Distinctive morphological features of antibody-mediated and T-cell-mediated acute rejection in pancreas allograft biopsies.

Abstract

Two main histopathological types of acute rejection are recognized in solid organ transplantation: T-cell-mediated rejection (TCMR) and antibody-mediated rejection (AMR). In pancreas allografts the contrasting morphological features of these entities have only recently been described.
Acute TCMR is characterized by active septal infiltrates composed predominantly of T cells and often involving veins (venulitis) and ducts (ductitis). Inflammation of the arterial endothelium (intimal arteritis or endarteritis) may be present. Focal or diffuse acinar inflammation (acinitis) is also typical of TCMR. Acute AMR in contrast, is characterized by predominantly macrophagic (± neutrophilic) inflammation, concentrated in, and around the interacinar microvasculature (interacinar inflammation, capillaritis) and typically shows focal or diffuse C4d staining of the interacinar capillaries. Architectural preservation is common in milder forms of AMR, whereas severe or untreated forms lead to extensive vascular injury and secondary parenchymal hemorrhagic necrosis. These morphological features strongly correlate with the presence of circulating donor-specific antibody (DSA)+.
Stereotypical TCMR and AMR, as well as mixed forms of rejection can be confidently diagnosed in pancreas allograft biopsies with the combination of three elements: systematic analysis of the histological features; evaluation of C4d staining; and determination of the DSA status.