Chronic Lung Allograft Dysfunction is Associated with an Increased Number of Non-HLA Antibodies,The Journal of Heart and Lung Transplantation

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Chronic Lung Allograft Dysfunction is Associated with an Increased Number of Non-HLA Antibodies
The Journal of Heart and Lung Transplantation ( IF 8.9 ) Pub Date : 2023-12-21 , DOI: 10.1016/j.healun.2023.12.007
Qingyong Xu , Mohamed Elrefaei , Jean-Luc Taupin , Kelley MK Hitchman , Steven Hiho , Alison Gareau , Carlo Iasella , Marilyn Marrari , Natalia Belousova , Maria Bettinotti , Tathagat Narula , Francisco Alvarez , Pablo G. Sanchez , Bronwyn Levvey , Glen Westall , Gregory Snell , Deborah J. Levine , Adriana Zeevi , Antoine Roux

Background

Chronic Lung Allograft Dysfunction (CLAD) is the major cause of adverse outcomes in lung transplant recipients. Multiple factors, such as infection, alloimmunity, and autoimmunity, may lead to CLAD. Here, we aim to examine the role of non-HLA antibodies in CLAD in a large retrospective cohort.

Methods

We analyzed non-HLA antibodies in the pre-and post-transplant sera of 226 (100 CLAD, 126 stable) lung transplant recipients from 5 centers, and we used a separate cohort to confirm our findings.

Results

A panel of 18 non-HLA antibodies was selected for analysis based on their significantly higher positive rates in CLAD vs. stable groups. The panel-18 non-HLA antibodies (n>3) may be positive pre- or post-transplant; the risk for CLAD is higher in the latter. The presence of both non-HLA antibody and HLA donor-specific antibody (DSA) was associated with an augmented risk of CLAD (HR=25.09 [5.52–14.04], p <0.001), which was higher than that for single-positive patients. In the independent confirmatory cohort of 61 (20 CLAD, 41 stable) lung transplant recipients, the risk for CLAD remained elevated in double-positive patients (HR=10.67 [0.98–115.68], p=0.052). After adjusting for non-standard immunosuppression, patients with double-positive DSA/Non-HLA antibodies had an elevated risk for graft loss (HR=2.53 [1.29–4.96], p=0.007).

Conclusions

Circulating non-HLA antibodies (n>3) were independently associated with a higher risk for CLAD. Furthermore, when non-HLA antibodies and DSA were detected concomitantly, the risk for CLAD and graft loss was significantly increased. These results show that humoral immunity to HLA and non-HLA antigens may contribute to CLAD development.

中文翻译：

慢性肺同种异体移植功能障碍与非 HLA 抗体数量增加相关

背景

慢性同种异体肺移植功能障碍（CLAD）是肺移植受者不良结果的主要原因。感染、同种免疫和自身免疫等多种因素可能导致 CLAD。在这里，我们旨在通过大型回顾性队列研究非 HLA 抗体在 CLAD 中的作用。

方法

我们分析了来自 5 个中心的 226 名（100 名 CLAD，126 名稳定）肺移植受者的移植前和移植后血清中的非 HLA 抗体，并使用单独的队列来证实我们的研究结果。

结果

选择一组 18 种非 HLA 抗体进行分析，是因为它们在 CLAD 组中的阳性率明显高于稳定组。第 18 组非 HLA 抗体 (n>3) 可能在移植前或移植后呈阳性；后者发生 CLAD 的风险更高。非 HLA 抗体和 HLA 供体特异性抗体 (DSA) 的存在与 CLAD 风险增加相关（HR=25.09 [5.52–14.04]，p <0.001），高于单阳性患者。在由 61 名（20 名 CLAD，41 名稳定）肺移植受者组成的独立验证队列中，双阳性患者的 CLAD 风险仍然较高（HR=10.67 [0.98–115.68]，p = 0.052）。在调整非标准免疫抑制后，DSA/非 HLA 双阳性患者的移植物丢失风险升高（HR=2.53 [1.29–4.96]，p =0.007）。