Pre-existing self-reactive IgA antibodies associated with primary graft dysfunction after lung transplantation.,Transplant Immunology

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Pre-existing self-reactive IgA antibodies associated with primary graft dysfunction after lung transplantation.
Transplant Immunology ( IF 1.6 ) Pub Date : 2020-01-30 , DOI: 10.1016/j.trim.2020.101271
Vaidehi Kaza ₁ , Chengsong Zhu ₂ , Leying Feng ₂ , Fernando Torres ₁ , Srinivas Bollineni ₁ , Manish Mohanka ₁ , Amit Banga ₁ , John Joerns ₁ , T Mohanakumar ₃ , Lance S Terada ₁ , Quan-Zhen Li ₂

Affiliation

Background

Primary graft Dysfunction (PGD) results in significant mortality and morbidity after lung transplantation (LT). The objective of this study was to evaluate if pre-existing antibodies to self-antigens in sera of LT recipients are associated with PGD.

Methods

The serum profiles of IgG and IgA autoantibodies were analyzed using a customized proteomic microarray bearing 124 autoantigens. Autoantibodies were analyzed using Mann-Whitney U test or Fisher exact test. The association of the autoantibodies with clinical phenotypes and survival was analyzed by Kaplan-Meier Survival Analysis. Receiver operating curve characteristics (ROC) were calculated to evaluate the predictive value of the autoantibodies for PGD.

Results

51 patients were included in this study. Autoantigen microarray analysis on the pre-transplantation samples identified 17 IgA and 3 IgG autoantibodies which were significantly higher in recipients who developed PGD compared to those who did not (adjusted p < .05 and fold change>1.5). 6 IgA Abs were significantly associated with survival. Taken as a panel, an elevation of 6 IgA Abs had significant predictive value for PGD. Area under the curve value for the panel was 0.9413 for PGD with ROC analysis. Notably, 6 of the 17 IgA autoantigen targets are belong to proteoglycan family of extracellular matrix proteins.

Conclusion

Pre-existing IgG and IgA autoantibodies in LT patients correlate with PGD and with survival in a single center, small cohort of lung transplant recipients. Further validation is needed to confirm the findings in the study.

中文翻译：

已有的自我反应性IgA抗体与肺移植后的原发性移植物功能障碍有关。

背景

原发性移植物功能障碍（PGD）导致肺移植（LT）后明显的死亡率和发病率。这项研究的目的是评估LT受体血清中自身抗原的预先存在的抗体是否与PGD相关。

方法

IgG和IgA自身抗体的血清谱使用载有124种自身抗原的定制蛋白质组微阵列进行了分析。使用Mann-Whitney U检验或Fisher精确检验分析自身抗体。自身抗体与临床表型和生存的关联通过Kaplan-Meier生存分析进行了分析。计算受体工作曲线特征（ROC）以评估PGD自身抗体的预测值。

结果

该研究包括51例患者。移植前样品的自身抗原微阵列分析确定了17种IgA和3种IgG自身抗体，与未形成PGD的受试者相比，这些受试者的PGD明显高于未校正的受试者（校正后的p <.05且倍数变化> 1.5）。6 IgA Abs与生存率显着相关。作为一个小组，升高6 IgA Abs对PGD具有重要的预测价值。对于具有ROC分析的PGD，面板的曲线值下的面积为0.9413。值得注意的是，17个IgA自身抗原靶标中有6个属于细胞外基质蛋白的蛋白聚糖家族。