Use of complement binding assays to assess the efficacy of antibody mediated rejection therapy and prediction of graft survival in kidney transplantation

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• 作者：Daniel S. Ramon^a ; ^{dramon@stanford.edu} ; Yihung Huang^b ; Lili Zhao^c ; TrisAnn Rendulic^d ; Jeong M. Park^d ; Randall S. Sung^e ; Milagros Samaniego^b
• 关键词：AMR ; antibody-mediated rejection ; DSA ; donor-specific antibody ; HEL ; high expression loci ; IVIG ; intravenous immunoglobulin ; LEL ; low expression loci ; MFI ; mean fluorescent intensity ; NR ; nonresponders ; R ; responders ; SAB ; single antigen bead Luminex® ; assay
• 刊名：Human Immunology
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：78
• 期：2
• 页码：57-63
• 全文大小：1192 K
• 卷排序：78

文摘

The Luminex® single antigen bead assay (SAB) is the method of choice for monitoring the treatment for antibody-mediated rejection (AMR). A ⩾50% reduction of the dominant donor-specific antibody (IgG-DSA) mean fluorescence intensity (MFI) has been associated with improved kidney allograft survival, and C1q-fixing DSA activity is associated with poor outcomes in patients with AMR. We aimed to investigate if C1q-DSA can be used as a reliable predictor of response to therapy and allograft survival in patients with biopsy-proven AMR.MethodsWe tested pre- and post-treatment sera of 30 kidney transplant patients receiving plasmapheresis and low-dose IVIG for biopsy-proven AMR. IgG-DSA and C1q-DSA MFI were measured and correlated with graft loss or survival. Patients were classified as nonresponders (NR) when treatment resulted in <50% reduction in MFI of IgG-DSA and/or C1q-DSA was detectable following therapy.ResultsDifferences in the percentage of patients deemed NR depended upon the end-point criterion (73% by reduction in IgG-DSA MFI vs. 50% by persistent C1q-DSA activity). None of the seven patients with <50% reduction of IgG-DSA but non-detectable C1q-DSA-fixing activity after therapy experienced graft loss, suggesting that C1q-DSA activity may better correlate with response. Reduction of C1q-DSA activity predicted graft survival better than IgG-DSA in the univariate Cox analysis (20.1% vs. 5.9% in NR; log-rank P-value = 0.0147).ConclusionsA rapid reduction of DSA concentration below the threshold required for complement activation is associated with better graft survival, and C1q-DSA is a better predictor of outcomes than IgG-DSA MFI reduction.