62
11 11 th th Banff Conference Banff Conference on Allograft Pathology on Allograft Pathology Carol F. Farver, MD Carol F. Farver, MD Cleveland Clinic Cleveland Clinic W. Dean Wallace, MD W. Dean Wallace, MD UCLA UCLA Co-Chairs, 11 Co-Chairs, 11 th th Banff Conference-Lung Banff Conference-Lung June 2011 June 2011

11th banff conference lung final

Embed Size (px)

DESCRIPTION

sistema Banff para el reporte anatomopatológico en rechazo del trasplante pulmonar, en biopsia.

Citation preview

1111thth Banff Conference on Banff Conference on Allograft PathologyAllograft Pathology

Carol F. Farver, MDCarol F. Farver, MDCleveland Clinic Cleveland Clinic

W. Dean Wallace, MDW. Dean Wallace, MDUCLAUCLA

Co-Chairs, 11Co-Chairs, 11thth Banff Conference-Lung Banff Conference-LungJune 2011June 2011

Lung Session TopicsLung Session Topics

• Antibody-mediated Rejection Antibody-mediated Rejection

• Infections in Lung TransplantInfections in Lung Transplant

• Non-BOS Graft DysfunctionNon-BOS Graft Dysfunction

• Endothelial Cells in the Lung AllograftEndothelial Cells in the Lung Allograft

Antibody-mediated RejectionAntibody-mediated RejectionLungLung

• ClinicalClinical– Diagnostic criteriaDiagnostic criteria

– Effect on survivalEffect on survival

– Role in etiology of BOSRole in etiology of BOS

CLINICAL FEATURES OF AMR CLINICAL FEATURES OF AMR IN LUNG TRANSPLANTATIONIN LUNG TRANSPLANTATION

Ramsey Hachem, MDRamsey Hachem, MD

June 7, 2011June 7, 2011

Humoral immunityHumoral immunity

• Rejection T-cell mediatedRejection T-cell mediated

• Role for antibodies in rejectionRole for antibodies in rejection– HLA antibodies in lung transplantationHLA antibodies in lung transplantation– AMR in kidney transplantationAMR in kidney transplantation

• AMR in lung transplantation is enigmaticAMR in lung transplantation is enigmatic

• ““In 2006, no histologic features for In 2006, no histologic features for antibody-mediated rejection in the lung antibody-mediated rejection in the lung were agreed upon”were agreed upon”

J Heart Lung Transplant 2007; 26: 1229

HLA antibodiesHLA antibodies

• HLA AB & BOSHLA AB & BOS• AB precede BOSAB precede BOS• AB & lymphocytic AB & lymphocytic

bronchiolitisbronchiolitis• Underscore role of Underscore role of

humoral immunityhumoral immunity

Transplantation 1998; 65: 648Transplantation 1999; 67: 1155J Heart Lung Transplant 2004; 23: 1135Am J Transplant 2005; 5: 131

AMR studyAMR study

• Retrospective cohort study of acute AMRRetrospective cohort study of acute AMR

• Between 1/1/06 & 1/1/11Between 1/1/06 & 1/1/11

• Follow-up through 4/1/11Follow-up through 4/1/11

• AMR diagnosis fulfilling all 4 criteriaAMR diagnosis fulfilling all 4 criteria– DSA, C4d, pathology, & graft dysfunctionDSA, C4d, pathology, & graft dysfunction

• 19 patients19 patients

Donor-specific antibodiesDonor-specific antibodies

19/19 had circulating DSA19/19 had circulating DSA Immunodominant DSA MFIImmunodominant DSA MFI

Neutrophilic pneumonitis: n=10

b

Capillaries injury with pneumonitis: n=9

+C4d staining: n=19

Early outcomesEarly outcomes

• 14/19 (74%) improved & discharged14/19 (74%) improved & discharged– 8/9 (89%) with capillary injury improved8/9 (89%) with capillary injury improved– 6/10 (60%) without capillary injury improved6/10 (60%) without capillary injury improved

