Antibodies Against ARHGDIB and ARHGDIB Gene Expression Associate With Kidney Allograft Outcome

Transplantation. 2020 Jul;104(7):1462-1471. doi: 10.1097/TP.0000000000003005.


Background: The impact of donor-specific anti-HLA antibodies (DSA) on antibody-mediated rejection (AMR) and kidney allograft failure is well established. However, the relevance of non-HLA antibodies remains unclear.

Methods: We investigated 13 pretransplant non-HLA antibodies and their association with histology of AMR (AMRh) and kidney allograft failure. We included single kidney recipients (n = 203) with AMRh, according to the Banff 2017 classification and matched AMRh-free controls (n = 219). Non-HLA antibodies were assessed using multiplex Luminex assay.

Results: Of the selected non-HLA antibodies (against agrin, adipocyte plasma membrane-associated protein, Rho GDP-dissociation inhibitor 2 [ARHGDIB], Rho guanine nucleotide exchange factor 6, angiotensin-II type 1 receptor, endothelin type A receptor, lamin B1, BPI fold-containing family B member 1, peroxisomal trans-2-enoyl-coenzyme A reductase, phospholipase A2 receptor, protein kinase C zeta type, tubulin beta-4B class IVb, vimentin), only antibodies against ARHGDIB (adjusted median fluorescence intensity [aMFI] ≥ 1000), a minor histocompatibility antigen, associated with graft failure, in univariate and multivariate models (hazard ratio = 2.7; 95% confidence interval [CI],1.3-5.4; P = 0.007). There was a 19.5-fold (95% CI, 6.0-63.9; P < 0.0001) increased risk of graft failure in patients positive for both DSA and anti-ARHGDIB antibodies (aMFI ≥ 1000) versus patients negative for both DSA and anti-ARHGDIB antibodies, compared with a 4.4-fold (95% CI, 2.4-8.2; P < 0.0001) increased risk in patients with only DSA, and a 4.1-fold (95% CI, 1.4-11.7; P = 0.009) increased risk in patients with only anti-ARHGDIB antibodies above 2000 aMFI. AMRh associated with increased intrarenal expression of the ARHGDIB gene. In the absence of AMRh and DSA, anti-ARHGDIB antibodies were not clearly associated with graft failure.

Conclusions: The presence of pretransplant anti-ARHGDIB antibodies has an additive effect in patients with DSA on the risk of graft failure via AMRh. Other investigated non-HLA antibodies, including antibodies against angiotensin-II type 1 receptor, did not contribute to risk stratification and could not explain the histology of AMR in the absence of DSA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Allografts / immunology
  • Allografts / pathology
  • Autoantibodies / blood*
  • Autoantibodies / immunology
  • Autoantigens / immunology
  • Autoantigens / metabolism
  • Biopsy / statistics & numerical data
  • Case-Control Studies
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling / statistics & numerical data
  • Graft Rejection / diagnosis
  • Graft Rejection / epidemiology*
  • Graft Rejection / immunology
  • Graft Rejection / pathology
  • Graft Survival / immunology
  • Histocompatibility Testing / methods
  • Histocompatibility Testing / statistics & numerical data
  • Humans
  • Kidney / immunology
  • Kidney / pathology
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / immunology
  • Kidney Failure, Chronic / surgery*
  • Kidney Transplantation / adverse effects*
  • Male
  • Middle Aged
  • Preoperative Period
  • Prospective Studies
  • Risk Assessment / methods
  • Risk Assessment / statistics & numerical data
  • Transplantation, Homologous / adverse effects
  • rho Guanine Nucleotide Dissociation Inhibitor beta / immunology
  • rho Guanine Nucleotide Dissociation Inhibitor beta / metabolism*


  • ARHGDIB protein, human
  • Autoantibodies
  • Autoantigens
  • rho Guanine Nucleotide Dissociation Inhibitor beta