Beyond Histology: Lowering Human Leukocyte Antigen Antibody to Improve Renal Allograft Survival in Acute Rejection

Abstract

In conclusion, failure to significantly reduce antibody levels and prevent new formation was strongly predictive of allograft loss. This observation suggests that the therapeutic intervention that reduces antibody production may prolong graft survival in transplantation.

Acute and chronic antibody-mediated rejection in pediatric kidney transplantation

“…It has been shown that a fast reduction of DSAs results in better graft survival [60,61]. The most important trial studying the treatment of CAMR in children was carried out by Toenshoff and Billing.…”

Utility of HLA Antibody Testing in Kidney Transplantation

“…Late AMR is associated with chronic pathology and worse dysfunction at the time of diagnosis, mixed cellular and humoral features, and subsequently, lower treatment response rates, [132][133][134] but it is notable that DSA MFI does not reliably further stratify those individuals who will respond to treatment from those who will do not. 133 Indeed, in one study, those who responded to treatment had higher antibody level as estimated by MFI than nonresponders.…”

“…133 Indeed, in one study, those who responded to treatment had higher antibody level as estimated by MFI than nonresponders. 135 Others that do report an association of MFI and treatment response 134,136 note wide overlap in MFI ranges between response groups with no clear discriminating thresholds.…”

“…136 However, both late rejections and concomitant resistance to treatment are strongly associated with class II DSA, especially HLA-DQ, antibody specificities. 119,126,[133][134][135]137 C1q Testing Recent studies have indicated that posttransplant complement-fixing DSA (detected by C1q binding in an SAB assay) may confer greater risk to allografts than noncomplement-binding DSA. In a study of 1016 patients, post-transplant C1q +DSA were associated with worse pathology and 5-year graft survival (54%) than C1q2DSA.…”

Antibody-mediated rejection in liver transplantation: Current controversies and future directions

“…Among kidney transplant recipients with biopsyproven antibody-mediated rejection, those who responded to treatment with T cell depletion with or without plasmapheresis had significantly better longterm graft survival than nonresponders. 57 Interestingly, two-thirds of the responders did not receive any therapy aimed directly at reducing circulating antibodies, such as plasmapheresis, and this highlights the role of cellular immunity underlying the clinical diagnosis of antibody-mediated rejection. Similarly, non-HLA IgG autoantibodies, which are detected in liver transplant recipients at a much higher rate in comparison with the general population, respond to steroids or T cell-targeting therapy.…”