• 5/19 ( 26%) did not respond, died of 5/19 ( 26%) did not respond, died of refractory AMRrefractory AMR

DSA clearanceDSA clearance

Time after AMR diagnosis, d

1825146010957303650S

urv

iva

l

1.1

1.0.9

.8

.7

.6

.5

.4

.3

.2

.10.0

Persistent DSA

Cleared DSA

log rank p = 0.005

BOSBOS(Survived AMR: n=14)(Survived AMR: n=14)

• 1 pt: Pre-existing BOS1 pt: Pre-existing BOS

• 8/13 pts: Developed BOS within 1 year of 8/13 pts: Developed BOS within 1 year of AMR diagnosis. AMR diagnosis.

Overall SurvivalOverall Survival(n=19 patients)(n=19 patients)

Time after AMR diagnosis, d

1825146010957303650

Su

rviv

al

1.0

.8

.6

.4

.2

0.0

10/19 (53%) diedAMR, n = 5BOS, n = 4Pneumonia, n = 1

ConclusionsConclusions

• AMR may cause acute graft failureAMR may cause acute graft failure

• Index of suspicionIndex of suspicion

• Less severe cases may be unrecognizedLess severe cases may be unrecognized– ““Subclinical humoral rejection” & potential Subclinical humoral rejection” & potential

impact on BOSimpact on BOS– Unknown incidenceUnknown incidence

• Subsequent BOSSubsequent BOS

Antibody-mediated RejectionAntibody-mediated RejectionLungLung

• ClinicalClinical– Diagnostic criteriaDiagnostic criteria– Effect on survivalEffect on survival– Role in etiology of BOSRole in etiology of BOS

• ImmunologyImmunology– Role of DSARole of DSA– HLA vs non-HLA antibodiesHLA vs non-HLA antibodies

1818

Immunology of AMR in Lung Transplantation

11th Banff Conference | June 7, 2011

Medhat Askar, MD, PhDDirector, Allogen Laboratories, Cleveland Clinic

Associate Professor, Department of SurgeryCleveland Clinic Lerner College of Medicine at

Case Western Reserve University School of Medicine

OutlineOutline

Pre-transplant Immunologic risk Pre-transplant Immunologic risk assessmentassessment

Post-transplant immunological Post-transplant immunological monitoringmonitoringDSADSAC4d C4d

Non-HLA targets for humoral Non-HLA targets for humoral immune responsesimmune responses

RESULTSRESULTSPre-transplant DSAPre-transplant DSA

RESULTSRESULTS

Positive Positive Pre-Tx Pre-Tx DSADSA

Reference Reference GroupGroup

PP ValueValue

ACR (≥ ISHLT ACR (≥ ISHLT grade II)grade II)

43%43% 29%29% 0.00090.0009

ACR/100 Pt./YrACR/100 Pt./Yr 20.620.6 7.77.7

(+)Post-Tx DSA with (+) C4d(+)Post-Tx DSA with (+) C4d

>1000 consecutive lung transplant >1000 consecutive lung transplant biopsies at CCF were stained for C4d biopsies at CCF were stained for C4d and C3d (IF)and C3d (IF)Surveillance and Clinical indicationSurveillance and Clinical indication

Four (4) were + C4dFour (4) were + C4dAll in the setting of clinical diseaseAll in the setting of clinical diseaseAcute and organizing DAD (x3); Capillary Acute and organizing DAD (x3); Capillary

injury (x1)injury (x1)

All 4 were + DSA (post-transplant)All 4 were + DSA (post-transplant)None were + C3dNone were + C3d

Pos C4d

Pos C4d

Pos C4d

Non-HLA AntibodiesNon-HLA Antibodies

MHC Class I-related chain A MHC Class I-related chain A (MICA) Antibodies(MICA) Antibodies

6/116 (5%)Reference were Pos for MICA 6/116 (5%)Reference were Pos for MICA AbAb

4/35 (11%) patients with Pos DSA were 4/35 (11%) patients with Pos DSA were also pos for MICA Abalso pos for MICA Ab

