Update on diagnostic and therapeutic strategies for antibody-mediated rejection in kidney transplantation

Table 2 Antibody-mediated rejection spectrum according to Banff 2019 classification report

Criterion	Active AMR	Chronic active AMR	Chronic (inactive) AMR
Criterion 1: Histopathology	Acute tissue injury, including one or more of the following: (1) MIV (glomerulitis and/or ptc) in the absence of recurrent or de-novo GN, intimal or transmural arteritis; (2) Acute TMA, in the absence of any other apparent cause; and (3) ATI, in the absence of any other apparent cause	Chronic tissue injury, including one or more of the following: (1) TG (GBM duplication in the absence of subendothelial immune complex deposits) if no evidence of chronic TMA in the absence of recurrent or de-novo glomerulonephritis; (2) Severe peritubular capillary basement membrane multilayering (requires EM); and (3) Transplant arteriopathy (arterial intimal fibrosis of new onset) and mild to moderate acute tissue injury (MIV)	Chronic tissue injury: (1) TG, and/or severe ptc basement membrane multilayering (requires EM) without MVI; and (2) Significant loss of ptc (capillaries simply no longer exist to show capillaritis)
Criterion 2: Evidence of antibody interaction with the endothelium	These include at least one of the following: (1) C4d deposition in ptc, OR; (2) At least moderate MIV, OR; and (3) Increased expression of gene transcripts/classifiers in the biopsy tissue	C4d deposition in ptc, or at least moderate MIV, or increased expression of gene transcripts/classifiers in the biopsy tissue	C4d negative
			There may be prior evidence of antibody interaction with the endothelium
Criterion 3: Serologic evidence of DSAs (HLA or other antigens)	Detectable serum anti-HLA DSA	Detectable serum anti-HLA DSA	Anti-HLA DSA may be undetectable
	If anti-HLA DSA is undetectable, non-HLA antibody testing	If anti-HLA DSA is undetectable, non-HLA antibody testing	However, there should be prior evidence of anti-HLA or non-HLA DSA
	C4d staining or expression of validated transcripts/classifiers may substitute for DSA	C4d staining or expression of validated transcripts/classifiers may substitute for DSA

AMR: Antibody-mediated rejection; ptc: Peritubular capillary; GN: Glomerulonephritis; TMA: Thrombotic microangiopathy; ATI: Acute tubular injury; TG: Transplant glomeruopathy; GBM: Glomerular basement membrane; EM: Electron microscope; HLA: Human leukocyte antigen; DSA: Donor-specific antibody; MVI: Microvascular inflammation.