Background

Chronic Lung Allograft Dysfunction (CLAD) remains the major limitation in long term survival after lung transplantation. Our objective is to evaluate for the presence of autoantibodies to self-antigens, which is a pathway along with complex interplay with immune as well as non-immune mechanisms that leads to a fibroproliferative process resulting in CLAD.

Methods

Serum profiles of IgG autoantibodies were evaluated using customized proteomic microarray with 124 antigens. Output from microarray analyzed as antibody scores is correlated with bronchiolitis obliterans (BOS) subtype of CLAD using Mann-Whitney U test or Fisher exact test. Autoantibodies were evaluated for their predictive value for progressive BOS using a Cox proportional hazard model. BOS free survival and overall survival was analyzed using Kaplan-Meier survival analysis.

Results

Forty- two patients included in the study are grouped into “stable BOS” and “progressive BOS” for comparisons. Pulmonary fibrosis is the major indication for lung transplantation in our cohort. Progressive BOS group had significantly worse survival (p < 0.005). Sixteen IgG autoantibodies are significantly elevated at baseline in progressive BOS group. Six among them correlated with worse BOS free survival (p < 0.05). In addition, these six IgG autoantibodies remain elevated at three months and one year after lung transplantation.

Conclusion

Pre-existing IgG autoantibodies correlate with progressive BOS and survival in a single center, small cohort of lung transplant recipients. Further validation with larger sample size, external cohort and confirmation with additional tissue, bronchoalveolar lavage samples are necessary to confirm the preliminary findings in our study.

中文翻译：

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与闭塞性细支气管炎综合征亚型慢性同种异体移植物功能障碍相关的自身反应性抗体

背景

慢性同种异体肺移植物功能障碍 (CLAD) 仍然是肺移植后长期存活的主要限制因素。我们的目标是评估针对自身抗原的自身抗体的存在，这是一种途径以及与免疫和非免疫机制的复杂相互作用，导致纤维增殖过程导致 CLAD。

方法

使用具有 124 种抗原的定制蛋白质组微阵列评估 IgG 自身抗体的血清谱。分析为抗体评分的微阵列输出与使用 Mann-Whitney U检验或 Fisher 精确检验的 CLAD 的闭塞性细支气管炎 (BOS) 亚型相关。使用 Cox 比例风险模型评估自身抗体对进行性 BOS 的预测价值。使用 Kaplan-Meier 生存分析分析无 BOS 生存和总生存。

结果

研究中包括的 42 名患者被分为“稳定 BOS”和“进行性 BOS”进行比较。在我们的队列中，肺纤维化是肺移植的主要适应症。进行性 BOS 组的生存率显着降低 (p < 0.005)。在进行性 BOS 组中，16 种 IgG 自身抗体在基线时显着升高。其中六个与更差的无 BOS 生存相关（p < 0.05）。此外，这六种 IgG 自身抗体在肺移植后三个月和一年时仍然升高。

结论

预先存在的 IgG 自身抗体与进行性 BOS 和在单个中心、小群肺移植受者中的存活相关。需要用更大的样本量、外部队列进行进一步验证，并用额外的组织、支气管肺泡灌洗液样本进行确认，以确认我们研究中的初步发现。