Purpose

For patients with end stage lung disease, lung transplantation (LT) remains the only definitive treatment option. Long term survival post LT is limited by acute and chronic allograft dysfunction. Antibodies to lung self-antigens Kα1Tubulin and collagen V (autoantibodies) have been implicated in adverse outcomes post LT. The aim of our study was to determine the prevalence of autoantibodies in pre- and post-transplant sera, evaluate the impact on post-transplant outcomes.

Methods

In a prospective observational cohort analysis, 44 patients were enrolled who received LT between 09/01/2014 and 10/31/2015. Pre- and post-transplant sera were analyzed using enzyme-linked immunosorbent assay (ELISA) for the presence of antibodies to collagen I, collagen V, and K-alpha 1 tubulin. The outcome variables are presence of primary graft dysfunction (PGD), cumulative acute cellular rejection (ACR), treatment with pulse steroids for clinical rejection, association with DSA, and onset of Bronchiolitis Obliterans Syndrome (BOS).

Results

In our cohort, 33 patients (75%) tested positive for the presence of autoantibodies. Pre-transplant autoantibodies were present in 23 patients (70%). Only a small percentage (26%) cleared these antibodies with standard immunosuppression. Some developed de novo post-transplant (n = 10). PGD was observed in 34% of our cohort, however the presence of autoantibodies did not correlate with increase in the incidence or severity of PGD. The prevalence of donor specific antibodies (DSA) in the entire cohort was 73%, with an increased prevalence of DSA noted in the autoantibody positive group (78.7% vs. 54.5%) than in the autoantibody negative group. BOS was observed in 20% of the cohort, with a median time to onset of 291 days' post-transplant. Patients with pre-transplant autoantibodies had a statistically significant decrease in BOS-free survival (p = 0.029 by log-rank test).

Conclusions

In our cohort, we observed a high prevalence of autoantibodies and DSA in lung transplant recipients. Pre-transplant autoantibodies were associated with de novo development of DSA along with a decrease in BOS-free survival. Limitations to our study include the small sample size and single center enrollment, along with limited time for follow-up.

中文翻译：

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肺移植受者中肺部自身抗原（Kα1微管蛋白和胶原蛋白V）抗体和HLA供体特异性抗体的流行及其对肺移植结果的影响：单中心经验。

目的

对于患有晚期肺部疾病的患者，肺移植（LT）仍然是唯一的确定性治疗选择。LT后的长期生存受到同种异体移植急性和慢性功能障碍的限制。肺部自身抗原Kα1Tubulin和胶原蛋白V（自身抗体）的抗体与LT后的不良后果有关。我们研究的目的是确定移植前和移植后血清中自身抗体的患病率，评估对移植后结果的影响。

方法

在一项前瞻性观察性队列分析中，纳入了44位在2014年9月1日至2015年10月31日之间接受LT治疗的患者。使用酶联免疫吸附测定（ELISA）分析移植前后的血清中是否存在针对胶原蛋白I，胶原蛋白V和K-alpha 1微管蛋白的抗体。结果变量是原发性移植物功能障碍（PGD），累积急性细胞排斥反应（ACR），用于临床排斥反应的脉冲类固醇治疗，与DSA关联以及闭塞性细支气管炎综合征（BOS）发作的存在。

结果

在我们的队列中，有33名患者（75％）自身抗体检测呈阳性。移植前自身抗体存在于23名患者中（70％）。只有一小部分（26％）用标准免疫抑制清除了这些抗体。一些人进行了从头移植后的新生（n = 10）。在我们的队列中有34％观察到PGD，但是自身抗体的存在与PGD发生率或严重性的增加无关。在整个队列中，供体特异性抗体（DSA）的患病率为73％，与自身抗体阴性组相比，自身抗体阳性组的DSA患病率有所提高（78.7％对54.5％）。在20％的队列中观察到BOS，中位时间为移植后291天。

结论

在我们的队列中，我们观察到肺移植接受者自身抗体和DSA的患病率很高。移植前自身抗体与DSA的重新发展以及无BOS存活率降低有关。我们研究的局限性包括样本量小和单中心入组，以及随访时间有限。