None were DSA MICANone were DSA MICA

Antibody-mediated RejectionAntibody-mediated RejectionLungLung

• ClinicalClinical– Diagnostic criteriaDiagnostic criteria– Effect on survivalEffect on survival– Role in etiology of BOSRole in etiology of BOS

• ImmunologyImmunology– Role of DSARole of DSA– HLA vs non-HLA antibodiesHLA vs non-HLA antibodies

• PathologyPathology– Importance of C4d stainingImportance of C4d staining– Pathologic pattern of injuryPathologic pattern of injury

W. Dean Wallace, M.D.W. Dean Wallace, M.D.Associate Professor of PathologyAssociate Professor of PathologyDavid Geffen School of MedicineDavid Geffen School of Medicine

UCLA Medical CenterUCLA Medical Center

Pathology of Antibody-Pathology of Antibody-Mediated Rejection of the Lung Mediated Rejection of the Lung

AllograftAllograft

Putative Stages of Humoral Response to Putative Stages of Humoral Response to an Organ Graft – 2003 NIH an Organ Graft – 2003 NIH recommendationsrecommendations

I: Latent humoral responseI: Latent humoral responseCirculating antibody alone (but without biopsy findings or Circulating antibody alone (but without biopsy findings or graft dysfunction)graft dysfunction)

II: Silent humoral reactionII: Silent humoral reaction (accommodation vs pre-rejection (accommodation vs pre-rejection state)state)Circulating antibody, C4d deposition (but without histologic Circulating antibody, C4d deposition (but without histologic changes or graft dysfunction)changes or graft dysfunction)

III: Sub-clinical humoral rejectionIII: Sub-clinical humoral rejectionCirculating antibody, C4d deposition, tissue pathology (but Circulating antibody, C4d deposition, tissue pathology (but without graft dysfunction)without graft dysfunction)

IV: Humoral rejectionIV: Humoral rejectionCirculating antibody, C4d deposition, tissue pathology, Circulating antibody, C4d deposition, tissue pathology, graft dysfunctiongraft dysfunction

Takemoto SK, et al. National conference to assess antibody-mediated rejection in solid organ transplantation. Am J Transplant 2004;4:1033–41.

Complement deposition – ISHLT Complement deposition – ISHLT Lung Rejection Study GroupLung Rejection Study Group

• Historically associated with hyperacute rejection.Historically associated with hyperacute rejection.• Serum anti-HLA antibodies and complement deposition Serum anti-HLA antibodies and complement deposition

support the concept of AMR in the lung.support the concept of AMR in the lung.• Some of the suggested clinical-pathologic features of Some of the suggested clinical-pathologic features of

AMR, extrapolated from findings in other organ allografts AMR, extrapolated from findings in other organ allografts including deposition of C3d and C4d, may serve as a including deposition of C3d and C4d, may serve as a marker AMR.marker AMR.

• Low specificity limits use in protocol biopsies.Low specificity limits use in protocol biopsies.

Stewart S, et al. Revision of the 1996 working formulation….lung rejection. J Heart Lung Transplant 2007; 26:1229-42.

C4d staining in lung transplant C4d staining in lung transplant biopsiesbiopsies

• Saint Martin (1996)Saint Martin (1996)– C3, IgM, IgGC3, IgM, IgG

• Magro (2003)Magro (2003)– +C4d with septal injury+C4d with septal injury– 22 pts with (-) PRA22 pts with (-) PRA

• Magro (2003)Magro (2003)– +C4d with septal injury+C4d with septal injury– 25 lung pts. With (-) PRA, (-) HLA-Abs25 lung pts. With (-) PRA, (-) HLA-Abs

• Magro (2003)Magro (2003)– +C4d with bronchial epithelial injury+C4d with bronchial epithelial injury

• Girnita Al, (2006)Girnita Al, (2006)– 2 pts.2 pts.– +DSA, +C4d+DSA, +C4d

• Wallace (2005)Wallace (2005)– +C4d +C4d

• Hachem et al (unpublished)Hachem et al (unpublished)– C4d+C4d+– 19 lung tx pts.19 lung tx pts.

