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Significance of the total i -score. Michael Mengel Alberta Transplant Applied Genomics Centre University of Alberta, Edmonton, Canada. 0%. 10%. 25%. The Banff-Consensus Lorraine Racusen & Kim Solez. Cellular rejection. Granzyme B. Banff i- and t-score. Do not consider for i-score:

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significance of the total i score

Significance of the total i-score

Michael Mengel

Alberta Transplant Applied Genomics Centre

University of Alberta, Edmonton, Canada

slide2

0%

10%

25%

The Banff-Consensus

Lorraine Racusen & Kim Solez

slide4

Banff i- and t-score

  • Do not consider for i-score:
  • subcapsular infiltrates
  • perivascular infiltrates
  • fibrotic areas
  • areas of tubular atrophy
  • ?nodular infiltrates

Table 4 - Quantitative Criteria for Mononuclear Cell Interstitial Inflammation ("i") Scores

i0 - No or trivial interstitial inflammation

(<10% of unscarred parenchyma)

i1 - 10 to 25% of parenchyma inflamed

i2 - 26 to 50% of parenchyma inflamed

i3 - >50% of parenchyma inflamed

  • Do not consider for t-score:
  • moderately to severe atrophic tubules
  • ?mild atrophic tubules in areas of tubular atrophy and fibrosis
  • ?tubules in areas with minor inflammation

Table 2 - Quantitative Criteria for Tubulitis ("t") Score (applies to tubules no more than mildly atrophic)

t0 - No mononuclear cells in tubules

t1 - Foci with 1 to 4 cells/tubular cross section or

10 tubular cells

t2 - Foci with 5 to 10 cells/tubular cross section

t3 - Foci with >10 cells/tubular cross section, or

the presence of at least two areas of tubular

basement membrane destruction

accompanied by i2/i3 inflammation and t2

tubulitis elsewhere in the biopsy.

Racusen L. et al., Kidney Int. 1999 Feb;55(2):713-23.

infiltrate type
Infiltrate type

p  0.05

Mengel et al. Am J Transplant. 2007 Feb;7(2):356-65.

infiltrates and allograft function
Infiltrates and allograft function

p  0.05

Mengel et al. Am J Transplant. 2007 Feb;7(2):356-65.

infiltrates and outcome
Infiltrates and outcome

Mengel et al. Am J Transplant. 2007 Feb;7(2):356-65.

how much graft inflammation is significant
How much graft inflammation is significant?

normal

fibrosis

fibrosis+ i=1

fibrosis+ i >1

p<0.001

Cosio FG et al AJT, 5:2464, 2005

scoring inflammation in renal allograft biopsies

100% Cortex

nodular

perivascular

absolute scoring

40% i-IFTA

10% i-Banff

5%

5%

3%

3%

subcapsular

25% = Banff i-score 1

“67% i-IFTA”

relative scoring

according to current Banff rules

40% non-scarred

compartment

60% IFTA compartment

Scoring inflammation in renal allograft biopsies
banff i and total i score and diagnosis interstitial infiltrates are not disease specific
Banff i- and total i-score and diagnosis: interstitial infiltrates are not disease specific

*

total i-score

i-score

*p<0.05

*

*

*

% cortex with infiltrate

*

*

the total i score is superior in reflecting the molecular inflammatory burden

p=0.012

p=0.001

p=0.9

p=0.7

AUC

total i-score 0.85

i-score 0.73

AUC

total i-score 0.82

i-score 0.58

AUC

total i-score 0.86

i-score 0.86

AUC

total i-score 0.97

i-score 0.91

The total i-score is superior in reflecting the molecular inflammatory burden

A

B

C

D

t0 cases with high total inflammatory burden have also significantly higher other banff scores
t0-cases with high total inflammatory burden have also significantly higher other Banff scores

*p<0.05

prognostic value of banff i and total i score versus diagnosis
Prognostic value of Banff i- and total i-score versus diagnosis

← increasing ti/i-scores

total i-score

AUC = 0.81

total vs. i-score

p=0.012

i-score

AUC = 0.65

ABMR

TG

TCMR,GN

Borderline

CNIT

Other

ATN

IFTA NOS

banff i and total i score and allograft survival
Banff i- and total i-score and allograft survival

A

C

i-score <25%

i-score <25%

i-score >25%

i-score >25%

i-score

p=0.599

p=0.058

B

D

total i-score <25%

total i-score <25%

total i-score

total i-score >25%

total i-score >25%

p<0.0001

p=0.002

all allografts (n=104)

allografts with ≥IFTA grade I (n=88)

conclusions about new total i score
Conclusions about new total-i-score
  • Comprises primarily two major inflammatory compartments:
    • i-Banff (non-scarred)
    • i-IFTA (scarred)
  • reflects better the molecular burden of inflammation and tissue injury
  • more robust predictor of allograft survival
proposal for total i score
Proposal for total i-score
  • Test reproducibility for i-Banff, i-IFTA, and total i-score:
    • if feasible, reporting of the different inflammatory compartments might allow to design new clinical trials
  • Incorporate into the Banff-classification as a prognostic lesion
    • either as ti-score alone or together with i-Banff and i-IFTA
acknowledgements
Acknowledgements

Kara Allanach

Dina Badr

Sakarn Bunnag

Patricia Campbell

Jessica Chang

Gunilla Einecke

Konrad Famulski

Luis Hidalgo

Anna Hutton

Zija Jacaj

Deborah James

Bruce Kaplan

Bert Kasiske

Nathalie Kayser

Daniel Kayser

Daniel Kim

Rob Leduc

Arthur Matas

Vido Ramassar

Jeff Reeve

Gui Renesto

Joana Sellares

Banu Sis

Lin-Fu Zhu

Stromedix, Astellas

Roche Molecular Systems, Roche Canada

Alberta Health Services

University Hospital Foundation

Roche Organ Transplant Research Foundation

Genome Canada/Genome Alberta

University of Alberta

Alberta Ministry of Advanced Education and Technology

Canada Foundation for Innovation

Canadian Institutes of Health Research

Kidney Foundation of Canada

Alberta Heritage Foundation for Medical Research

Muttart Chair in Clinical Immunology,

Canada Research Chair in Life Sciences

Special thanks to our clinical collaborators

Special thanks to our patients