Clotet-Freixas Sergi, Kotlyar Max, McEvoy Caitriona M, Pastrello Chiara, Rodríguez-Ramírez Sonia, Farkona Sofia, Cardinal Heloise, Dieudé Mélanie, Hébert Marie-Josée, Li Yanhong, Famure Olusegun, Chen Peixuen, Kim S Joseph, Chan Emilie, Jurisica Igor, John Rohan, Chruscinski Andrzej, Konvalinka Ana
Toronto General Hospital Research Institute, University Health Network, Toronto, Canada.
Soham and Shaila Ajmera Family Transplant Centre, University Health Network, Toronto, Canada.
Transplant Direct. 2021 Sep 20;7(10):e768. doi: 10.1097/TXD.0000000000001215. eCollection 2021 Oct.
Antibody-mediated rejection (AMR) causes more than 50% of late kidney graft losses. In addition to anti-human leukocyte antigen (HLA) donor-specific antibodies, antibodies against non-HLA antigens are also linked to AMR. Identifying key non-HLA antibodies will improve our understanding of AMR.
We analyzed non-HLA antibodies in sera from 80 kidney transplant patients with AMR, mixed rejection, acute cellular rejection (ACR), or acute tubular necrosis. IgM and IgG antibodies against 134 non-HLA antigens were measured in serum samples collected pretransplant or at the time of diagnosis.
Fifteen non-HLA antibodies were significantly increased ( < 0.05) in AMR and mixed rejection compared with ACR or acute tubular necrosis pretransplant, and 7 at diagnosis. AMR and mixed cases showed significantly increased pretransplant levels of IgG anti-Ro/Sjögren syndrome-antigen A (SS-A) and anti-major centromere autoantigen (CENP)-B, compared with ACR. Together with IgM anti-CENP-B and anti-La/SS-B, these antibodies were significantly increased in AMR/mixed rejection at diagnosis. Increased IgG anti-Ro/SS-A, IgG anti-CENP-B, and IgM anti-La/SS-B were associated with the presence of microvascular lesions and class-II donor-specific antibodies ( < 0.05). Significant increases in IgG anti-Ro/SS-A and IgM anti-CENP-B antibodies in AMR/mixed rejection compared with ACR were reproduced in an external cohort of 60 kidney transplant patients.
This is the first study implicating autoantibodies anti-Ro/SS-A and anti-CENP-B in AMR. These antibodies may participate in the crosstalk between autoimmunity and alloimmunity in kidney AMR.
抗体介导的排斥反应（AMR）导致超过50%的晚期肾移植失败。除了抗人白细胞抗原（HLA）供体特异性抗体外，抗非HLA抗原的抗体也与AMR有关。识别关键的非HLA抗体将增进我们对AMR的理解。
我们分析了80例发生AMR、混合性排斥反应、急性细胞排斥反应（ACR）或急性肾小管坏死的肾移植患者血清中的非HLA抗体。在移植前或诊断时采集的血清样本中检测了针对134种非HLA抗原的IgM和IgG抗体。
与移植前的ACR或急性肾小管坏死相比，AMR和混合性排斥反应中有15种非HLA抗体显著增加（<0.05），诊断时为7种。与ACR相比，AMR和混合性病例在移植前IgG抗Ro/干燥综合征抗原A（SS-A）和抗主要着丝粒自身抗原（CENP）-B水平显著升高。与IgM抗CENP-B和抗La/SS-B一起，这些抗体在诊断时的AMR/混合性排斥反应中显著增加。IgG抗Ro/SS-A、IgG抗CENP-B和IgM抗La/SS-B升高与微血管病变和II类供体特异性抗体的存在相关（<0.05）。在60例肾移植患者的外部队列中重现了与ACR相比，AMR/混合性排斥反应中IgG抗Ro/SS-A和IgM抗CENP-B抗体的显著增加。
这是第一项表明自身抗体抗Ro/SS-A和抗CENP-B与AMR有关的研究。这些抗体可能参与了肾AMR中自身免疫和同种免疫之间的相互作用。
