Anti-glutathione S-transferase T1 antibody-mediated rejection in C4d-positive renal allograft recipients.
BACKGROUND
Chronic humoral rejection is a progressive form of graft injury, with defined diagnostic criteria, the crucial one being the evidence of circulating anti-donor antibodies. These antibodies are mainly directed against human leucocyte antigens (HLA), but other targets have also been described. We previously reported that antibodies against the Glutathione S-transferase T1 (GSTT1) enzyme appear in recipients without the GSTT1 gene who receive a graft from a GSTT1-positive donor. The primary aim of this study was to analyse the role of GSTT1 in cases of antibody-mediated rejection (AMR) in the absence of anti-HLA antibodies. A second objective was to describe the distribution of the GSTT1 enzyme in the human kidney.


METHODS
Four renal biopsies from four renal transplanted patients with declined renal function and circulating anti-donor GSTT1 antibodies were studied for C4d deposits in sections of paraffin-embedded tissue samples. Anti-donor-specific HLA and MICA antibody detection was done with the Luminex platform and anti-GSTT1 antibodies were tested by indirect immunofluorescence on rat tissues and ELISA assay. DNA of the patients was extracted for GSTT1 genotyping.


RESULTS
Four patients with the GSTT1 donor/recipient mismatch developed anti-GSTT1 antibodies 32, 42, 48 and 60 months after the transplant. One patient also had donor-specific anti-HLA antibodies. Their biopsies showed pathologic lesions compatible with chronic antibody-mediated rejection (CAMR), along with positive C4d deposition in peritubular capillaries in three of them, being no valuable in the other case.


CONCLUSIONS
This is the first study reporting an association between the appearance of chronic antibody-mediated renal allograft rejection and the occurrence of de novo production of anti-GSTT1 antibodies, in the absence of anti-HLA donor-specific antibodies. This fact suggests a potential role of the GSTT1 system in anti-graft immune response.
Aguilera
Isabel
I
Immunology Service, Hospital Universitario Virgen del Rocío, Sevilla, Spain. isabel.aguilera.exts@juntadeandalucia.es
Alvarez-Marquez
Antonia
A
Gentil
Miguel Angel
MA
Fernandez-Alonso
Jorge
J
Fijo
Julia
J
Saez
Carmen
C
Wichmann
Ingeborg
I
Nuñez-Roldan
Antonio
A
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000888:Antibodies, Anti-Idiotypic / Q000097:blood / Q000276:immunology*; D001706:Biopsy; D015935:Complement C4b / Q000378:metabolism*; D005500:Follow-Up Studies; D005982:Glutathione Transferase / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D006084:Graft Rejection / Q000276:immunology*; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000473:pathology; D016030:Kidney Transplantation / Q000276:immunology*; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism*; D014184:Transplantation, Homologous / Q000276:immunology
D000888:Antibodies, Anti-Idiotypic; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d; C413545:glutathione S-transferase T1; D005982:Glutathione Transferase