Potential synergistic role of pre-formed GSTT1 antibodies and de novo HLA antibodies in a heart-transplant recipient diagnosed with AMR.

Our center had a case of a 20-year old female with severe bi-ventricular dysfunction, leading to heart transplantation. Strong GSTT1 antibody was detected pre-transplant, which encouraged us to further study its possible significance. Glutathione S-transferases (GSTs) are a class of enzymes that metabolize xenobiotics. We hypothesized that high-titer non-HLA antibodies to GSTT1 can be generated in recipients who have a complete GSTT1 gene deletion and are exposed to GSTT1 antigen. When a donor organ is transplanted, the anti-GSTT1 antibodies could bind to functional GSTT1 which has been exposed due to transplant-related injury and contribute to allo-rejection. We genotyped GSTT1 with Real-Time PCR along with antibody screening using both HLA and non-HLA panels and found this recipient had a null GSTT1 genotype. Pre-transplant serum showed significantly high GSTT1 antibody. One-year post-transplant, there was an abnormal biopsy with antibody-mediated rejection (AMR) detected by microscopy and molecular profiling, showing both intra-luminal mononuclear cells as well as plasma cells, an atypical infiltrate. There were low levels of de novo DQ8 antibodies within the first year, that rose to moderate levels two years later with accompanying de novo moderate levels of DQ6 antibodies. Following AMR treatment, the GSTT1 Ab level decreased. Follow up testing showed increased inflammation and AMR by molecular profiling at 28 months post-transplant. The patient developed worsening cardiac allograft vasculopathy (CAV) and ultimately required re-transplantation.