O'Leary Jacqueline G, Farris Alton B, Gebel Howard M, Asrani Sumeet K, Askar Medhat, Garcia Vanessa, Snipes George J, Lo Denise J, Knechtle Stuart J, Klintmalm Goran B, Demetris Anthony J
Department of Medicine, Dallas VA Medical Center, Dallas, TX.
Department of Pathology, Emory University Hospital, Atlanta, GA.
Transplant Direct. 2023 Jul 12;9(8):e1500. doi: 10.1097/TXD.0000000000001500. eCollection 2023 Aug.
Liver allografts protect renal allografts from the same donor from some, but not all, preformed donor specific alloantibodies (DSA). However, the precise mechanisms of protection and the potential for more subtle alterations/injuries within the grafts resulting from DSA interactions require further study.
We reevaluated allograft biopsies from simultaneous liver-kidney transplant recipients who had both allografts biopsied within 60 d of one another and within 30 d of DSA being positive in serum (positive: mean florescence intensity ≥5000). Routine histology, C4d staining, and specialized immunohistochemistry for Kupffer cells (KCs; CD163) and a C4d receptor immunoglobulin-like transcript-4 were carried out in 4 patients with 6 paired biopsies.
Overt antibody-mediated rejection was found in 3 of 4 renal and liver allografts. One patient had biopsy-confirmed renal and liver allograft antibody-mediated rejection despite serum clearance of DSA. All biopsies showed KC hypertrophy (minimal: 1; mild: 2; moderate: 1; severe: 2) and cytoplasmic C4d KC staining was easily detected in 2 biopsies from 2 patients; minimal and negative in 2 biopsies each. Implications of which are discussed. Control 1-y protocol liver allograft biopsies from DSA- recipients showed neither KC hypertrophy nor KC C4d staining (n = 6).
Partial renal allograft protection by a liver allograft from the same donor may be partially mediated by phagocytosis/elimination of antibody and complement split products by KCs, as shown decades ago in controlled sensitized experimental animal experiments.
肝脏同种异体移植可保护来自同一供体的肾脏同种异体移植免受部分(而非全部)预先形成的供体特异性同种异体抗体(DSA)的影响。然而,保护的确切机制以及DSA相互作用导致移植物内更细微改变/损伤的可能性仍需进一步研究。
我们重新评估了同期肝肾移植受者的同种异体移植活检标本,这些受者的两个同种异体移植在彼此60天内以及血清DSA呈阳性(阳性:平均荧光强度≥5000)后30天内进行了活检。对4例患者的6对活检标本进行了常规组织学、C4d染色以及针对库普弗细胞(KC;CD163)和C4d受体免疫球蛋白样转录本-4的特殊免疫组织化学检查。
4例肾和肝同种异体移植中有3例发现明显的抗体介导排斥反应。1例患者尽管血清DSA清除,但活检证实肾和肝同种异体移植存在抗体介导排斥反应。所有活检均显示KC肥大(轻度:1例;中度:1例;重度:2例),2例患者的2份活检标本中很容易检测到细胞质C4d KC染色;另外2份活检标本中分别为轻度和阴性。对此的影响进行了讨论。来自DSA阴性受者的对照1年方案肝同种异体移植活检标本既未显示KC肥大也未显示KC C4d染色(n = 6)。
来自同一供体的肝脏同种异体移植对肾脏同种异体移植的部分保护可能部分由KC对抗体和补体裂解产物的吞噬/清除介导,正如数十年前在对照致敏实验动物实验中所显示的那样。