Schuster A, Jung B, Hofbauer J, Kühne L, Zecher D, Banas B, Bergler T
Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
Department of Nephrology, University Hospital Regensburg, Regensburg, Germany.
Transpl Immunol. 2017 Dec;45:35-41. doi: 10.1016/j.trim.2017.08.006. Epub 2017 Sep 1.
The B-cell activating factor BAFF plays an important role in the development and maturation of B-lymphocytes, which can contribute to the generation of donor-specific antibodies and thus may influence graft function and graft survival. Inconsistent data on the role of BAFF levels after renal transplantation for the formation of donor-specific antibodies and the contribution for allograft rejection exist. The aim of the current study was to determine to what extent the degree of pre-immunization is reflected by each patient's BAFF levels before transplantation and in the follow-up. Furthermore, the impact of BAFF on allograft rejection frequency as well as severity and resulting allograft function over time was analyzed. Additionally, the impact of viral infections on BAFF levels after transplantation - as a potential confounder - was examined. For this purpose, a group of pre-sensitized patients (PRA>0%, (52±24% on average), n=40) was compared with non-sensitized patients (PRA=0%, n=62) and in a subsequent analysis stratification in accordance to the detected BAFF level was performed. Pre-sensitized patients had significantly higher BAFF levels before transplantation and suffered significantly more often from early steroid-resistant, mainly antibody-mediated rejections. A result which was confirmed also in highly sensitized patients with PRA levels >50%. Additionally, in the follow-up patients with either rising BAFF levels over time or BAFF levels above the median also had significantly more often antibody mediated rejections. Additionally, patients with BAFF levels above detected median even displayed impaired creatinine values as well as an induced eGFR slope up to month 48 after transplantation. The occurrence of viral infections (CMV, BKV) was only an additional influencing factor in the absence of concomitant allograft rejections. Therefore, the B-cell proliferation factor BAFF appears not only to reflect the immunological risk profile of patients in the context of kidney transplantation, it may possibly be further developed as a predictor of patients with an increased risk profile for subsequent allograft rejection and impaired allograft function.
B细胞活化因子BAFF在B淋巴细胞的发育和成熟过程中发挥着重要作用，它可促使产生供体特异性抗体，进而可能影响移植器官的功能和存活。关于肾移植后BAFF水平在供体特异性抗体形成中的作用以及对同种异体移植排斥反应的影响，目前的数据并不一致。本研究的目的是确定移植前及随访中每位患者的BAFF水平在多大程度上反映了免疫前状态。此外，分析了BAFF对同种异体移植排斥反应频率、严重程度以及随时间推移对移植器官功能的影响。另外，还研究了病毒感染作为一个潜在混杂因素对移植后BAFF水平的影响。为此，将一组预致敏患者（群体反应性抗体>0%，平均为(52±24%)，n = 40）与未致敏患者（群体反应性抗体 = 0%，n = 62）进行比较，并在后续分析中根据检测到的BAFF水平进行分层。预致敏患者在移植前的BAFF水平显著更高，且更常发生早期激素抵抗性排斥反应，主要是抗体介导的排斥反应。这一结果在群体反应性抗体水平>50%的高度致敏患者中也得到了证实。此外，在随访中，BAFF水平随时间升高或高于中位数的患者也更常发生抗体介导的排斥反应。此外，BAFF水平高于检测中位数的患者在移植后48个月时甚至出现肌酐值受损以及估算肾小球滤过率斜率下降。病毒感染（巨细胞病毒、BK病毒）的发生仅在无伴随同种异体移植排斥反应的情况下才是一个额外的影响因素。因此，B细胞增殖因子BAFF似乎不仅能反映肾移植患者的免疫风险状况，还可能进一步发展成为预测后续同种异体移植排斥反应风险增加及移植器官功能受损患者的指标。
