ABSTRACT
The role of humoral alloreactivity in ABO-compatible liver transplantation remains unclear. To understand the significance of donor-specific HLA alloantibodies (DSA) in liver rejection, we applied the currently used strategy for detection of antibody-mediated rejection of other solid allografts. For this purpose we reviewed the data on 43 recipients of ABO identical/compatible donor livers who had indication liver biopsy stained for complement element C4d and contemporaneous circulating DSA determination. Seventeen (40%) patients had significant circulating DSA in association with diffuse portal C4d deposition (DSA+/diffuse C4d+). These DSA+/diffuse C4d+ subjects had higher frequency of acute cellular rejection (ACR) 15/17 versus 13/26 (88% vs. 50%), p = 0.02, and steroid resistant rejection 7/17 versus 5/26 (41% vs. 19%), p = 0.03. Based on detection of the combination DSA+/diffuse C4d+, 53.6% of cases of ACR had evidence of concurrent humoral alloreactivity. Six of the 10 patients with ductopenic rejection had circulating DSA and diffuse portal C4d, three of whom (2 early and 1 late posttransplantation) developed unrelenting cholestasis, necessitating specific antibody-depleting therapy to salvage the allografts. Thus, in ABO-compatible liver transplantation humoral alloreactivity mediated by antibodies against donor HLA molecules appears to be frequently intertwined with cellular mechanisms of rejection, and to play a role in ductopenia development.
Subject(s)
ABO Blood-Group System/immunology , Bile Duct Diseases/etiology , Graft Rejection/immunology , Histocompatibility Antigens Class I/immunology , Isoantibodies/blood , Liver Transplantation/immunology , Tissue Donors , Adolescent , Adult , Aged , Bile Duct Diseases/pathology , Complement C4b/immunology , Complement C4b/metabolism , Female , Flow Cytometry , Humans , Liver Transplantation/mortality , Male , Middle Aged , Peptide Fragments/immunology , Peptide Fragments/metabolism , Risk Factors , Transplantation, Homologous/immunology , Treatment Outcome , Young AdultABSTRACT
A sensitive spectrophotometric method is reported for the quantitative determination of pentaerythritol tetranitrate in tablets. The method is based on reduction of pentaerythritol tetranitrate with zinc and calcium chloride, and reaction of the nitroso compound thus formed with 1-naphthylamine in acidic medium. The reaction gives a purple product having an absorbance maximum at 545 nm. Beer's law is obeyed in the concentration range of 1-10 micrograms/mL of reaction mixture. The presence of meprobamate in tablets does not interfere with the proposed analytical determination.