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Association of early kidney allograft failure with preformed IgA antibodies to ?2-glycoprotein I.

ABSTRACT: In the current immunosuppressive therapy era, vessel thrombosis is the most common cause of early graft loss after renal transplantation. The prevalence of IgA anti-?2-glycoprotein I antibodies (IgA-aB2GPI-ab) in patients on dialysis is elevated (>30%), and these antibodies correlate with mortality and cardiovascular morbidity. To evaluate the effect of IgA-aB2GPI-ab in patients with transplants, we followed all patients transplanted from 2000 to 2002 in the Hospital 12 de Octubre prospectively for 10 years. Presence of IgA-aB2GPI-ab in pretransplant serum was examined retrospectively. Of 269 patients, 89 patients were positive for IgA-aB2GPI-ab (33%; group 1), and the remaining patients were negative (67%; group 2). Graft loss at 6 months post-transplant was significantly higher in group 1 (10 of 89 versus 3 of 180 patients in group 2; P=0.002). The most frequent cause of graft loss was thrombosis of the vessels, which was observed only in group 1 (8 of 10 versus 0 of 3 patients in group 2; P=0.04). Multivariate analysis showed that the presence of IgA-aB2GPI-ab was an independent risk factor for early graft loss (P=0.04) and delayed graft function (P=0.04). There were no significant differences regarding patient survival between the two groups. Graft survival was similar in both groups after 6 months. In conclusion, patients with pretransplant IgA-aB2GPI-ab have a high risk of early graft loss caused by thrombosis and a high risk of delayed graft function. Therefore, pretransplant IgA-aB2GPI-ab may have a detrimental effect on early clinical outcomes after renal transplantation.

SUBMITTER: Morales JM

PROVIDER: S-EPMC4341482 | biostudies-other | 2015 Mar

REPOSITORIES: biostudies-other

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Association of early kidney allograft failure with preformed IgA antibodies to β2-glycoprotein I.

Morales Jose M JM Martinez-Flores Jose Angel JA Serrano Manuel M Castro Maria José MJ Alfaro Francisco Javier FJ García Florencio F Martínez Miguel Angel MA Andrés Amado A González Esther E Praga Manuel M Paz-Artal Estela E Serrano Antonio A

Journal of the American Society of Nephrology : JASN 20140728 3

In the current immunosuppressive therapy era, vessel thrombosis is the most common cause of early graft loss after renal transplantation. The prevalence of IgA anti-β2-glycoprotein I antibodies (IgA-aB2GPI-ab) in patients on dialysis is elevated (>30%), and these antibodies correlate with mortality and cardiovascular morbidity. To evaluate the effect of IgA-aB2GPI-ab in patients with transplants, we followed all patients transplanted from 2000 to 2002 in the Hospital 12 de Octubre prospectively ...[more]

PMID: 25071084

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Project description:The consolidation of single antigen beads (SAB-panIgG) assay in the detection of preformed anti-human leukocyte antigen (HLA) antibodies has improved transplantation success. However, its high sensitivity has limited the allograft allocation for sensitized patients, increasing their waiting time. A modification of the standard SAB-panIgG assay allows the detection of that subset of antibodies capable of binding C1q (SAB-C1q assay). However, the clinical usefulness of SAB-C1q assay for determining the unacceptable mismatches is under discussion. We retrospectively analyzed the impact of preformed donor-specific anti-HLA antibodies (DSA) according to the C1q-binding ability on allograft outcome, examining 389 single-kidney transplanted patients from deceased donors. Recipients with preformed C1q-binding DSA showed the lowest allograft survival up to 7?years (40.7%) compared to patients with preformed non-C1q-binding DSA (73.4%; p?=?0.001) and without DSA (79.1%; p?<?0.001). Allograft survival rate was similar between patients with preformed non-C1q-binding DSA and patients without preformed DSA (p?=?0.403). Interestingly, among the high-mean fluorescence intensity DSA (?10,000) population (n?=?46), those patients whose DSA were further capable of binding C1q showed a poorer allograft outcome (38.4 vs. 68.9%; p?=?0.041). Moreover, in our multivariate predictive model for assessing the risk of allograft loss, the presence of C1q-binding DSA (HR 4.012; CI 95% 2.326-6.919; p?<?0.001) but not of non-C1q-binding DSA (HR 1.389; CI 95% 0.784-2.461; p?=?0.260) remained an independent predictor after stratifying the DSA population according to the C1q-binding ability and adjusting the model for other pre-transplantation predictive factors including donor age, cold-ischemia time, and HLA-DR mismatches. In conclusion, the unacceptable mismatch definition according to the SAB-C1q assay would improve the risk stratification of allograft loss and increase the limited allograft allocation of highly sensitized patients, shortening their waiting time.

Dataset Information

Association of early kidney allograft failure with preformed IgA antibodies to ?2-glycoprotein I.

Publications

Association of early kidney allograft failure with preformed IgA antibodies to β2-glycoprotein I.

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