Chang Youngil, Shah Tariq, Min David I
Mendez National Institute of Transplantation, Los Angeles, CA, United States; Western University of Health Sciences, Pomona, CA, United States.
Mendez National Institute of Transplantation, Los Angeles, CA, United States; Western University of Health Sciences, Pomona, CA, United States; St. Vincent Medical Center, Los Angeles, CA, United States.
Hum Immunol. 2017 Oct;78(10):621-628. doi: 10.1016/j.humimm.2017.06.001. Epub 2017 Jun 15.
The posttransplant development of donor specific antibodies (DSA) initiates the antibody mediated rejection (AMR), which is associated with the increased rate of graft loss. One of the characteristics of AMR is the infiltration of innate immune system including macrophages, monocytes, neutrophils or NK cells. Macrophage inhibitory factor (MIF) and B-cell activating factor (BAFF) are well known cytokines that are associated with the activation of the innate immune system which can damage kidney allograft. In this article, the association of the genetic polymorphisms of MIF and BAFF with the development of DSA including Class I and II in kidney transplant patients is investigated. A total of 231 renal transplant patients between 2008 and 2012 at St. Vincent Medical Center, CA were studied in a retrospective study design. DSA were determined by Luminex technology, and single nucleotide polymorphisms (SNP) of MIF and BAFF were determined by the real time PCR based on 5' nuclease allelic discrimination assay. The genetic polymorphisms of MIF rs1007888 (C/T) was associated with increased risk of positive DSA detection (p=0.04) after transplantation, and consistently significant after 1year (p=0.016). Furthermore, the presence of C allele were associated with the increased risk of Class I DSA detection (OR 1.816, CI 1.141-2.889, p=0.011). Also, genetic polymorphisms of BAFF rs12583006 were associated with the increased risk of Class II DSA detection (p=0.033). In conclusion, the genetic polymorphisms of MIF and BAFF may increase the risk of posttransplant development of DSA. This result suggests the association between the development of posttransplant DSA and the activation of innate immune system.
移植后供者特异性抗体（DSA）的产生引发了抗体介导的排斥反应（AMR），这与移植肾丢失率增加相关。AMR的特征之一是固有免疫系统的浸润，包括巨噬细胞、单核细胞、中性粒细胞或自然杀伤细胞。巨噬细胞抑制因子（MIF）和B细胞活化因子（BAFF）是众所周知的细胞因子，它们与可损害肾移植的固有免疫系统激活有关。在本文中，研究了肾移植患者中MIF和BAFF基因多态性与包括I类和II类DSA产生之间的关联。采用回顾性研究设计，对2008年至2012年期间加利福尼亚州圣文森特医疗中心的231例肾移植患者进行了研究。通过Luminex技术检测DSA，基于5'核酸酶等位基因鉴别分析的实时PCR法检测MIF和BAFF的单核苷酸多态性（SNP）。MIF rs1007888（C/T）基因多态性与移植后DSA检测阳性风险增加相关（p = 0.04），1年后仍具有显著意义（p = 0.016）。此外，C等位基因的存在与I类DSA检测风险增加相关（OR 1.816，CI 1.141 - 2.889，p = 0.011）。同样，BAFF rs12583006基因多态性与II类DSA检测风险增加相关（ p = 0.033）。总之，MIF和BAFF基因多态性可能增加移植后DSA产生的风险。这一结果提示了移植后DSA产生与固有免疫系统激活之间的关联。
