Searching for New Biomarkers more Specific for Graft Loss after Renal Transplantation by Thrombosis: IgA aB2GPI CIC

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Abstract

Background

An important complication of kidney transplant is the graft loss, mainly by thrombosis, in the first weeks after transplantation. Early graft loss afect to 5-8% of the patients and this percentage has remained unchanged in recent decades. Prevalence of a antiphospholipid antibody: anti b2-glycoprotein-I (B2GP1) of IgA isotype in patients with chronic kidney disease is elevated (near 1/3) and has been related with thrombosis on dialysis period and allograft failure after transplantation. We described recently the association of the presence of immune-complexes of B2GP1 bounded to specific antibodies of IgA isotype with acute thrombosis, however its prospective clinical associations have not been described.

Design

Historical cohort of patients followed for two years.

Participants

All kidney-transplanted patients from 2000 to 2011 (12 years) in the Hospital 12 de Octubre (N=1375 patients).

Setting

IgA-anti-B2GP1 were evaluated in pretransplant serum and two cohorts of positive (group 1, N=401) and negative patients (group 2, N=974) were established. Patients on group 1 transplanted in the period 2008-2011 were also studied for blood-circulating immune complex (Group-1-2008, N=170).

Results

Graft loss at six post-transplant months was significantly higher in Group-1 (18% vs 7.2%; p<0.001). The most frequent cause of graft loss was vessel thrombosis, which was more frequent in group-1 than in group-2 (12.2% vs 2.6% of patients). Multivariate analysis showed that the presence of IgA-aB2GP1 antibodies was an independent risk factor (p<0.001) for early graft loss (odds ratio: 2,47, CI:1,72-3,55) and graft thrombosis (odds ratio: 5.05, CI:3.05-8.36). In group1-2008, 51 patients (30%) were positive for immune-complexes of B2GP1 bounded to IgA. Graft loss at six months was significantly higher in Immune-complex positive patients (51,1% vs 13,1%, p<0,001) Multivariate analysis showed that the presence Immune-complex was an independent risk factor for early graft loss much more powerful than the mere presence of IgA anti-B2GP1 (hazard ratio: 6,96, CI: 3,59-13,50) and for graft thrombosis (odds ratio 12.83, CI: 5,84-28,2).

Conclusions

The risk of thrombotic events and graft loss observed in patients positive for IgA anti B2GP1 is focused on those who are also positive for immune complexes. The risk on immune-complex negative patients is the same that control patients. The use of this new predictive biomarker can help to identify patients with risk of losing their graft and to establish a personalized transplantation-medicine.

Conclusions

Fondo de Investigaciones Sanitarias, cofunded by EU FEDER funds (PI14-00360).European Regional Development Funds PIE13/0045.

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