Development of an antibody specific to major histocompatibility antigens detectable by flow cytometry after lung transplant is associated with bronchiolitis obliterans syndrome
Development of an antibody specific to major histocompatibility antigens detectable by flow cytometry after lung transplant is associated with bronchiolitis obliterans syndrome
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DOI：
10.1097/00007890-200209270-00011
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发表时间：
2002-09-27
期刊：
影响因子：
6.2
通讯作者：
Reinsmoen, NL
中科院分区：
文献类型：
--
作者：
Palmer, SM;Davis, RD;Reinsmoen, NL
背景。慢性同种异体移植排斥反应表现为闭塞性细支气管炎综合征（BOS），是肺移植术后晚期死亡的主要原因。尽管越来越多的证据表明抗人类白细胞抗原（HLA）抗体与肾脏或心脏同种异体移植的慢性排斥反应之间存在关联，但抗HLA抗体在肺受体中的临床意义尚不清楚，特别是在先前“致敏”的受体中。使用基于流式细胞术的面板反应性抗体（flow- pra）提供了一种高度敏感的方法来识别肺受体中新生抗hla抗体的发展。Flow-PRA检测用于分析存活至少6个月的稳定无BOS肺受者移植前后血清。移植前流式pra阴性定义的无既往致敏的患者在移植后通过流式pra分析抗hla抗体的存在。采用比例风险模型确定抗hla抗体对BOS风险的影响。在移植后的不同时间点，对90名杜克大学移植前血流- pra阴性受体的血清进行血流- pra检测。11%（10/90）的受者血清中含有可通过流式pra检测到的抗hia抗体。9名患者（90%）产生针对供体抗原的抗hla抗体，1名患者产生针对供体抗原的抗hla 11类抗体。在9例有供体抗原特异性抗体的患者中，flow-PRA特异性分析显示8例对11类抗原有特异性，1例对I类抗原有特异性。在控制其他BOS危险因素的多变量模型中，移植后血流- pra阳性与BOS 1、2或3级（风险比[HR] 3.19； 95%可信区间[CI]: 1.41-7.12， P=0.005）和BOS 2或3级（风险比4.08;95% Cl: 1.66-10.04， P= 0.002）显著相关。4例新生抗hla抗体患者随访期间死亡；四个都是110S。在BOS患者中，hla抗体的存在与生存率显著降低相关（P=0.05， log-rank检验）。虽然不常见，但先前未致敏的肺移植受者可以产生针对供体H类抗原的抗hla抗体。新发抗hla抗体显著增加BOS的风险，与其他移植后事件无关。此外，新生抗hla抗体可识别生存期明显较差的BOS患者。需要进一步的研究来确定ii类定向抗hla抗体是否在肺受体慢性排斥过程中起机制作用。
Background. Chronic allograft rejection manifested as bronchiolitis obliterans syndrome (BOS) is the leading cause of late death after lung transplantation. Although increasing evidence suggests an association between anti-human leukocyte antigens (HLA) antibodies and chronic rejection of kidney or heart allografts, the clinical significance of anti-HLA antibodies in lung recipients is less clear, especially in previously "sensitized recipients. The use of flow cytometry based panel reactive antibody (flow-PRA) provides a highly sensitive means to identify the development of de novo anti-HLA antibodies in lung recipients.Methods. Flow-PRA testing was used to analyze the pre- and posttransplant sera in stable BOS free lung recipients who survived at least 6 months. Patients without prior sensitization as defined by a negative pretransplant flow-PRA were analyzed posttransplant for the presence of anti-HLA antibodies by flow-PRA. A proportional hazards model was used to determine the impact of anti-HLA antibody on BOS risk.Results. Sera from 90 recipients at Duke University with negative pretransplant flow-PRA were tested by flow-PRA at various time points after transplant. Sera from 11% (10/90) of recipients were found to contain anti-HIA antibodies detectable by flow-PRA. Nine patients (90%) developed anti-HLA antibodies specific for donor antigens, and one patient developed anti-HLA class 11 antibodies, not specific to donor antigens. Among the nine patients with donor antigen specific antibodies, flow-PRA specificity analysis demonstrated eight were specific for class 11 antigens and one for class I antigens. In a multivariate model that controls for other BOS risk factors, a positive posttransplant flow-PRA was significantly associated with BOS grades 1,2, or 3 (hazard ratios [HR] 3.19; 95% confidence interval [CI]: 1.41-7.12, P=0.005) and BOS grade 2 or 3 (HR 4.08; 95% Cl: 1.66-10.04, P =0.002). Four patients with de novo anti-HLA antibodies died during follow-up; all four had 110S. Among BOS patients, the presence of anti-HLA antibodies was associated with a significantly worse survival (P=0.05, log-rank test).Conclusions. Although uncommon, previously -unsensitized lung transplant recipients can develop anti-HLA antibodies to donor class H antigens. The development of de novo anti-HLA antibodies significantly increases the risk for BOS, independent of other posttransplant events. Furthermore, de novo anti-HLA antibodies identify BOS patients with significantly worse survival. Additional studies are needed to determine if class II-directed anti-HLA antibodies contribute mechanistically to the chronic rejection process in lung recipients.