Wiebe C, Gareau A J, Pochinco D, Gibson I W, Ho J, Birk P E, Blydt-Hansen T, Karpinski M, Goldberg A, Storsley L, Rush D N, Nickerson P W
Department of Medicine, University of Manitoba, Winnipeg, Canada.
Diagnostic Services of Manitoba, Winnipeg, Canada.
Am J Transplant. 2017 Mar;17(3):703-711. doi: 10.1111/ajt.14015. Epub 2016 Oct 3.
De novo donor-specific antibodies (dnDSAs) that develop after renal transplantation are independent predictors of allograft loss. However, it is unknown if dnDSA C1q status or titer at the time of first detection can independently predict allograft loss. In a consecutive cohort of 508 renal transplant recipients, 70 developed dnDSAs. Histologic and clinical outcomes were correlated with the C1q assay or dnDSA titer. C1q positivity correlated with dnDSA titer (p < 0.01) and mean fluorescence intensity (p < 0.01) and was more common in class II versus class I dnDSAs (p < 0.01). C1q status correlated with tubulitis (p = 0.02) and C4d status (p = 0.03) in biopsies at the time of dnDSA development, but not T cell-mediated rejection (TCMR) or antibody-mediated rejection (ABMR). De novo DSA titer correlated with Banff g, i, t, ptc, C4d scores, TCMR (p < 0.01) and ABMR (p < 0.01). Post-dnDSA graft loss was observed more frequently in recipients with C1q-positve dnDSA (p < 0.01) or dnDSA titer ≥ 1:1024 (p ≤ 0.01). However, after adjustment for clinical phenotype and nonadherence in multivariate models, neither C1q status nor dnDSA titer were independently associated with allograft loss, questioning the utility of these assays at the time of dnDSA development.
肾移植后产生的新生供者特异性抗体(dnDSAs)是移植肾丢失的独立预测指标。然而,首次检测时dnDSA的C1q状态或滴度是否能独立预测移植肾丢失尚不清楚。在508例连续性肾移植受者队列中,70例产生了dnDSAs。组织学和临床结局与C1q检测或dnDSA滴度相关。C1q阳性与dnDSA滴度(p<0.01)和平均荧光强度(p<0.01)相关,在Ⅱ类dnDSA中比Ⅰ类更常见(p<0.01)。在dnDSA产生时的活检中,C1q状态与肾小管炎(p = 0.02)和C4d状态(p = 0.03)相关,但与T细胞介导的排斥反应(TCMR)或抗体介导的排斥反应(ABMR)无关。新生DSA滴度与Banff g、i、t、ptc、C4d评分、TCMR(p<0.01)和ABMR(p<0.01)相关。C1q阳性dnDSA(p<0.01)或dnDSA滴度≥1:1024(p≤0.01)的受者中,dnDSA出现后移植肾丢失更常见。然而,在多变量模型中对临床表型和不依从性进行校正后,C1q状态和dnDSA滴度均与移植肾丢失无独立相关性,这对dnDSA产生时这些检测的实用性提出了质疑。