 1, 3, 6, and 12 months and at least annually thereafter. CLAD was defined by ISHLT criteria; time-to-event comparisons used log-rank testing. Results: dnDSA developed in 151/585 recipients (25.8%), predominantly class II (129/585; 22.1%); class I dnDSA occurred in 52/585 (8.9%). CLAD occurred more frequently in dnDSA-positive than dnDSA-negative recipients (64/151; 42.4% vs. 109/434; 25.1%; p < 0.0001). Rejection-attributed death was higher in dnDSA-positive recipients (19/151; 11.3% vs. 25/434; 5.3%; p = 0.01). Both class I and class II dnDSA were associated with higher CLAD rates (log-rank p < 0.001 each). Locus-specific analyses identified HLA-DQ dnDSA as strongly associated with CLAD (p < 0.0001); DQ7 was the most frequent specificity (n = 44) and showed the strongest association (p < 0.0001). Conclusions: dnDSA after LuTX were associated with increased CLAD incidence and rejection-attributed mortality, with a prominent association for HLA-DQ—particularly DQ7.

Figures