ABSTRACT
The majority of de novo donor specific HLA antibodies (DSAs) in transplant patients are directed to HLA-DQ antigens, which consist of a heterodimer of alpha and beta chains. Although a heterodimer can theoretically be cis- or trans-encoded, the sensitizing forms generally appear to be forms. DSA to DQ trans-heterodimer has never been reported. We reviewed 360 post-kidney transplant recipients (transplant: 2002-2013; follow-up: 5.6±3.3years). DQ DSA was detected in 46 of 57 patients who developed DSA. DSA specificity was consistent with donor mismatched DQ trans-heterodimers in three patients: DQ2.5 (DQB1*02, DQA1*05), DQ2.3 (DQB1*02, DQA1*03), and DQ4.3 (DQB1*04, DQA1*03). Two of them eventually lost grafts (2 and 5years later) with allograft nephropathy. In conclusion, post-transplant patients may develop DSA to donor DQ trans-heterodimers. Further studies are warranted to determine the clinical significance of such DSAs.
Subject(s)
Antibody Specificity/immunology , HLA-DQ Antigens/immunology , Isoantibodies/immunology , Adolescent , Adult , Aged , Alleles , Child , Child, Preschool , Female , Graft Rejection/genetics , Graft Rejection/immunology , Graft Survival/genetics , Graft Survival/immunology , HLA Antigens/chemistry , HLA Antigens/genetics , HLA Antigens/immunology , HLA-DQ Antigens/chemistry , HLA-DQ Antigens/genetics , Humans , Kidney Transplantation , Male , Middle Aged , Patient Outcome Assessment , Protein Multimerization , Retrospective Studies , Tissue Donors , Young AdultABSTRACT
A positive crossmatch has been associated with increased risk in liver transplantation. To study the clinical significance of preformed donor-specific human leukocyte antigen antibodies (DSAs) in liver transplantation, we reviewed patients who underwent liver transplantation with a strongly positive flow cytometry crossmatch. DSAs were evaluated with a Luminex solid phase assay. The complement-fixing ability of DSAs was tested with a complement component 1q (C1q) assay. Using an assay correlation between complement-dependent cytotoxicity crossmatch, flow cytometry crossmatch, and DSA results, we reviewed the effects of DSAs on the outcomes of our patients as well as reported cases in the literature. Five of 69 liver recipients had a strongly positive crossmatch: 4 had a positive T cell crossmatch [median channel shift (MCS) = 383.5 ± 38.9], and 5 had a positive B cell crossmatch (MCS = 408.8 ± 52.3). The DSAs were class I only in 1 patient, class I and II in 3 patients, and class II only in 1 patient. Cholestasis, acute rejection, or both were observed in 3 of the 4 patients with a positive T cell crossmatch with an MCS approximately greater than 300. The C1q assay was positive for 3 patients. Two had either persistent cholestasis or early acute rejection. One patient who was treated with preemptive intravenous immunoglobulin had an unremarkable outcome despite a positive C1q result. One of the 2 patients with a negative C1q assay experienced persistent cholestasis and early and recurrent acute rejection; the other had an unremarkable outcome. None of the patients died or lost a graft within the first year of transplantation. Our study suggests that human leukocyte antigen antibody screening, flow cytometry crossmatch MCS levels, DSA mean fluorescent intensity levels, and C1q assays may be useful in assessing the risk of antibody-mediated rejection and timely interventions in liver transplantation.