Post capillary venule

Nonspecific background staining

Nonspecific C4d staining

Nonspecific C4d stainingNonspecific C4d staining

Nonspecific elastic staining

Hyaline membranes in DAD

Capillaritis in transplant patient

with acute pneumonia

the transbronchial biopsy…the transbronchial biopsy…

• ISHLT study group recommends 5 pieces of alveolar ISHLT study group recommends 5 pieces of alveolar tissuetissue

• Unlike in the kidney, heart and liver, lung biopsies are Unlike in the kidney, heart and liver, lung biopsies are very easily crushed and distorted.very easily crushed and distorted.

• Biopsies are frequently inadequate.Biopsies are frequently inadequate.• Procedural hemorrhage can make the biopsy technically Procedural hemorrhage can make the biopsy technically

difficult to perform and interpret.difficult to perform and interpret.• Distinction between normal, infection, aspiration and Distinction between normal, infection, aspiration and

alloimmune rejection can be very difficult. alloimmune rejection can be very difficult.

Putative Stages of Humoral Response to Putative Stages of Humoral Response to an Organ Graft – 2003 NIH an Organ Graft – 2003 NIH recommendationsrecommendations

I: Latent humoral responseI: Latent humoral responseCirculating antibody alone (without biopsy findings or graft Circulating antibody alone (without biopsy findings or graft dysfunction)dysfunction)

II: Silent humoral reactionII: Silent humoral reaction (accommodation vs pre-rejection (accommodation vs pre-rejection state)state)Circulating antibody, (without histologic Circulating antibody, (without histologic changes or graft dysfunction)changes or graft dysfunction)

III: Sub-clinical humoral rejectionIII: Sub-clinical humoral rejectionCirculating antibody, tissue pathology Circulating antibody, tissue pathology (without graft dysfunction)(without graft dysfunction)

IV: Humoral rejectionIV: Humoral rejectionCirculating antibody, tissue pathology, graft Circulating antibody, tissue pathology, graft dysfunctiondysfunction

Takemoto SK, et al. National conference to assess antibody-mediated rejection in solid organ transplantation. Am J Transplant 2004;4:1033–41.

C4d C4d depositiondeposition

C4d C4d deposition,deposition,

C4d C4d deposition,deposition,

Putative Stages of Humoral Response to Putative Stages of Humoral Response to an Organ Graft – 2003 NIH an Organ Graft – 2003 NIH recommendationsrecommendations

I: Latent humoral response/Silent humoral reactionI: Latent humoral response/Silent humoral reaction Circulating antibody alone (without biopsy findings or graft Circulating antibody alone (without biopsy findings or graft dysfunction)dysfunction)

III: Sub-clinical humoral rejectionIII: Sub-clinical humoral rejectionCirculating antibody, (without graft Circulating antibody, (without graft dysfunction)dysfunction)

IV: Humoral rejectionIV: Humoral rejectionCirculating antibody, graft dysfunctionCirculating antibody, graft dysfunction

tissue pathologytissue pathology

tissue pathology,tissue pathology,

I: Latent humoral response/Silent humoral reaction/Sub-I: Latent humoral response/Silent humoral reaction/Sub-clinical humoral rejectionclinical humoral rejectionCirculating antibody alone (without biopsy findings or Circulating antibody alone (without biopsy findings or graft dysfunction)graft dysfunction)

II: Humoral rejectionII: Humoral rejectionCirculating antibody, graft dysfunctionCirculating antibody, graft dysfunction

Where is the pathologist?

Clinical-Pathologic Diagnosis of Clinical-Pathologic Diagnosis of AMR in the Lung AllograftAMR in the Lung Allograft

• ObjectiveObjective– Determine if there is a specific histopathologic or Determine if there is a specific histopathologic or

immunohistochemical finding that is characteristic of immunohistochemical finding that is characteristic of patients with de-novo DSA and AMR.patients with de-novo DSA and AMR.

