Lung summary from 12th Banff Conference on Transplant Pathology from the meeting in Comandatuba-Bahia, Brazil on August 23rd, 2013 http://cybernephrology.ualberta.ca/banff/2013

1. ISHLT Pathology Council &
Pulmonary AMR
12th
Banff Conference on Allograft
Pathology
Thursday, August 22, 2013
GERRY BERRY

2. Pulmonary AMR in 2013
• Historical Highlights
• 2012 ISHLT Survey of Pathology
Practices
• Recommendations from ISHLT 2012
in Prague
• Future Directions

3. 2012 Survey of Current Practices in Diagnosis
and Reporting of Pulmonary AMR
• Survey modeled on successful approach by
AECVP for Cardiac AMR *
• Survey consisted of 33 questions created in
REDCap and supported by Stanford Center
for Clinical Informatics in Stanford SOM
• Survey sent to 38 institutions in North
America, Europe and Australia
* Burke M, Andersen C, Ashworth M, et al. J Heart Lung Transplant 2010; 29:S37-38.

4. Demographics

5. Experience in Reading Biopsies

6. Monthly Transbronchial Biopsy Load

7. Antibodies used in IHC

8. Conclusions #1
• Group (90%) composed of experienced
pathologists (> 5 yrs experience)
• > 80% of groups evaluating > 10 TBBx/mo
• Primary indications for immunostaining are
clinical and histopathological findings
• Few centers (25%) perform immunostaining
according to protocols

9. Conclusions #2
Indications of performing Immunostains
• Acute Lung Injury Pattern (66%)
• Neutrophilic Margination (70%)
• Acute Capillaritis (85%)
• Unexplained Graft Dysfunction (2/3)
• High Grade ACR (22%)

10. J Heart &
Lung Transplant 2013; 32:14-21

11. Histopathologic Indications for
Immunopathologic Staining
• Neutrophilic Capillaritis
• Neutrophilic Septal Margination
• High Grade ACR
• Persistent/Recurrent ACR
• Acute Lung Injury Pattern/DAD
• High Grade LB (B2R)
• Persistent low grade LB (Grade B1R)
• Obliterative Bronchiolitis (Grade C1)
• Arteritis in the Absence of Infection or ACR
• Graft Dysfunction without Morphologic Explanation
• Any Histologic Findings in setting of de novo +ve DSA

12. Interpretative Issues in AMR
• Distribution of C4d Staining:
– Multifocal/Diffuse staining >50% of
microvasculature: POSITIVE
– Focal or <50% staining: NEGATIVE
– Any C4d staining should be discussed with
clinicians as findings might warrant DSA
studies and more frequent clinical monitoring

13. Diagnostic Terminology
• Like ACR, AMR is diagnosis of exclusion
• Requires clinical dysfunction, circulating DSA and C4d
immunoreactivity
“No Evidence of AMR”
“Findings Suggestive of AMR”
• Insufficient experience for making recommendations for
follow-up intervals

14. Summary & Future Directions
• Diagnosis of pulmonary AMR requires multidisciplinary approach
• Histopathological findings are nonspecific patterns of injury; patterns
should trigger immunostaining
• Qualified terminology should be used with final clinical diagnosis
incorporating all modalities
• For centers that do not routinely obtain DSA, studies should be done at
or near time of biopsy
• Centers are encouraged to develop protocols that will promote
investigations addressing issues of time to onset of AMR, incidence,
prevalence, spectrum of temporal, morphological and
immunopathological changes, clinical outcomes and risk for chronic
allograft dysfunction
• Digital pathology slide technology will be used to promote educational
and collaborative efforts

15. Adriana Zeevi PhD (D) ABHI
Professor of Pathology, Surgery and
Immunology
University of Pittsburgh Medical Center
Serology of Lung AMR

16. Summary
 Recurrent ACR, refractory to increased
immunosuppression is associated with
development of de-novo DSA.
 The most frequent DSAs in LTx were HLA-DQ
specific including Abs towards DQB, DQA and
combination of DQB/DQA pairs.
 Persistent DQ specific DSAs with C1q reactivity
are demonstrated prior to diagnosis of AMR.
 Response to AMR treatment is associated with
Diminished and/ or Loss of C1q reactive DSAs.

