Active ABMR; all 3 criteria must be met for diagnosis*¶ |
1. Histologic evidence of acute tissue injury, including one or more of the following: |
Microvascular inflammation (g >0Δ and/or ptc >0), in the absence of recurrent or de novo glomerulonephritis, although in the presence of acute TCMR, borderline infiltrate, or infection, ptc ≥1 alone is not sufficient and g must ≥1 |
Intimal or transmural arteritis (v >0)◊ |
Acute TMA, in the absence of any other cause |
Acute tubular injury, in the absence of any other apparent cause |
2. Evidence of current/recent antibody interaction with vascular endothelium, including at least one of the following: |
Linear C4d staining in ptc (C4d2 or C4d3 by IF on frozen sections, or C4d >0 by IHC on paraffin sections) |
At least moderate microvascular inflammation ([g + ptc] ≥2)§ |
Increased expression of gene transcripts/classifiers in the biopsy tissue strongly associated with ABMR, if thoroughly validated¥ |
3. Serologic evidence of DSAs (HLA or other antigens). C4d staining or expression of validated transcripts/classifiers as noted above in criterion 2 may substitute for DSA; however thorough DSA testing, including testing for non-HLA antibodies if HLA antibody testing is negative, is strongly advised whenever criteria 1 and 2 are met. |
Chronic, active ABMR; all 3 criteria must be met for diagnosis*‡ |
1. Morphologic evidence of chronic tissue injury, including 1 or more of the following: |
TG (cg >0)†, if no evidence of chronic TMA or chronic/de novo glomerulonephritis |
Severe ptc basement membrane multilayering (requires EM)** |
Arterial intimal fibrosis of new onset, excluding other causes¶¶ |
2. Evidence of current/recent antibody interaction with vascular endothelium, including at least one of the following: |
Linear C4d staining in ptc (C4d2 or C4d3 by IF on frozen sections, or C4d >0 by IHC on paraffin sections) |
At least moderate microvascular inflammation ([g + ptc] ≥2)§ |
Increased expression of gene transcripts/classifiers in the biopsy tissue strongly associated with ABMR, if thoroughly validated¥ |
3. Serologic evidence of DSAs (HLA or other antigens). C4d staining or expression of validated transcripts/classifiers as noted above in criterion 2 may substitute for DSA; however thorough DSA testing, including testing for non-HLA antibodies if HLA antibody testing is negative, is strongly advised whenever criteria 1 and 2 are met. |
C4d staining without evidence of rejection; all 4 features must be present for diagnosisΔΔ |
1. Linear C4d staining in ptc (C4d2 or C4d3 by IF on frozen sections, or C4d >0 by IHC on paraffin sections) |
2. Criterion 1 for active or chronic, active ABMR not met |
3. No molecular evidence for ABMR as in criterion 2 for active and chronic, active ABMR |
4. No acute or chronic, active TCMR or borderline changes |
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