Mattel Children's Hospital UCLA, Division of Pediatric Nephrology, Los Angeles, CA, USA.
Transplantation. 2010 Oct 27;90(8):875-81. doi: 10.1097/TP.0b013e3181f24e3c.
We have previously shown that intragraft CD20+ B cells are associated with acute cellular rejection (ACR) and allograft loss. Phosphorylation of S6 ribosomal protein, a downstream target of the PI3K/Akt/mTOR pathway, promotes growth and proliferation of cells and could identify metabolically active cells such as alloantibody secreting plasma cells. Because CD20+ lymphocytes can differentiate into CD138+ plasma cells, we aimed to identify functionally active plasma cells by using intragraft CD138 quantification and p-S6RP staining and correlate these results with allograft rejection, function, and survival.
We examined 46 renal transplant biopsies from 32 pediatric patients who were biopsied for clinical suspicion of rejection. Immunohistochemical staining for C4d, CD20, CD138, and p-S6RP was performed. Patient creatinine clearance and graft status was followed up postbiopsy.
Patients with greater than or equal to six CD138+ cells/high power field (hpf) had worse graft survival with a hazard ratio of 3.4 (95% CI 1.3-9.2) 2 years postbiopsy compared with those with 0 to 5 cells/hpf (P=0.016). CD138+ cells were stained for p-S6RP, indicating functionally active plasma cells. They were associated with ACR (P=0.004) and deteriorating graft function (R=0.22, P=0.001). Intragraft CD20+ and CD138+ cells found together in ACR were associated with poorer graft survival than either marker alone, hazard ratio 1.5 (95% CI 1.1-2.2, P=0.01).
A threshold of greater than or equal to six CD138+ metabolically active plasma cells per hpf, coexisting with CD20+ B cells, was associated with poor allograft function and survival. This may represent an additional antibody-mediated process present in the setting of ACR and could play an important role in characterization and treatment of transplant rejection.
我们之前的研究表明，移植肾内的 CD20+ B 细胞与急性细胞排斥（ACR）和移植物丢失有关。PI3K/Akt/mTOR 通路的下游靶标 S6 核糖体蛋白的磷酸化可促进细胞的生长和增殖，并可识别代谢活跃的细胞，如分泌同种抗体的浆细胞。因为 CD20+淋巴细胞可分化为 CD138+浆细胞，所以我们旨在通过检测移植肾内 CD138 的定量和 p-S6RP 染色来鉴定功能活跃的浆细胞，并将这些结果与移植物排斥、功能和存活相关联。
我们对 32 名因临床怀疑排斥而接受肾活检的儿科患者的 46 例肾移植活检进行了检查。进行了 C4d、CD20、CD138 和 p-S6RP 的免疫组织化学染色。在活检后对患者的肌酐清除率和移植物状态进行了随访。
与 0 至 5 个 CD138+细胞/高倍视野（hpf）的患者相比，大于或等于 6 个 CD138+细胞/hpf 的患者在活检后 2 年的移植物存活率更差，风险比为 3.4（95%CI 1.3-9.2）（P=0.016）。CD138+细胞被染色为 p-S6RP，表明其为功能活跃的浆细胞。它们与 ACR（P=0.004）和移植物功能恶化相关（R=0.22，P=0.001）。在 ACR 中发现的与 CD20+细胞共同存在的移植肾内 CD138+细胞与单独使用任何一种标志物相比，与更差的移植物存活率相关，风险比为 1.5（95%CI 1.1-2.2，P=0.01）。
大于或等于 6 个 CD138+代谢活跃的浆细胞/ hpf 的阈值，与 CD20+B 细胞共存，与移植物功能不良和存活率差有关。这可能代表 ACR 中存在的另一种抗体介导的过程，并可能在移植排斥的特征和治疗中发挥重要作用。