17. Summary/Conclusions
 Pre-formed and de-novo DSA are associated with
various forms of antibody injury to allograft
 Non HLA antibodies need to be evaluated for the
impact on LTX
 Early detection of DSA post LTx and systematic
monitoring with sensitive solid-phase platforms is
recommended
 Antibody depletion protocols need to be
evaluated: when and how

18. Anti-human leukocyte antigen antibodies
and preemptive antibody-directed therapy
after lung transplantation
Survival was
significantly worse in
recipients who had
persistent DSA than
in those who cleared
the DSA.
Ramsey R. Hachem, MD, et al J Heart Lung Transplant 2010;29:973–80

19. Clinical Overview of Pulmonary
AMR
Marie M. Budev DO MPH FCCP
Medical Director Lung and Heart Lung
Transplant Program
Cleveland Clinic
Cleveland, OH

20. Triple Test - Diagnosis of
Pulmonary AMR
Serologic Evidence
Donor Specific Antibody
+
Graft Dysfunction
Histological Evidence
Histopathology + C4d
staining
+

21. AAMR and SurvivalAAMR and Survival
• Survival afterSurvival after
AMR is poorAMR is poor
• Cleared DSACleared DSA
significantlysignificantly
better survivalbetter survival
Witt CA. In Press : J Heart Lung Transplant. 2013

22. Clinical Points AAMR StudyClinical Points AAMR Study
• Survival is poor after AAMRSurvival is poor after AAMR
• Survival is better if DSA clearedSurvival is better if DSA cleared
• AAMR may be a reversible cause ofAAMR may be a reversible cause of
allograft failureallograft failure
• High index of suspicion with protocolHigh index of suspicion with protocol
for surveillance in place including HLAfor surveillance in place including HLA
testingtesting
- C4d still controversialC4d still controversial
• Role of C1qRole of C1q

23. HLA ANTIBODIES AFTER LUNGHLA ANTIBODIES AFTER LUNG
TRANSPLANTATION: EARLYTRANSPLANTATION: EARLY
RESULTS OF THE HALT STUDYRESULTS OF THE HALT STUDY
The HALT InvestigatorsThe HALT Investigators

24. HALT: Multicenter StudyHALT: Multicenter Study
• Washington UniversityWashington University
– R. Hachem, R. Yusen, K. Schechtman, J. Gaut, T. MohanakumarR. Hachem, R. Yusen, K. Schechtman, J. Gaut, T. Mohanakumar
• Cleveland ClinicCleveland Clinic
– M. Budev, C. Farver, M. AskarM. Budev, C. Farver, M. Askar
• University of PennsylvaniaUniversity of Pennsylvania
– V. Ahya, J. Lee, L. Litzky, M. KamounV. Ahya, J. Lee, L. Litzky, M. Kamoun
• UTHSC San AntonioUTHSC San Antonio
– D. Levine, S. Werner-Abboud, M. PollackD. Levine, S. Werner-Abboud, M. Pollack
• Stanford UniversityStanford University
– G. Dhillon, D. Weill, G. Berry, D. TyanG. Dhillon, D. Weill, G. Berry, D. Tyan
• University of California San FranciscoUniversity of California San Francisco
– L. Leard, J. Golden, K. Jones, L. Baxter-LoweL. Leard, J. Golden, K. Jones, L. Baxter-Lowe

25. MethodsMethods
• Pilot prospective multicenterPilot prospective multicenter
observational studyobservational study
• Standardize DSA monitoringStandardize DSA monitoring
• Determine incidence of DSADetermine incidence of DSA
development (DSA profiles)development (DSA profiles)
• Enrollment 12/2011 – 6/2012Enrollment 12/2011 – 6/2012
• 4 months follow-up after transplant4 months follow-up after transplant
• LABScreen® Single Antigen assayLABScreen® Single Antigen assay
- Days: 10, 30, 60, 90, 120Days: 10, 30, 60, 90, 120
- Allograft dysfunctionAllograft dysfunction

