Increased Autoantibodies Against Ro/SS-A, CENP-B, and La/SS-B in Patients With Kidney Allograft Antibody-mediated Rejection.
Increased Autoantibodies Against Ro/SS-A, CENP-B, and La/SS-B in Patients With Kidney Allograft Antibody-mediated Rejection.
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DOI：
10.1097/txd.0000000000001215
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发表时间：
2021-10
影响因子：
2.3
通讯作者：
Konvalinka A
中科院分区：
文献类型：
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作者：
Clotet-Freixas S;Kotlyar M;McEvoy CM;Pastrello C;Rodríguez-Ramírez S;Farkona S;Cardinal H;Dieudé M;Hébert MJ;Li Y;Famure O;Chen P;Kim SJ;Chan E;Jurisica I;John R;Chruscinski A;Konvalinka A
补充数字内容可在文本中找到。抗体介导的排斥反应（AMR）导致超过50%的晚期肾移植物丢失。除了抗人类白细胞抗原（HLA）供体特异性抗体外，抗非HLA抗原的抗体也与AMR相关。识别关键的非HLA抗体将提高我们对AMR的理解。我们分析了80例肾移植患者血清中的非HLA抗体，这些患者患有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。在移植前或诊断时收集的血清样本中测量针对134种非HLA抗原的IgM和IgG抗体。AMR和混合性排斥反应组中有15例非HLA抗体较移植前ACR或急性肾小管坏死组显著升高（P < 0.05），7例非HLA抗体在诊断时显著升高（P < 0.05）。与ACR相比，AMR和混合病例显示移植前IgG抗Ro/Sjögren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AMR/混合性排斥中显著增加。IgG抗Ro/SS-A、IgG抗CENP-B和IgM抗La/SS-B的升高与微血管病变和II类供者特异性抗体的存在相关（P < 0.05）。与ACR相比，在60例肾移植患者的外部队列中，AMR/混合性排斥反应中IgG抗Ro/SS-A和IgM抗CENP-B抗体显著增加。这是第一项涉及AMR中自身抗体抗Ro/SS-A和抗CENP-B的研究。这些抗体可能参与肾脏AMR中自身免疫和同种免疫之间的相互作用。
Supplemental Digital Content is available in the text. 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 (P < 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 (P < 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.