• Criteria for AMRCriteria for AMR– Detection of circulating DSADetection of circulating DSA– Compatible tissue pathologyCompatible tissue pathology

• Intravascular neutrophilsIntravascular neutrophils• C3d/C4d deposition?C3d/C4d deposition?

– Graft dysfunctionGraft dysfunction

Matt DeNicola, Sam Weigt, W. Dean Wallace. UCLA David Geffen School of Medicine

Study designStudy design

• Case control study:Case control study:– Since 1/1/2006, lung txp recipients screened Since 1/1/2006, lung txp recipients screened

for DSA at surveillance time-points.for DSA at surveillance time-points.– Inclusion required Tbbx within 30 days of de-Inclusion required Tbbx within 30 days of de-

novo DSA or negative screening test for DSA: novo DSA or negative screening test for DSA: • 16 cases with de-novo anti-HLA DSA16 cases with de-novo anti-HLA DSA • 30 controls never developing DSA – bx selected to 30 controls never developing DSA – bx selected to

achieve a similar range of duration post-transplantachieve a similar range of duration post-transplant– 9 with de-novo anti-HLA, not donor specific (Non-DSA) 9 with de-novo anti-HLA, not donor specific (Non-DSA) – 21 without any anti-HLA ab21 without any anti-HLA ab

Study DesignStudy Design

• Biopsies assessed by pathologist blind to any clinical Biopsies assessed by pathologist blind to any clinical data including the presence or absence of DSA.data including the presence or absence of DSA.– Capillary neutrophilia graded on 0-4 scaleCapillary neutrophilia graded on 0-4 scale

• 0 Normal0 Normal• 1+ Mild increase in PMN1+ Mild increase in PMN• 2+ Increase of PMNs with groups of 2 2+ Increase of PMNs with groups of 2 • 3+ Increase of PMNs with groups of 3 or more3+ Increase of PMNs with groups of 3 or more• 4+ Capillaritis 4+ Capillaritis

– DADDAD– Pathology suspicious for AMR was defined as Pathology suspicious for AMR was defined as >> 2+ neutrophilia, 2+ neutrophilia,

or “unexplained” DAD.or “unexplained” DAD.• Biopsies also stained for C4d and C3d and scored by Biopsies also stained for C4d and C3d and scored by

pathologistpathologist– Any positive staining was used for correlation analysesAny positive staining was used for correlation analyses

2+ capillary neutrophilia

C4d

C4d does not correlate with pathology C4d does not correlate with pathology

C4

D c

od

ed

neg

pos

19

47.50

63.33

70.37

8

20.00

80.00

29.63

11

27.50

36.67

84.62

2

5.00

20.00

15.38

27

67.50

13

32.50

30

75.00

10

25.00

40

Suspect AMR (path)

Count

Total %

Col %

Row %

no yes

Left

Right

2-Tail

Fisher's

Exact Test

0.2861

0.9182

0.4507

Prob

Prob(Suspect AMR (path)=yes) is greater for C4D coded=neg than pos

Prob(Suspect AMR (path)=yes) is greater for C4D coded=pos than neg

Prob(Suspect AMR (path)=yes) is different across C4D coded

Alternative Hypothesis

Pathology does correlate with DSAPathology does correlate with DSA

Su

spe

ct A

MR

(p

ath

) no

yes

6

13.04

37.50

18.75

26

56.52

86.67

81.25

10

21.74

62.50

71.43

4

8.70

13.33

28.57

32

69.57

14

30.43

16

34.78

30

65.22

46

DSA

Count

Total %

Col %

Row %

DSA negative

Left

Right

2-Tail

Fisher's

Exact Test

0.0010*

0.9999

0.0016*

Prob

Prob(DSA=negative) is greater for Suspect AMR (path)=no than yes

Prob(DSA=negative) is greater for Suspect AMR (path)=yes than no

Prob(DSA=negative) is different across Suspect AMR (path)

Alternative Hypothesis

Pathology is associated with lung Pathology is associated with lung allograft survivalallograft survival

