B-cell immunity in the context of T-cell tolerance after combined kidney and bone marrow transplantation in humans.
B-cell immunity in the context of T-cell tolerance after combined kidney and bone marrow transplantation in humans.
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DOI：
10.1111/j.1600-6143.2009.02738.x
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发表时间：
2009-09
期刊：
影响因子：
--
通讯作者：
Zorn E
中科院分区：
文献类型：
--
作者：
Porcheray F;Wong W;Saidman SL;De Vito J;Girouard TC;Chittenden M;Shaffer J;Tolkoff-Rubin N;Dey BR;Spitzer TR;Colvin RB;Cosimi AB;Kawai T;Sachs DH;Sykes M;Zorn E
5例终末期肾病患者在非清髓性预处理后接受HLA半相合供者的肾和骨髓联合移植，以诱导肾移植耐受。4例患者成功中止免疫抑制治疗，随后随访3至6年以上。这种同种异体移植物接受伴随着特异性T细胞对供体抗原的无反应性。然而，这4例患者中有2例在移植后1 - 2年出现了与供体抗原反应的新生抗体。这些体液反应的特征是血清中存在供体HLA特异性抗体，移植物中有或没有补体分子C4 d沉积。免疫荧光染色，ELISA检测和抗体分析使用蛋白质微阵列证明了在这两个病人的自身抗体和同种抗体的共同发展。这些反应之前血清BAFF水平升高，并与B细胞重建相一致，如外周中高频率的过渡性B细胞所揭示的。迄今为止，这些B细胞应答与体液排斥的证据无关，其临床意义仍不清楚。总的来说，我们的研究结果表明，在T细胞对供体移植物耐受的患者中，B细胞同种和自身免疫的发展。
Five patients with end-stage kidney disease received combined kidney and bone marrow transplants from HLA haploidentical donors following nonmyeloablative conditioning to induce renal allograft tolerance. Immunosuppressive therapy was successfully discontinued in four patients with subsequent follow-up of 3 to more than 6 years. This allograft acceptance was accompanied by specific T-cell unresponsiveness to donor antigens. However, two of these four patients showed evidence of de novo antibodies reactive to donor antigens between 1 and 2 years posttransplant. These humoral responses were characterized by the presence of donor HLA-specific antibodies in the serum with or without the deposition of the complement molecule C4d in the graft. Immunofluorescence staining, ELISA assays and antibody profiling using protein microarrays demonstrated the co-development of auto- and alloantibodies in these two patients. These responses were preceded by elevated serum BAFF levels and coincided with B-cell reconstitution as revealed by a high frequency of transitional B cells in the periphery. To date, these B cell responses have not been associated with evidence of humoral rejection and their clinical significance is still unclear. Overall, our findings showed the development of B-cell allo- and autoimmunity in patients with T-cell tolerance to the donor graft.
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影响因子：
6.2
作者：
Lee, PC;Terasaki, PI;Lei, HY
通讯作者：
Lei, HY
影响因子：
4.4
作者：
Marina, Ovidiu;Biernacki, Melinda A.;Wu, Catherine J.
通讯作者：
Wu, Catherine J.
影响因子：
158.5
作者：
Kawai, Tatsuo;Cosimi, A. Benedict;Sachs, David H.
通讯作者：
Sachs, David H.
影响因子：
56.9
作者：
Bernasconi, NL;Traggiai, E;Lanzavecchia, A
通讯作者：
Lanzavecchia, A
DOI：
10.1080/00365510701342062
发表时间：
2007-01-01
影响因子：
2.1
作者：
Beyer, N. H.;Milthers, J.;Frederiksen, J. Lautrup
通讯作者：
Frederiksen, J. Lautrup