C4d-negative antibody-mediated rejection with high anti-angiotensin II type I receptor antibodies in absence of donor-specific antibodies.
OBJECTIVE
Acute antibody-mediated rejection can occur in absence of circulating donor-specific antibodies. Agonistic antibodies targeting the anti-angiotensin II type 1 receptor (anti-AT1 R) are emerging as important non-human leucocyte antigen (HLA) antibodies. Elevated levels of anti-angiotensin II receptor antibodies were first observed in kidney transplant recipients with malignant hypertension and allograft rejection. They have now been studied in three separate kidney transplant populations and associate to frequency of rejection, severity of rejection and graft failure.


METHODS
We report 11 cases of biopsy-proven, Complement 4 fragment d (C4d)-negative, acute rejection occurring without circulating donor-specific anti-HLA antibodies. In eight cases, anti-angiotensin receptor antibodies were retrospectively examined. The remaining three subjects were identified from our centre's newly instituted routine anti-angiotensin receptor antibody screening.


RESULTS
All subjects fulfilled Banff 2013 criteria for antibody-mediated rejection and all responded to anti-rejection therapy, which included plasma exchange and angiotensin receptor blocker therapy.


CONCLUSIONS
These cases support the routine assessment of anti-AT1 R antibodies in kidney transplant recipients to identify subjects at risk. Further studies will need to determine optimal assessment protocol and the effectiveness of pre-emptive treatment with angiotensin receptor blockers.
The Centre for Clinical and Experimental Transplantation (CCET), Central Northern Adelaide Renal and Transplantation Services (CNARTS), Adelaide, South Australia, Australia.|Department of Medicine, The University of Adelaide, Adelaide, South Australia, Australia.
Alexander
A
Fuss
The Centre for Clinical and Experimental Transplantation (CCET), Central Northern Adelaide Renal and Transplantation Services (CNARTS), Adelaide, South Australia, Australia.|Department of Medicine, The University of Adelaide, Adelaide, South Australia, Australia.
Christopher M
CM
Hope
Adelaide Division, Australian Red Cross Blood Service (ARCBS), Adelaide, South Australia, Australia.
Susan
S
Deayton
Adelaide Division, Australian Red Cross Blood Service (ARCBS), Adelaide, South Australia, Australia.
Greg Donald
GD
Bennett
Adelaide Division, Australian Red Cross Blood Service (ARCBS), Adelaide, South Australia, Australia.
Rhonda
R
Holdsworth
The Centre for Clinical and Experimental Transplantation (CCET), Central Northern Adelaide Renal and Transplantation Services (CNARTS), Adelaide, South Australia, Australia.|Department of Medicine, The University of Adelaide, Adelaide, South Australia, Australia.
Robert P
RP
Carroll
The Centre for Clinical and Experimental Transplantation (CCET), Central Northern Adelaide Renal and Transplantation Services (CNARTS), Adelaide, South Australia, Australia.|Department of Medicine, The University of Adelaide, Adelaide, South Australia, Australia.
P Toby H
PT
Coates
D000328:Adult; D000368:Aged; D000906:Antibodies / Q000097:blood / Q000276:immunology*; D015704:CD4 Antigens; D005260:Female; D006084:Graft Rejection / Q000097:blood / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D044140:Receptor, Angiotensin, Type 1 / Q000276:immunology*; D012189:Retrospective Studies; D014019:Tissue Donors
D000906:Antibodies; D015704:CD4 Antigens; D044140:Receptor, Angiotensin, Type 1
AT1R; angiotensin II type 1 receptor; angiotensin receptor blocker; antibody; antibody-mediated rejection; atypical HLA antibody