0 365 730 1095 1460 18250

20

40

60

80

100

2+ Neutrophilia

Log-Rank p = 0.02

Days Post-Transplant

Per

cen

t su

rviv

al

Pathology + DSA is associated with lung Pathology + DSA is associated with lung allograft survivalallograft survival

0 365 730 1095 1460 18250

20

40

60

80

100

Histopathology + DSA

Log-Rank p = 0.02

Days Post-Transplant

Per

cen

t su

rviv

al

Suspected AMR (Pathology + DSA + Suspected AMR (Pathology + DSA + dysfunction) is associated with lung dysfunction) is associated with lung

allograft survivalallograft survival

0 365 730 1095 1460 18250

20

40

60

80

100

Suspected AMR

Log-Rank p = 0.04

Days Post-Transplant

Per

cen

t su

rviv

al

Wallace Pathology SummmaryWallace Pathology Summmary

Pathology may be graded capillary injury Pathology may be graded capillary injury with capillaritis at one end of spectrumwith capillaritis at one end of spectrum

Capillary neutrophils (Capillary neutrophils (>>Grade +2) Grade +2) correlate with post-tx DSA, but not with correlate with post-tx DSA, but not with +C4d+C4d

Almost all biopsiesAlmost all biopsies can demonstrate some form can demonstrate some form of C4d staining; therefore, C4d deposition is of C4d staining; therefore, C4d deposition is nonspecific and is probably not sensitivenonspecific and is probably not sensitive

All features are nonspecific in isolationAll features are nonspecific in isolation

1111thth Banff Conference---Lung Banff Conference---Lung Session Discussion PointsSession Discussion Points

• DSA antibodiesDSA antibodies– Pre-transplant (memory) Abs vs post-transplant (de Pre-transplant (memory) Abs vs post-transplant (de

novo) antibodies novo) antibodies • represent different processes/risks in the development of AMR represent different processes/risks in the development of AMR • this needs to be explicit in literature/future studiesthis needs to be explicit in literature/future studies

– Timing of Abs appearance with the pathology of the Timing of Abs appearance with the pathology of the biopsy is importantbiopsy is important

• protocols that time blood sampling with lung biopsy are essentialprotocols that time blood sampling with lung biopsy are essential

• Non-HLA antibodies need further study in lung Non-HLA antibodies need further study in lung transplantation patientstransplantation patients

1111thth Banff Conference---Lung Banff Conference---Lung Session Discussion PointsSession Discussion Points

• PathologyPathology– Methodologies for staining C4d are NOT Methodologies for staining C4d are NOT

standardizedstandardized– Interpretation of C4d staining in the lung is Interpretation of C4d staining in the lung is

probably subject to inter-observer variabilityprobably subject to inter-observer variability– Defining (naming) the pathologic pattern of Defining (naming) the pathologic pattern of

injury in biopsies of possible AMR in the lung is injury in biopsies of possible AMR in the lung is not consistentnot consistent• CapillaritisCapillaritis• Capillary injuryCapillary injury• Acute pneumonitisAcute pneumonitis• Acute lung injury with neutrophilsAcute lung injury with neutrophils

1111thth Banff Conference---Lung Banff Conference---Lung Session Discussion PointsSession Discussion Points

• PathologyPathology– Given the overlap of pathologic features of Given the overlap of pathologic features of

AMR with infection, the role of infection in the AMR with infection, the role of infection in the pathology has not been adequately assessed pathology has not been adequately assessed in many published studiesin many published studies

– Incidence of biopsies with possible AMR in Incidence of biopsies with possible AMR in the lung (graft dysfunction, +DSA, +C4d) may the lung (graft dysfunction, +DSA, +C4d) may be quite lowbe quite low

ConclusionsConclusions

• Published data to date are difficult to Published data to date are difficult to interpret given interpret given – Lack of standardization of methodologyLack of standardization of methodology

• Antibody (DSA) measurementAntibody (DSA) measurement• C4d staining/interpretationC4d staining/interpretation

– Inconsistent pathologic descriptionsInconsistent pathologic descriptions– Other etiologies (infection, drug toxicity) not Other etiologies (infection, drug toxicity) not

excludedexcluded

• THE LUNG IS A MESS!THE LUNG IS A MESS!

