To seek insights into the pathogenesis of chronic active antibody–mediated rejection (CAMR), we performed mRNA analysis and correlated transcripts with pathologic component scores and graft outcomes.

We utilized the NanoString nCounter platform and the Banff Human Organ Transplant gene panel to quantify transcripts on 326 archived renal allograft biopsy samples. This system allowed correlation of transcripts with Banff pathology scores from the same tissue block and correlation with long-term outcomes.

The only pathology score that correlated with AMR pathways in CAMR was peritubular capillaritis (ptc). C4d, cg, g, v, i, t, or ci scores did not correlate. DSA-negative CAMR had lower AMR pathway scores than DSA-positive CAMR. Transcript analysis in non-CAMR biopsies yielded evidence of increased risk of later CAMR. Among 108 patients without histologic CAMR, 23 developed overt biopsy-documented CAMR within 5 years and as a group had higher AMR pathway scores (P=3.4 x 10^–5). Random forest analysis correlated 3-year graft loss with elevated damage, innate immunity, and macrophage pathway scores in CAMR and TCMR. Graft failure in CAMR was associated with TCMR transcripts but not with AMR transcripts, and graft failure in TCMR was associated with AMR transcripts but not with TCMR transcripts.

Peritubular capillary inflammation and DSA are the primary drivers of AMR transcript elevation. Transcripts revealed subpathological evidence of AMR, which often preceded histologic CAMR and subpathological evidence of TCMR that predicted graft loss in CAMR.

为了深入了解慢性活性抗体介导的排斥反应 (CAMR) 的发病机制，我们进行了 mRNA 分析并将转录本与病理成分评分和移植物结果相关联。

我们利用 NanoString nCounter 平台和班夫人体器官移植基因组对 326 个存档的肾同种异体移植活检样本的转录本进行量化。该系统允许将转录本与来自同一组织块的班夫病理学评分相关联，并与长期结果相关联。

CAMR 中唯一与 AMR 通路相关的病理评分是管周毛细血管炎 (ptc)。C4d、cg、g、v、i、t 或 ci 分数不相关。DSA 阴性 CAMR 的 AMR 通路评分低于 DSA 阳性 CAMR。非 CAMR 活组织检查的转录本分析产生了后期 CAMR 风险增加的证据。在 108 名没有组织学 CAMR 的患者中，23 名在 5 年内发展为明显的活检记录的 CAMR，并且作为一个组具有更高的 AMR 通路评分（P = 3.4 x 10 ^–5). 随机森林分析将 3 年移植物丢失与 CAMR 和 TCMR 中损伤、先天免疫和巨噬细胞通路评分升高相关联。CAMR 中的移植物失败与 TCMR 转录物相关，但与 AMR 转录物无关，而 TCMR 中的移植物失败与 AMR 转录物相关，但与 TCMR 转录物无关。

管周毛细血管炎症和 DSA 是 AMR 转录物升高的主要驱动因素。转录本揭示了 AMR 的亚病理学证据，这通常先于组织学 CAMR 和预测 CAMR 移植物丢失的 TCMR 亚病理学证据。