Pre-existing Ab against vimentin leads to false-positive HLA Ab results in two pediatric heart transplant candidates.

ABSTRACT

BACKGROUND: HLA Ab analysis is carried out as a routine assay both pre- and post-heart transplantation to identify Abs directed against HLA with a focus post-transplant on those Abs that are donor-specific. While virtual crossmatching has decreased the requirement for prospective crossmatching in many cases, the management of highly sensitized children on the heart transplant waitlist remains challenging and can delay the ability to successfully identify a suitable organ. METHODS: This report describes the histocompatibility assessment and management of identical twin boys with familial restrictive cardiomyopathy serially listed for transplant. The boys presented with HLA Ab testing that demonstrated broad pan-DR reactivity which included Abs directed against SAgs. RESULTS: Our team began investigating the initial Ab results soon after listing the first child; the brother was listed 8 days later and had the same broad Ab profile. The clinical lab ran multiple investigative crossmatches using donor samples with known antigen typing and continued to see broad reactivity. We then partnered with an affiliated research lab where we identified high-level Abs directed against vimentin along with vimentin-positive exosomes in both boys. CONCLUSIONS: While Abs directed against the self-antigen vimentin has been described to cause false-positive tissue crossmatches, this is the first report of these Abs being associated with false-positive Ab screens using solid-phase assays. This finding informed our management and surveillance in these two vulnerable pediatric heart transplant candidates.