KIR-HLA class I mismatch could be involved in antibody-mediated rejection of transplanted kidneys

Recent cohort data shows that microvascular inflammation is more commonly present in kidney transplant recipients with inhibitory KIR-HLA class I mismatch and that these participants have shortened graft survival.

The genetic mismatch between natural killer cell immunoglobulin-like receptors (KIRs) and HLA class I molecules has been proposed to be involved in antibody-mediated graft rejection in kidney transplantation. The current study investigated KIR-HLA class I mismatch in a cohort of kidney transplant recipients who did not receive thyroglobulin or rituximab. All recipients underwent KIR genotyping, and all recipients and donors HLA class I genotyping. Per protocol, all graft recipients underwent biopsies at 12- and 36-months following transplant. Microvascular inflammation, composed of glomerulitis and peritubular capillaritis scores was determined for all biopsies. Of all kidney transplant recipients, 23 participants presented with a microvascular inflammation score ≥2 and 57 control participants with a score ≤1 in any biopsy.

Individual mismatch inhibitory KIR-HLA class I interactions did not seem to affect microvascular inflammation scores. However, the proportion of participants with ≥1 inhibitory KIR-HLA class I mismatch was higher in the group with microvascular inflammation scores of ≥2 (73.9%) versus microvascular inflammation scores of ≤1 (50.9%). The participants presenting with microvascular inflammation scores of ≥2 and inhibitory KIR-HLA class I mismatch also showed significantly lower graft survival compared with participants with lower/absent mismatch (P=0.0488). This phenomenon was not observed in patients with activating KIR-HLA class I mismatch. However, overall, more participants with microvascular inflammation scores ≥2 showed total (inhibitory and/or activating) KIR-HLA class I mismatch than participants with low inflammation scores (87% vs 59.7%; P=0.0183). Finally, graft survival was also lower in participants with microvascular inflammation scores of ≥2 and any KIR-HLA class I mismatch (P=0.0278).

“The presence of genetic inhibitory KIR-HLA class I mismatch is more frequent in kidney recipients with microvascular inflammation. Our results support that KIR-HLA class I mismatch favours the development of microvascular inflammation”, concluded Ms Judith Federico-Vega (Hospital del Mar Research Institute, Barcelona, Spain).

1. Federico-Vega J, et al. KIR-HLA-I genetic mismatch and the development of antibody-mediated rejection and microvascular inflammation after renal transplantation. Abstract #2461, ERA 2024, 23–26 May, Stockholm, Sweden.

Medical writing support was provided by Mihai Surducan, PhD.

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Posted on 20 June 202424 June 2024