Huibers M M H, Gareau A J, Beerthuijzen J M T, Siera-de Koning E, van Kuik J, Kamburova E G, Vink A, de Jonge N, Lee T D G, Otten H G, de Weger R A
Department of Pathology, University Medical Center Utrecht, Utrecht, the Netherlands.
Department of Internal Medicine, University of Manitoba, Winnipeg, Canada.
Am J Transplant. 2017 Jan;17(1):246-254. doi: 10.1111/ajt.13969. Epub 2016 Aug 18.
Cardiac allograft vasculopathy (CAV) is a transplant pathology, limiting graft survival after heart transplantation. CAV arteries are surrounded by ectopic lymphoid structures (ELS) containing B cells and plasma cells. The aim of this study was to characterize the antigenic targets of antibodies produced in ELS. Coronary arteries and surrounding epicardial tissue from 56 transplant recipients were collected during autopsy. Immunofluorescence was used to identify antibody-producing plasma cells. Immunoglobulin levels in tissue lysates were measured by enzyme-linked immunosorbent assay and analyzed for donor-specific HLA antibodies by Luminex assay. Cytokine and receptor expression levels were quantified using quantitative polymerase chain reaction. Plasma cells in ELS were polyclonal and produced IgG and/or IgM antibodies. In epicardial tissue, IgG (p < 0.05) and IgM levels were higher in transplant patients with larger ELS than smaller ELS. In 4 of 21 (19%) patients with ELS, donor-specific HLA type II antibodies were detected locally. Cytokine and receptor expression (CXCR3, interferon γ and TGF-β) was higher in large ELS in the epicardial tissue than in other vessel wall layers, suggesting active recruitment and proliferation of T and B lymphocytes. ELS exhibited active plasma cells producing locally manufactured antibodies that, in some cases, were directed against the donor HLA, potentially mediating rejection with major consequences for the graft.
心脏移植血管病变（CAV）是一种移植病理学疾病，会限制心脏移植后的移植物存活。CAV动脉被含有B细胞和浆细胞的异位淋巴样结构（ELS）所包围。本研究的目的是鉴定ELS中产生的抗体的抗原靶点。在尸检过程中收集了56名移植受者的冠状动脉及周围的心外膜组织。采用免疫荧光法鉴定产生抗体的浆细胞。通过酶联免疫吸附测定法测量组织裂解物中的免疫球蛋白水平，并通过Luminex测定法分析供体特异性HLA抗体。使用定量聚合酶链反应对细胞因子和受体表达水平进行定量。ELS中的浆细胞是多克隆的，产生IgG和/或IgM抗体。在心外膜组织中，ELS较大的移植患者的IgG（p < 0.05）和IgM水平高于ELS较小的患者。在21名（19%）有ELS的患者中，有4名患者局部检测到供体特异性HLA II类抗体。心外膜组织中大型ELS的细胞因子和受体表达（CXCR3、干扰素γ和转化生长因子-β）高于其他血管壁层，提示T和B淋巴细胞的活跃募集和增殖。ELS表现出活跃的浆细胞产生局部制造的抗体，在某些情况下，这些抗体针对供体HLA，可能介导排斥反应，对移植物产生重大影响。
