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Revised Banff 2017 Classification of Antibody-Mediated Rejection (ABMR) in Renal Allografts

The Banff classification represented the first attempt to formulate an international, consensus based and structured classification system for the diagnosis and categorization of renal allograft biopsy pathology with a particular focus on the development of the morphological criteria for the diagnosis and classification of rejection.
Revised Banff 2017 classification of antibody-mediated rejection (ABMR) and T cell–mediated rejection (TCMR) in renal allografts

Category 1: Normal biopsy or nonspecific changes
Category 2: Antibody-mediated changes

Active ABMR; all 3 criteria must be met for diagnosis
1. Histologic evidence of acute tissue injury, including 1 or more of the following:

  • Microvascular inflammation (g > 0 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 be ≥ 1
  • Intimal or transmural arteritis (v > 0)¹
  • Acute thrombotic microangiopathy, 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 1 or more of the following:

  • Linear C4d staining in peritubular capillaries (C4d2 or C4d3 by IF on frozen sections, or C4d > 0 by IHC on paraffin sections)
  • At least moderate microvascular inflammation ([g + ptc] ≥2) in the absence of recurrent or de novo glomerulonephritis, although in the presence of acute TCMR, borderline infiltrate, or infection, ptc ≥ 2 alone is not sufficient and g must be ≥1
  • Increased expression of gene transcripts/classifiers in the biopsy tissue strongly associated with ABMR, if thoroughly validated

3. Serologic evidence of donor-specific antibodies (DSA to 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 diagnosis²
1. Morphologic evidence of chronic tissue injury, including 1 or more of the following:

  • Transplant glomerulopathy (cg >0) if no evidence of chronic TMA or chronic recurrent/de novo glomerulonephritis; includes changes evident by electron microscopy (EM) alone (cg1a)
  • Severe peritubular capillary basement membrane multilayering (requires EM)³
  • Arterial intimal fibrosis of new onset, excluding other causes; leukocytes within the sclerotic intima favor chronic ABMR if there is no prior history of TCMR, but are not required

2. Identical to criterion 2 for active ABMR, above
3. Identical to criterion 3 for active ABMR, above, including strong recommendation for DSA testing whenever criteria 1 and 2 are met

C4d Staining without Evidence of Rejection; all 4 features must be present for diagnosis§

  1. Linear C4d staining in peritubular capillaries (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

Category 3: Borderline changes
Suspicious (Borderline) for acute TCMR

  • Foci of tubulitis (t > 0) with minor interstitial inflammation (i0 or i1), or moderate-severe interstitial inflammation (i2 or i3) with mild (t1) tubulitis; retaining the i1 threshold for borderline with t > 0 is permitted although this must be made transparent in reports and publications
  • No intimal or transmural arteritis (v = 0)

Category 4: TCMR

Acute TCMR

  • Grade IA Interstitial inflammation involving >25% of nonsclerotic cortical parenchyma (i2 or i3) with moderate tubulitis (t2) involving 1 or more tubules, not including tubules that are severely atrophic¶
  • Grade IB Interstitial inflammation involving >25% of nonsclerotic cortical parenchyma (i2 or i3) with severe tubulitis (t3) involving 1 or more tubules, not including tubules that are severely atrophic
  • Grade IIA1 Mild to moderate intimal arteritis (v1), with or without interstitial inflammation and/or tubulitis
  • Grade IIB1 Severe intimal arteritis (v2), with or without interstitial inflammation
    and/or tubulitis
  • Grade III1 Transmural arteritis and/or arterial fibrinoid necrosis of medial smooth
    muscle with accompanying mononuclear cell intimal arteritis (v3), with or without interstitial inflammation and/or tubulitis

Chronic Active TCMR

  • Grade IA Interstitial inflammation involving >25% of the total cortex (ti score 2 or
    3) and >25% of the sclerotic cortical parenchyma (i-IFTA score 2 or 3) with moderate tubulitis (t2) involving 1 or more tubules, not including severely atrophic tubules; other known causes of i-IFTA should be ruled out
  • Grade IB Interstitial inflammation involving >25% of the total cortex (ti score 2 or
    3) and >25% of the sclerotic cortical parenchyma (i-IFTA score 2 or 3) with severe tubulitis (t3) involving 1 or more tubules, not including severely atrophic tubules; other known causes of i-IFTA should be ruled out
  • Grade II1 Chronic allograft arteriopathy (arterial intimal fibrosis with mononuclear
    cell inflammation in fibrosis and formation of neointima)

¹ It should be noted that these arterial lesions may be indicative of ABMR, TCMR, or mixed ABMR/TCMR. “v” lesions and chronic allograft arteriopathy are only scored in arteries having a continuous media with ≥2 smooth muscle layers.
² Lesions of chronic active ABMR can range from primarily active lesions with early transplant glomerulopathy (TG) evident only by EM (cg1a) to those with advanced TG and other chronic changes in addition to active microvascular inflammation. For biopsy specimens showing TG and/or peritubular capillary basement membrane multilayering in the absence of evidence of current/recent antibody interaction with the endothelium (criterion 2) but with a prior documented diagnosis of active or chronic active ABMR or documented prior evidence of DSA, the term “chronic ABMR” should be applied.
³ Indicates ≥7 layers in 1 cortical peritubular capillary and ≥5 in 2 additional capillaries, avoiding portions cut tangentially.
§ The clinical significance of these findings may be quite different in grafts exposed to anti–blood group antibodies (ABO-incompatible allografts), where they do not appear to be injurious to the graft and may represent accommodation. However, with anti-HLA antibodies, such lesions may progress to chronic ABMR, and more outcome data are needed.
¶ A severely atrophic tubule is defined as one with each of the following 3 features: a diameter <25% of that of unaffected or minimally affected tubules on the biopsy, an undifferentiated-appearing, cuboidal or flattened epithelium, and pronounced wrinkling and/or thickening of the tubular basement membrane.

 

References:

  1. Haas M, Loupy A, Lefaucheur C, Roufosse C, Glotz D, Seron D, Nankivell BJ, Halloran PF, Colvin RB, Akalin E, Alachkar N, Bagnasco S, Bouatou Y, Becker JU, Cornell LD, van Huyen JPD, Gibson IW, Kraus ES, Mannon RB, Naesens M, Nickeleit V, Nickerson P, Segev DL, Singh HK, Stegall M, Randhawa P, Racusen L, Solez K, Mengel M. The Banff 2017 Kidney Meeting Report: Revised diagnostic criteria for chronic active T cell-mediated rejection, antibody-mediated rejection, and prospects for integrative endpoints for next-generation clinical trials. Am J Transplant. 2018 Feb;18(2):293-307. [Medline]
  2. Aubert O, Loupy A, Hidalgo L, Duong van Huyen JP, Higgins S, Viglietti D, Jouven X, Glotz D, Legendre C, Lefaucheur C, Halloran PF. Antibody-Mediated Rejection Due to Preexisting versus De Novo Donor-Specific Antibodies in Kidney Allograft Recipients. J Am Soc Nephrol. 2017 Jun;28(6):1912-1923. [Medline]

 

Created Mar 27, 2018.

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