Kidney transplant outcomes in patients with antibodies to human neutrophil antigen 3a.

BACKGROUND: Antibody mediated rejection (ABMR) of kidney transplants has been shown to occur in the absence of a known donor specific antibody to human leucocyte antigen (HLA). Antibodies to the human neutrophil antigen (HNA) system have been detected in kidney transplant recipients and linked to ABMR in the absence of an HLA donor specific antibody (DSA), but there remains limited literature regarding this. METHODS: Case series analysis was carried out examining three cases of HNA-3a antibody positive flow cytometry cross match (FC-XM) from two transplant centres in Scotland. RESULTS: All patients included were female and had been sensitised as a result of pregnancy. One live donor recipient with HNA-3a antibodies identified prior to transplant received ATG induction and has had a good outcome. The remaining two patients received deceased donor transplants. HNA-3a antibodies were indicated following a retrospective flow cytometry crossmatch. Both patients received Basiliximab induction and both have experienced ABMR requiring supplementary immunosuppression. CONCLUSIONS: The predicted rate of HNA-3a antibodies amongst patients awaiting kidney transplant in the UK is <1%. However, with increasing evidence to support a role for HNA-3a antibodies in the development of ABMR there may be value in screening at risk groups to allow for augmented immunosuppression to be considered at the time of kidney transplant.

Comparison of kidney transplant outcomes in HLA compatible and incompatible transplantation: A national cohort study.

BACKGROUND: Reports of HLA incompatible (HLAi) kidney transplant outcomes are inconclusive, especially in the context of lower level Donor Specific Antibodies (DSA). METHODS: Multi-centre national cohort study of HLAi kidney transplant recipients matched in 1:2 ratio with HLA compatible (HLAc) kidney transplant recipients. HLAi defined as DSA identified by Luminex. Antibody mediated rejection (AMR) and transplant-survival were analysed using Kaplan-Meier plots. Propensity score (PS) matching was used to compare recipient and transplant survival between groups. RESULTS: We included 61 HLAi and 122 HLAc recipients; mean age 46 years; 60% female. MFIT0 : 3327 (IQR 1352-6458), 23 (38%) were Flow cytometry crossmatch positive (FC-XMPOS ). DSAPOS /FC-XMPOS transplantation carried an increased risk of AMR at 1 year (52%) compared to DSAPOS /FC-XMNEG (27%) and HLAc (0%). Unadjusted death censored graft loss at 3 years was 13% (HLAi) and 8% (HLAc). Three-year patient survival was 95% in HLAc, 84% in DSAPOS /FC-XMNEG and 69% in DSAPOS /FC-XMPOS recipients; 58% of HLAi deaths were infection-related. HLA incompatibility was associated with a decreased 3-year survival in our PS-matched cohort. CONCLUSION: In kidney transplantation, DSA and positive FC-XM carries an increased risk of AMR. Despite inferior transplant and survival outcomes compared to HLAc transplantation, it remains a realistic option for highly sensitized patients facing prolonged waiting times and reduced survival on dialysis.

Highly sensitised patients awaiting deceased donor renal transplants are disadvantaged by the presence of denatured HLA antibody detected in routine HLA antibody testing.

Luminex single antigen bead (SAB) assays used to detect HLA antibodies may artificially increase sensitisation in highly sensitised patients (HSP). The presence of denatured HLA (dHLA) within the assay enables antibodies specific to cryptic HLA epitopes to bind, such antibodies are not clinically relevant. We sought to exclude dHLA reactivity in a cohort of very HSP, calculated reaction frequency (cRF) 95%-100% and determine the effect upon sensitisation. Such patients have limited access to suitable donors and small changes in their HLA antibody profile, particularly where their cRF is 100%, can increase their opportunity of a transplant. We determined the presence of dHLA by aligning antibody reactivity which did not correspond to known HLA class I epitope mismatches with the results of assays modified to detect class I dHLA. 130 class I dHLA reactions were identified within 11 HSP, all of whom had clear sensitising events. cRF was corrected for dHLA, mean cRF 98.2% (93-100) pre and 95.5% (87-100) post correction (p = 0.0156). An increase in the number of predicted compatible donors (p = 0.0078) after dHLA correction was demonstrated. Two manufacturers SAB assays were used. A reduction of patients with 100% cRF was observed for both manufactures. dHLA is contributing to sensitisation in HSP and is detrimental to their chances of receiving a compatible transplant. The observed dHLA reactivity varied according to kit manufacturers (p = 0.0001), this is potentially a useful finding for laboratories wishing to discriminate between nHLA and dHLA, but without the resources required to regularly perform dHLA assay and epitope analyses.