Ann Lab Med.  2015 May;35(3):314-320. 10.3343/alm.2015.35.3.214.

Investigation of Serum Angiotensin II Type 1 Receptor Antibodies at the Time of Renal Allograft Rejection

• Lee H
• Kim JI
• Moon IS
• Chung BH
• Yang CW
• Kim Y
• Han K
• Oh EJ

• KMID: 2363203
• DOI: http://doi.org/10.3343/alm.2015.35.3.214

Abstract

BACKGROUND
Angiotensin II type 1 receptor (AT1R) is responsible for cardiovascular effects mediated by angiotensin II. This study aimed to investigate the impact of antibodies directed against AT1R (anti-AT1R) in renal allograft rejection.
METHODS
We evaluated 53 patients who had biopsy-proven rejection including antibody-mediated rejection (AMR) (N=22), T-cell-mediated rejection (TCMR) (N=29), and mixed AMR and TCMR (N=2). Donor specific HLA antibodies (DSA) and anti-AT1Rs were simultaneously determined.
RESULTS
Anti-AT1Rs were detected in 9.4% (5/53) of rejection patients (one with acute AMR, two with chronic active AMR, one with acute TCMR, and one with mixed acute AMR & TCMR). HLA antibodies and DSA were detected in 75.5% (40/53) and 49.1% (26/53) of patients, respectively. There was no significant difference in transplant characteristics between anti-AT1R(+) and anti-AT1R(-) patients except for the association of HLA class-I DSA(+) and anti-AT1R(+). Four of five anti-AT1R(+) patients had DSA and were also found to have AMR. A single anti-AT1R(+)/DSA(-) patient developed acute TCMR. Detection rates of DSA, HLA antibodies, or anti-AT1R were not different between AMR and TCMR. However, DSA(+)/anti-AT1R(+) was more frequently found in AMR than in TCMR (P=0.036). Patients with anti-AT1R showed a greater tendency to develop high-grade rejection as Banff IIA/IIB or AMR.
CONCLUSIONS
The presence of anti-AT1R was significantly associated with HLA class-I DSA in renal allograft rejection patients. Both anti-AT1R and DSA positivity was associated with AMR in patients with renal allograft rejection.

Keyword

Angiotensin II receptor antibodies; Rejection; Renal transplantation; Biopsy

MeSH Terms

Adult
Antibodies/blood
Female
Graft Rejection/*etiology
HLA Antigens/immunology
Humans
Kidney/pathology
Kidney Transplantation/*adverse effects
Male
Middle Aged
Receptor, Angiotensin, Type 1/*immunology
Tissue Donors
Transplantation, Homologous
Antibodies
HLA Antigens
Receptor, Angiotensin, Type 1

Figure

• 

  Fig. 1 Detection rates of serum anti-AT1R, DSA, anti-HLA, and tissue C4d deposition in renal allograft rejection patients with AMR and TCMR. Two patients with AMR and TCMR mixed rejection were categorized as AMR.Abbreviations: anti-AT1R, antibodies directed against AT1R; DSA, donor specific HLA antibodies; AMR, antibody-mediated rejection; TCMR, T-cell-mediated rejection.

• 

  Fig. 2 Median fluorescence intensity values of detected DSA class I and class II were not different between patients with AMR and TCMR. The top and bottom border of the box means 95% confidence interval. The bars below and above the box mean minimum and maximum values, respectively, and horizontal line in the box means median value.Abbreviations: DSA, donor specific HLA antibodies; AMR, antibody-mediated rejection; TCMR, T-cell-mediated rejection.

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