Abstract
The role of non-HLA autoantibodies in chronic-active antibody-mediated rejection (c-aABMR) of kidney transplants is largely unknown. In this study, the presence and clinical relevance of non-HLA autoantibodies using a recently developed multiplex Luminex-based assay were investigated. Patients with a kidney allograft biopsy at least 6 months after transplantation with a diagnosis of c-aABMR (n = 36) or no rejection (n = 21) were included. Pre-transplantation sera and sera at time of biopsy were tested for the presence of 14 relevant autoantibodies.A significantly higher signal for autoantibodies against Rho GDP‐dissociation inhibitor 2 (ARHGDIB) was detected in recipients with c-aABMR as compared to recipients with no rejection. However, ARHGDIB autoantibodies did not associate with graft survival. Levels of autoantibodies against angiotensin II type 1-receptor (AT1R) and peroxisomal trans‐2‐enoyl‐CoA reductase (PECR) were increased in recipients with interstitial fibrosis in their kidney biopsy. Only the signal for AT1R autoantibody showed a linear relationship with the degree of interstitial fibrosis and was associated with graft survival.In conclusion, anti-ARHGDIB autoantibodies are increased when c-aABMR is diagnosed but are not associated with graft survival, while higher levels of AT1R autoantibody are specifically associated with the presence of interstitial fibrosis and graft survival.
Highlights
Long-term graft loss of the kidney allograft has changed little in the last decades and improving this outcome is considered an unmet need [1]
The results of this study show that using a multiplex autoantibody assay, the MFI of 3 out of 14 selected target proteins showed a relation with either a diagnosis of c-aABMR or interstitial fibrosis and graft survival
Autoantibodies against ARHGDIB were exclusively increased at time of biopsy in the cases diagnosed with caABMRh while the MFI remained stable in the cases without rejection
Summary
Long-term graft loss of the kidney allograft has changed little in the last decades and improving this outcome is considered an unmet need [1]. Chronic-active antibody mediated rejection (caABMR) is recognized as one of the major causes of graft loss in the long term in recipients of a donor kidney [2,3]. The median time to diagnosis is about 6 years with a broad range between 1 year to 15 years after kidney transplantation [4,5]. Histology essentially shows signs of chronic microvascular inflammation (glomerulitis and peritubular capillaritis) leading to endothelial basal membrane duplication and interstitial fibrosis and tubular atrophy [6]. The presence of serum anti-donor antibodies is believed to be underlying the pathogenesis. A variable degree of complement activation can be shown as C4d deposition along the capillary walls and binding and activation of Fc-receptor
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