Kaza Vaidehi, Zhu Chengsong, Terada Lance S, Wang Li, Torres Fernando, Bollineni Srinivas, Mohanka Manish, Banga Amit, Joerns John, Mohanakumar T, Li Quan-Zhen
Division of Pulmonary Critical Care, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Department of Immunology, Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Hum Immunol. 2021 Jan;82(1):25-35. doi: 10.1016/j.humimm.2020.10.006. Epub 2020 Oct 28.
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.
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.
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.
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.
慢性肺移植功能障碍（CLAD）仍然是肺移植后长期生存的主要限制因素。我们的目标是评估自身抗原自身抗体的存在情况，这是一条与免疫和非免疫机制复杂相互作用的途径，会导致纤维增生过程，进而引发CLAD。
使用包含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。将微阵列分析得出的抗体评分输出结果，通过曼-惠特尼U检验或费舍尔精确检验，与CLAD的闭塞性细支气管炎（BOS）亚型相关联。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。采用Kaplan-Meier生存分析来分析无BOS生存期和总生存期。
本研究纳入的42例患者被分为“稳定BOS”组和“进行性BOS”组进行比较。肺纤维化是我们队列中肺移植的主要指征。进行性BOS组的生存期明显更差（p<0.005）。进行性BOS组有16种IgG自身抗体在基线时显著升高。其中6种与更差的无BOS生存期相关（p<0.05）。此外，这6种IgG自身抗体在肺移植后3个月和1年时仍保持升高。
在一个单中心、小队列的肺移植受者中，预先存在的IgG自身抗体与进行性BOS和生存期相关。需要更大样本量、外部队列进行进一步验证，并通过额外的组织、支气管肺泡灌洗样本进行确认，以证实我们研究中的初步发现。
