Crichton Emma S, Zeng Shan, La Muraglia G Michael, Badell I Raul
Emory Transplant Center, Atlanta, GA.
Transplant Direct. 2021 Nov 5;7(12):e785. doi: 10.1097/TXD.0000000000001247. eCollection 2021 Dec.
Donor-specific antibodies (DSA) are a recognized cause of allograft injury, yet biomarkers that indicate their development posttransplant or guide management are not available. CXCL13 (chemokine [C-X-C motif] ligand 1) is a chemoattractant produced within secondary lymphoid organs necessary for germinal center (GC) and alloantibody formation. Perturbations in serum CXCL13 levels have been associated with humoral immune activity. Therefore, CXCL13 may correlate with the formation of HLA antibodies following transplantation.
A murine skin graft model was utilized to define the production and kinetics of CXCL13 in response to alloantigen. Human Tfh:B-cell in vitro cocultures were performed to evaluate CXCL13 production by human lymphocytes, and serum from healthy controls and human transplant recipients with and without de novo DSA was tested for CXCL13.
CXCL13 was detectable in the blood of allografted mice and correlated with Tfh and GC B-cell responses. Greater CXCL13 expression was observed in the draining lymph nodes of allografted mice as compared with naïve or syngeneic graft recipients, and serum levels preceded the detection of DSA posttransplant. Similarly, productive human Tfh:B-cell interactions that led to plasmablast differentiation and IgG formation also exhibited CXCL13 expression. CXCL13 levels in human transplant recipients with de novo DSA were greater than in healthy controls and stable transplant patients and also correlated with the development of alloantibodies in a small cohort of serially monitored recipients.
CXCL13 indicates GC alloreactivity and alloantibody formation and correlated with DSA formation in kidney transplant recipients, thereby introducing CXCL13 as a potential biomarker for HLA antibodies.
供体特异性抗体（DSA）是同种异体移植损伤的公认原因，但尚无能够指示其移植后产生或指导治疗的生物标志物。CXCL13（趋化因子[C-X-C基序]配体1）是生发中心（GC）和同种异体抗体形成所必需的二级淋巴器官内产生的一种趋化因子。血清CXCL13水平的扰动与体液免疫活性相关。因此，CXCL13可能与移植后HLA抗体的形成相关。
利用小鼠皮肤移植模型来确定CXCL13对同种异体抗原反应的产生和动力学。进行人Tfh:B细胞体外共培养以评估人淋巴细胞产生CXCL13的情况，并检测健康对照以及有或无新生DSA的人类移植受者血清中的CXCL13。
在同种异体移植小鼠的血液中可检测到CXCL13，且与Tfh和GC B细胞反应相关。与未处理或同基因移植受体相比，在同种异体移植小鼠的引流淋巴结中观察到更高的CXCL13表达，并且血清水平在移植后DSA检测之前就已出现。同样，导致浆母细胞分化和IgG形成的有效的人Tfh:B细胞相互作用也表现出CXCL13表达。有新生DSA的人类移植受者的CXCL13水平高于健康对照和稳定移植患者，并且在一小群接受连续监测的受者中也与同种异体抗体的产生相关。
CXCL13指示GC同种异体反应性和同种异体抗体形成，并与肾移植受者的DSA形成相关，从而将CXCL13引入作为HLA抗体的潜在生物标志物。