Background Studies NeededBackground Studies Needed

• Pathology:Pathology:– Consensus for basic definitions of pathologic Consensus for basic definitions of pathologic

patterns of injurypatterns of injury• Education around terminologyEducation around terminology

– Standardization of methodology for staining and Standardization of methodology for staining and for pathologic interpretation of C4dfor pathologic interpretation of C4d

• ImmunologyImmunology– Standardization of antibody measurement Standardization of antibody measurement

methodologymethodology– Routine measurement of both pre- and post- Routine measurement of both pre- and post-

DSAsDSAs

Background Studies NeededBackground Studies Needed

• ClinicalClinical– Protocols that coordinate clinical evaluation Protocols that coordinate clinical evaluation

(graft function), Ab measurement and biopsy (graft function), Ab measurement and biopsy results for accurate comparison of data from results for accurate comparison of data from same time point.same time point.

– Rigorous screening for other causes must be Rigorous screening for other causes must be routinely done routinely done • Infections (cultures and tissue stains)Infections (cultures and tissue stains)• Drug toxicityDrug toxicity

The journey of a thousand miles The journey of a thousand miles begins with a single step……begins with a single step……

Lao-tzu,Lao-tzu,

Chinese philosopher 604 BC - 531 BCChinese philosopher 604 BC - 531 BC

First StepsFirst Steps• Organize lung transplant pathologists (Farver Organize lung transplant pathologists (Farver

and Wallace) with clinicians (Levine and and Wallace) with clinicians (Levine and Glanville) into AMR working groupGlanville) into AMR working group

• Survey for interest Survey for interest – ISHLTISHLT– BanffBanff– Pulmonary Pathology SocietyPulmonary Pathology Society

1212thth Banff Conference Banff Conference

• Working group of AMR in Lung TransplantWorking group of AMR in Lung Transplant• Collection of biopsy slides from possible Collection of biopsy slides from possible

AMR patients from pathologistsAMR patients from pathologists– Digital pathology platforms Digital pathology platforms

• Standard methods forStandard methods for– C4d staining and interpretationC4d staining and interpretation– Standardization of pathology pattern of injury Standardization of pathology pattern of injury

in AMRin AMR• ? grading system…..? grading system…..

Additional Topics Additional Topics

• Infections in Lung Transplant (Stewart)Infections in Lung Transplant (Stewart)– New infections with an update of molecular diagnostic New infections with an update of molecular diagnostic

techniquestechniques– Always in the differential diagnosis (esp. AMR)Always in the differential diagnosis (esp. AMR)

• Progressive, fibrosing parenchymal lung Progressive, fibrosing parenchymal lung diseases post-transplantation (Iversen)diseases post-transplantation (Iversen)– Is there parenchymal form of chronic rejectionIs there parenchymal form of chronic rejection

• Mechanism of endothelial injury in transplanted Mechanism of endothelial injury in transplanted lungs (Belperio)lungs (Belperio)– Chronic vascular rejection: small and large vesselsChronic vascular rejection: small and large vessels

Conference PresentersConference PresentersLung SessionLung Session• Medhat Askar, Cleveland Clinic (USA)Medhat Askar, Cleveland Clinic (USA)• John Belperio, UCLA (USA)John Belperio, UCLA (USA)• Ramsey Hachem, Washington University (USA)Ramsey Hachem, Washington University (USA)• Martin Iversen, Copenhagen University Hospital, Martin Iversen, Copenhagen University Hospital,

(Denmark)(Denmark)• Susan Stewart, Papworth Hospital (UK)Susan Stewart, Papworth Hospital (UK)• W. Dean Wallace, UCLA (USA)W. Dean Wallace, UCLA (USA)Plenary SpeakersPlenary Speakers• Andrew Fisher, Newcastle University (UK)Andrew Fisher, Newcastle University (UK)• Adriana Zeevi, University of Pittsburgh (USA)Adriana Zeevi, University of Pittsburgh (USA)