Characteristics of donor-specific anti-HLA antibodies in renal transplant recipients

Abstract

Introduction Antibody-mediated rejection (AMR) is the major complication of renal transplantation that significantly affects the renal allograft survival. Complement fixation mediated through donor specific anti-Human Leukocyte Antigen (HLA) antibodies (DSA) is the hallmark of AMR. Different methods have been developed to detect harmful DSAs. However, not all DSAs have the same detrimental effect, as different antibody characteristics might trigger distinct immune responses. Aim: In the present study, we assessed various biological (timing of appearance, strength and specificity) and functional (IgG subtype and c1q binding ability) characteristics of DSA in renal transplant patients. Methods A total of 315 kidney transplant recipients were accrued for this study and 39 patients with de novo DSA were retrospectively analysed for different DSA characteristics. The analyses were carried out using commercially available SAB assay for IgG determination, C1q assay for complement binding capability and modified SAB assay for IgG subclass determination (One Lambda) Results Important findings of the study were: (1) majority of the DSAs were denovo antibodies ( p = 0.0001); primarily against HLA class II antigen ( p = 0.0005); and typically developed after one year posttransplant ( p = 0.0001). (2) DSA with highest strength were routinely observed against DQB antigens in comparison to other HLA class I and II antigens ( p = 0.006). (3) IgG1 was the predominant IgG subclass (49.4%), followed by IgG3 (24.7%), IgG2 (16%), and IgG4 (9.9%). (4) DSA MFI and the IgG1 subclass were strongly correlated with C1q positivity ( p = 0.01 and p = 0.009, respectively). Conclusion Among the functional characteristics, higher MFI of DSA and IgG1 subclass were strongly correlated with C1q positivity. Among the biological characteristics, the majority of DSAs were against HLA class II antigens and developed frequently after one-year post transplantation. Further studies are needed to investigate the clinical relevance of these biological and functional DSA characteristics in predicting renal allograft outcomes.