Donor-specific antibodies (DSA) developed after transplantation
Microscopic
• Hyperacute antibody-mediated rejection (AMR)
Fibrin thrombi in portal and central veins and sinusoids
Neutrophilic &/or fibrinoid arteritis
Patchy or massive hemorrhagic hepatocyte necrosis
• Acute AMR (Banff criteria 2016)
Definite (all following 4 criteria required)
– Histologic pattern of injury
– Positive serum DSA
– Diffuse (> 50%) C4d deposition
– Reasonable exclusion of other insults that might cause similar injury
Suspicious (both following criteria required)
– Positive serum DSA
– C4d core + H-score = 3 or 4
Indeterminate (requires following first 2 + 3 or 4)
– C4d-score + H-score ≥ 2
– DSA is not available, equivocal, or negative
– C4d is not available, equivocal, negative
– Coexisting insult might be contributing to similar injury
• Chronic AMR (Banff criteria 2016)
Probable (all following 4 criteria required)
– Histologic pattern of injury
– Recent (< 3 months) positive serum DSA
– At least focal (> 10%) C4d deposition in portal microvasculature
– Reasonable exclusion of other insults that might cause similar injury
Possible
– As above, but C4d is minimal (< 10%) or absent
Hyperacute Antibody-Mediated Rejection This case of hyperacute AMR features massive, panacinar hemorrhagic necrosis. Hemorrhage into portal tracts is evident. Note the lack of significant inflammatory cell infiltrates. Bile duct damage is also seen.
C4d Immunostaining This patient was diagnosed with late-onset acute rejection 10 days prior and was treated for T cell-mediated rejection. His liver enzymes remained elevated, however. This follow-up biopsy shows features of resolving rejection and patchy sinusoidal C4d immunoreactivity suggesting a role for AMR.
Acute Antibody-Mediated Rejection An allograft biopsy performed 36 days after transplantation shows features suggestive of biliary obstruction with ductular reaction . Bile duct injury is also noted . No evidence of biliary obstruction is demonstrated by image studies, however.
C4d Immunostaining Continuous linear C4d immunoreactivity is observed in endothelial cells lining the portal veins and capillaries in nearly every portal tract present in this biopsy. The patient is also DSA(+), confirming the diagnosis of acute AMR.
TERMINOLOGY
Abbreviations
• Antibody-mediated rejection (AMR)
• Donor-specific antibodies (DSA)
Synonyms
• Humoral rejection
Definitions
• Graft dysfunction mediated by antibodies directed against donor antigens
ETIOLOGY/PATHOGENESIS
Preformed Antibodies
• Major ABO blood group isoagglutinins
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is evident. Note the lack of significant inflammatory cell infiltrates. Bile duct damage 
is also seen.
suggesting a role for AMR.
. Bile duct injury is also noted 
. No evidence of biliary obstruction is demonstrated by image studies, however.
and capillaries 
in nearly every portal tract present in this biopsy. The patient is also DSA(+), confirming the diagnosis of acute AMR.
