Defining chronic rejection in vascularized composite allografts - do we have reliable surrogates to look for?

Chronic rejection (CR) is a major threat in the field of vascularized composite tissue allografts (VCAs) as it causes graft dysfunction and usually graft loss. Unfortunately, knowledge of CR in VCA is incomplete because of the limited number of VCA recipients, the heterogeneous nature of VCAs and the short follow-up.

The diagnosis of CR in VCA has relied on clinical and pathological findings. Clinical changes include graft fibrosis, dyschromia and ischemic/necrotic ulcerations. Pathological changes primarily affect allograft vessels and manifest with graft vasculopathy (i.e. myo-intimal proliferation and luminal narrowing of allograft vessels, leading to graft ischemia). Attempts are made to diagnose CR with non- or minimally-invasive techniques, such as imaging studies (ultrasound biomicroscopy, functional magnetic resonance imaging) and serum biomarkers. These techniques provide interesting results and further insight into the mechanisms of CR in VCA.

The diagnosis of CR in VCA still relies mainly on clinicopathological graft alterations; unfortunately, these become overt rather late during the rejection process, when reversal of CR is problematic. More recent, minimally- or non-invasive techniques have provided encouraging results, but their usefulness in the diagnosis of CR requires further studies. These data highlight the paramount importance of CR prevention.