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肺移植患者的外周 B 细胞亚群比例与健康对照者不同。

Lung Transplant Patients Show a Dissimilar Peripheral B-Cell Subset Ratio Compared With Healthy Controls.

机构信息

>From the Interstitial Lung Diseases, Centre of Excellence, Department of Pulmonology, St. Antonius Hospital, Nieuwegein, The Netherlands.

出版信息

Exp Clin Transplant. 2020 Apr;18(2):234-241. doi: 10.6002/ect.2019.0240.

DOI:10.6002/ect.2019.0240
PMID:32279657
Abstract

OBJECTIVES

Lung transplant is a last treatment option for patients with end-stage pulmonary disease. Chronic lung allograft dysfunction, which generally manifests as bronchiolitis obliterans syndrome, is a major long-term survival limitation. Bronchiolitis obliterans syndrome is diagnosed when forced expiratory volume in 1 second declines > 20% in the absence of known causes. B cells can either contribute or restrain the development of bronchiolitis obliterans syndrome (eg, via induction of alloimmune antibodies, regulation of cellular immunity, and induction of tolerance). Here, we explored how peripheral B-cell subsets were altered in lung transplant recipients with bronchiolitis obliterans syndrome.

MATERIALS AND METHODS

Fresh whole blood samples were analyzed from 42 lung transplant recipients, including 17 with bronchiolitis obliterans syndrome; samples from these groups were compared with 10 age-matched healthy control samples. B-cell subsets were analyzed using flow cytometry, and relative distributions of subsets were compared. Changes in forced expiratory volume in 1 second were also determined.

RESULTS

Absolute B-cell count was significantly increased in transplant recipients with bronchiolitis obliterans syndrome. Transitional (CD24+CD38+) and naïve (CD27-IgD+) B cells were decreased in lung transplant patients, with transitional B cells almost absent in those with bronchiolitis obliterans syndrome. Double-negative (CD27-IgD-) memory B cells were significantly increased (P < .001). No differences were found for plasmablasts (CD38+CD24-) and switched (CD27+IgD-) and non-switched (CD27+IgD+) memory B cells. Correlation analyses showed positive correlations between lung function and naïve B cells in transplant recipients (P = .0245; r = -0.458).

CONCLUSIONS

Peripheral B-cell count and subset distribution were altered in lung transplant recipients with and without bronchiolitis obliterans syndrome compared with healthy controls. Transitional and naïve B-cell decreases may be caused by differentiation toward double-negative B-cells, which were increased. The correlation between forced expiratory volume and naïve B cells during follow-up care may be clinically interesting to investigate.

摘要

目的

肺移植是终末期肺部疾病患者的最后治疗选择。慢性肺移植物功能障碍,通常表现为闭塞性细支气管炎综合征,是长期生存的主要限制。当 1 秒用力呼气量下降超过 20%且无已知原因时,即可诊断为闭塞性细支气管炎综合征。B 细胞可以促进或抑制闭塞性细支气管炎综合征的发展(例如,通过诱导同种免疫抗体、调节细胞免疫和诱导耐受)。在这里,我们探讨了在患有闭塞性细支气管炎综合征的肺移植受者中,外周 B 细胞亚群是如何改变的。

材料和方法

分析了 42 例肺移植受者的新鲜全血样本,包括 17 例闭塞性细支气管炎综合征患者;将这些组的样本与 10 例年龄匹配的健康对照组样本进行比较。使用流式细胞术分析 B 细胞亚群,并比较各亚群的相对分布。还确定了 1 秒用力呼气量的变化。

结果

患有闭塞性细支气管炎综合征的移植受者的 B 细胞绝对计数显著增加。肺移植患者的过渡(CD24+CD38+)和幼稚(CD27-IgD+)B 细胞减少,而过渡 B 细胞在闭塞性细支气管炎综合征患者中几乎不存在。双阴性(CD27-IgD-)记忆 B 细胞显著增加(P <.001)。浆母细胞(CD38+CD24-)和已转换(CD27+IgD+)和未转换(CD27+IgD+)记忆 B 细胞无差异。相关性分析显示,移植受者的肺功能与幼稚 B 细胞呈正相关(P =.0245;r = -0.458)。

结论

与健康对照组相比,患有和不患有闭塞性细支气管炎综合征的肺移植受者的外周 B 细胞计数和亚群分布发生改变。幼稚 B 细胞和过渡 B 细胞的减少可能是向双阴性 B 细胞分化所致,而双阴性 B 细胞增加。在随访过程中,用力呼气量与幼稚 B 细胞之间的相关性可能具有临床意义,值得进一步研究。

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