Pretransplant IgA-Anti-Beta 2 Glycoprotein I Antibodies As a Predictor of Early Graft Thrombosis after Renal Transplantation in the Clinical Practice: A Multicenter and Prospective Study

Abstract

BackgroundGraft thrombosis is a devastating complication after renal transplantation. We recently described the association of anti-beta-2-glycoprotein-I (IgA-ab2GP1) antibodies with early graft loss mainly caused by thrombosis in a monocenter study.MethodsMulticenter prospective observational cohort study.Setting and participantsSeven hundred forty patients from five hospitals of the Spanish Forum Renal Group transplanted from 2000 to 2002 were prospectively followed-up for 10 years.OutcomesEarly graft loss and graft loss by thrombosis.MeasurementsThe presence of IgA anti-B2GP1 antibodies in pretransplant serum was examined using the same methodology in all the patients.ResultsAt transplantation, 288 patients were positive for IgA-B2GP1 (39%, Group-1) and the remaining were negative (Group-2). Graft loss at 6 months was higher in Group-1 (12.5 vs. 4.2% p < 0.001), vessel thrombosis being the most frequent cause of early graft loss, especially in Group-1 (6.9 vs. 0.4% p < 0.001). IgA-aB2GP1 was the most important independent risk factor for graft thrombosis (hazard ratio: 13.83; 95% CI: 3.17–60.27, p < 0.001). Furthermore, the, presence of IgA-aB2GP1 was associated with early graft loss and delayed graft function. At 10 years, survival figures were also lower in Group-1: graft survival was lower compared with Group-2 (60.4 vs. 76.8%, p < 0.001). Mortality was significantly higher in Group-1 (19.8 vs. 12.2%, p = 0.005).LimitationsPatients were obtained during a 3-year period (1 January 2000–31 December 2002) and kidneys were only transplanted from brain-dead donors. Nowadays, the patients are older and the percentage of sensitized and retransplants is high.ConclusionIn a prospective observational multicenter study, we were able to corroborate that pretransplant presence of IgA-aB2GP1 was the main risk factor for graft thrombosis and early graft loss. Therefore, a prospective study is needed to evaluate the efficacy and safety of prophylactic anticoagulation to avoid this severe complication.

The IgA Isotype of Anti-β2 Glycoprotein I Antibodies Recognizes Epitopes in Domains 3, 4, and 5 That Are Located in a Lateral Zone of the Molecule (L-Shaped)

“…Identification by the antibodies of the IgA isotype of these zones of the molecule previously described in aPL of consensus and clearly related with the clinical signs of APS in animal models reinforces the findings in prospective studies of the strong association of the presence of these antibodies with the occurrence of APS events (11, 13, 38).…”

“…IgA anti-B2GP1 has been shown to be strongly associated with DVT and stroke (10) and the thrombogenic effects of IgA anti-β2GP1 antibodies in vitro and in vivo animal models has been shown (11). Along this line our group shown that the presence of IgA anti-B2GP1 was strongly associated with thrombosis in various situations including: thrombosis in hemodialyzed patient (12), graft-thrombosis after kidney transplantation (13), and thrombosis and mortality after heart transplantation (14).…”

Immune Complexes of Beta-2-Glycoprotein I and IgA Antiphospholipid Antibodies Identify Patients With Elevated Risk of Thrombosis and Early Mortality After Heart Transplantation

“…Patients with CDK positive for IgA aB2GP1 who received a kidney transplant showed a greater incidence of early graft loss, mainly due to thrombosis (14,15). This fact has been confirmed in a prospective multicenter study (16).…”

Antiphospholipid antibodies and renal transplant: A systematic review and meta-analysis

“…The diagnosis of allograft thrombosis was consistently biopsy proven (11,14,15,23,(25)(26)(27)(28)(29)(30)(31) and occasionally supported by renal ultrasound or radionuclide scanning before biopsy (18).…”