Occurrence of Fatal and Nonfatal Adverse Outcomes after Heart Transplantation in Patients with Pretransplant Noncytotoxic HLA Antibodies

Abstract

HLA antibodies (HLA ab) in transplant candidates have been associated with poor outcome. However, clinical relevance of noncytotoxic antibodies after heart transplant (HT) is controversial. By using a Luminex-based HLA screening, we retested pretransplant sera from HT recipients testing negative for cytotoxic HLA ab and for prospective crossmatch. Out of the 173 consecutive patients assayed (52 ± 13y; 16% females; 47% ischemic etiology), 32 (18%) showed pretransplant HLA ab, and 12 (7%) tested positive against both class I and class II HLA. Recipients with any HLA ab had poorer survival than those without (65 ± 9 versus 82 ± 3%; P = 0.02), accounting for a doubled independent mortality risk (P = 0.04). In addition, HLA-ab detection was associated with increased prevalence of early graft failure (35 versus 15%; P = 0.05) and late cellular rejection (29 versus 11%; P = 0.03). Of the subgroup of 37 patients suspected for antibody mediated rejection (AMR), the 9 with pretransplant HLA ab were more likely to display pathological AMR grade 2 (P = 0.04). By an inexpensive, luminex-based, HLA-screening assay, we were able to detect non-cytotoxic HLA ab predicting fatal and nonfatal adverse outcomes after heart transplant. Allocation strategies and desensitization protocols need to be developed and prospectively tested in these patients.

Significance of Anti-HLA Antibodies on Adult and Pediatric Heart Allograft Outcomes

“…The prevalence of allosensitization in heart transplant candidates increased with the introduction of SPA for screening for HLA antibodies ( 11 ) (Table 1 ). Nevertheless, the risk for poor GS has remained a significant finding even in the more sensitive SPA testing era ( 11 , 12 ).…”

“…The prevalence of allosensitization in heart transplant candidates increased with the introduction of SPA for screening for HLA antibodies ( 11 ) (Table 1 ). Nevertheless, the risk for poor GS has remained a significant finding even in the more sensitive SPA testing era ( 11 , 12 ). The presence of non-cytotoxic HLA antibodies identified by SAB was associated with high risk of death, early graft failure, and late cellular- and antibody-mediated rejection; these findings underscore the need for using sensitive Luminex platform SPA to accurately determine the presence of circulating HLA antibodies ( 12 ).…”

Human Leukocyte Antigen Sensitization in Solid Organ Transplantation: A Primer on Terminology, Testing, and Clinical Significance for the Apheresis Practitioner

“…HLA sensitization to donor antigens can occur prior to or after transplantation. Pre‐transplant sensitization has been found in up to 30% kidney , 18% heart , 29% lung , and 20% liver transplant candidates . Post‐transplant, donor specific sensitization occurs in up to 20% kidney, 19% liver, 23% heart, and 14% lung transplants .…”

Novel insights into pretransplant allosensitization in heart transplant recipients in the contemporary era of immunosuppression and rejection surveillance

“…Although several studies evaluated pretransplant HLA antibodies as detected by SPA in heart transplant recipients [9][10][11][12][13][14][15], there is still conflicting evidence regarding their clinical consequences. In most of these studies, routine C4d staining of EMB specimens as a marker of AMR was unavailable [9,10] or performed just in a part of the study group [11][12][13][14], in one study only postmortem [12]. This may have led to underestimated prevalence and inadequate treatment of AMR resulting in increased mortality observed in individuals with preformed DSA [9,10].…”

“…In several studies, C1q binding antibodies correlated with higher incidence of AMR [6][7][8]. However, there is conflicting evidence regarding association between mortality and morbidity of heart transplant recipients and the presence of pretransplant HLA antibodies as assessed by SPA [9][10][11][12][13][14][15]. Similarly, the clinical significance of antibodies directed against major histocompatibility complex class I chain-related antigen A (MICA) is not well understood [16,17].…”