Background

The role of CD19+CD24^highCD38^high B-regulatory cells in solid-organ Transplant (Tx) in acceptance are still scarce. In previous studies on kidney transplant recipients may suggest a protective role of this cell subtype in graft tolerance and the existence of a cross talk between B-and T-regulatory clones. In lung transplantation, the role of B-regulatory cells has never been investigated. In a murine tracheal transplantation model, this subset seems able to prevent tracheal obliteration when in combination with rapamycin. Aim of this study is to analyze peripheral CD19+CD24^highCD38^high B-reg cells counts in a cohort of lung recipients, their association with several clinical and pharmacological variables and their possible association with T regulatory cell.

Methods

From Jan 2009 to Dec 2014, 117 lung Tx recipients were submitted to an immunological follow up I-FU(median: 108.7 months (6.7–310.5)). Immunological follow up consisted of a complete blood peripheral immuno-phenotype, inclusive of CD19+CD24^highCD38^high B-cells (globally 1106 determinations). We tested the association between B-reg and relevant variables by linear or regression models for repeated measures, adjusting for time from Tx.

Results

Among all variables analyzed at multivariate analysis: chronic rejection (OR − 0.19, p = .039), use of Mycophenolate (OR − 0.38, p < .001) and the presence of a concomitant pulmonary infection of S. aureus (OR 0.66, p = .002) and A. fumigatus (OR 0.50, p = .009) were significantly associated to B-reg cell.

No significant correlation between CD19+CD24^highCD38^high B-reg cells and T-reg cells counts was found in our cohort.

Conclusions

Our present data highlight, for the first time, that this cell subset might participate in long-term lung graft acceptance mechanisms.

中文翻译：

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肺移植受者周围的CD19 + CD24highCD38high B调节细胞。

背景

CD19 + CD24^高CD38^高B调节细胞在实体器官移植（Tx）接受中的作用仍然很少。在先前关于肾脏移植的研究中，受体可能暗示了这种细胞亚型在移植耐受中的保护作用，以及B和T调节克隆之间存在交叉干扰。在肺移植中，从未研究过B调节细胞的作用。在鼠气管移植模型中，与雷帕霉素联合使用时，该亚群似乎能够预防气管闭塞。这项研究的目的是分析外周CD19 + CD24^高CD38^高 B-reg细胞在一组肺受体中计数，它们与几种临床和药理学变量有关，并且与T调节细胞可能有关。

方法

从2009年1月至2014年12月，有117位肺Tx受体接受了免疫随访I-FU（中位数：108.7个月（6.7-310.5））。免疫学随访包括完整的外周血免疫表型，包括CD19 + CD24^高CD38^高B细胞（全球1106例测定）。我们通过线性或回归模型测试了B-reg与相关变量之间的关联，以进行重复测量，并根据Tx调整时间。

结果

在多变量分析中分析的所有变量中，包括慢性排斥反应（OR − 0.19，p  = .039），霉酚酸酯的使用（OR − 0.38，p  <.001）和金黄色葡萄球菌的肺部感染（OR 0.66，p  = .002）和烟曲霉（OR 0.50，p  = .009）与B-reg细胞显着相关。

在我们的队列中未发现CD19 + CD24^高CD38^高B-reg细胞与T-reg细胞计数之间的显着相关性。

结论

我们目前的数据首次凸显了该细胞亚群可能参与了长期的肺移植接受机制。