26. Patient flow diagram

27. Acute cellular rejectionAcute cellular rejection
• At least 1 episode of ACR grade ≥ A1At least 1 episode of ACR grade ≥ A1
- DSA-: 44/68 (65%)DSA-: 44/68 (65%)
- DSA+: 25/36 (69%)DSA+: 25/36 (69%)
• At least 1 episode of ACR grade ≥ A2At least 1 episode of ACR grade ≥ A2
- DSA-: 26/68 (38%)DSA-: 26/68 (38%)
- DSA+: 16/36 (44%)DSA+: 16/36 (44%)
• CARS: sum of all A scoresCARS: sum of all A scores
- DSA-: mean = 1.5 ± 1.5, median = 1.0DSA-: mean = 1.5 ± 1.5, median = 1.0
- DSA+: mean = 1.7 ± 1.6, median = 1.5DSA+: mean = 1.7 ± 1.6, median = 1.5
P = 0.63
P = 0.54
P = 0.70

28. Antibody-mediated rejectionAntibody-mediated rejection
• 4 cases of AMR (adjudicated)4 cases of AMR (adjudicated)
• Occurred on POD 22, 46, 75, and 92Occurred on POD 22, 46, 75, and 92
• Clinical allograft dysfunctionClinical allograft dysfunction
• DSA to class I & II (n = 4)DSA to class I & II (n = 4)
– Pre-tx DSA (n = 1): higher MFI and new DSAPre-tx DSA (n = 1): higher MFI and new DSA
– De novoDe novo DSA (n = 3)DSA (n = 3)
• Alveolar septal neutrophilia (n = 2), no biopsy (n =Alveolar septal neutrophilia (n = 2), no biopsy (n =
2)2)
– C4d & C3d negative (n = 2)C4d & C3d negative (n = 2)
• Clinical response to IVIG, high-dose steroidsClinical response to IVIG, high-dose steroids

29. ConclusionsConclusions
• DSA is common early afterDSA is common early after
transplantationtransplantation
• DSA to HLA class II more commonDSA to HLA class II more common
• HALT follow-up too short to examineHALT follow-up too short to examine
impact on clinical outcomesimpact on clinical outcomes
• Some patients did clear DSA duringSome patients did clear DSA during
follow-upfollow-up
• Long-term follow-up is necessary &Long-term follow-up is necessary &
planned with HALT II Trialplanned with HALT II Trial

30. Banff Study of PathologicBanff Study of Pathologic
Changes in Lung AllograftChanges in Lung Allograft
Biopsies with Donor SpecificBiopsies with Donor Specific
AntibodiesAntibodies
Comandatuba, BrazilComandatuba, Brazil
August 2013August 2013

31. Banff 2011Banff 2011
Paris, FranceParis, France
Lung Group DiscussionLung Group Discussion
Data for pathology of lungData for pathology of lung
AMR was limited/lackingAMR was limited/lacking
The data on C4d wasThe data on C4d was
inconsistent, probably unreliableinconsistent, probably unreliable
AMR in lung allograft was not aAMR in lung allograft was not a
pathologic diagnosis at that timepathologic diagnosis at that time
Large study needed to gatherLarge study needed to gather
pathologic data on lungpathologic data on lung
transplant biopsiestransplant biopsies
Should be multi-institutionalShould be multi-institutional
Results to be presented at BanffResults to be presented at Banff
2013 in Brazil2013 in Brazil
Mengel M, et al. Banff 2011 Meeting report: new concepts in antibody-mediated rejection.
Am J Transplant. 2012 Mar;12(3):563-70.

32. Banff StudyBanff Study
• Team Leaders: Carol Farver, W. Dean WallaceTeam Leaders: Carol Farver, W. Dean Wallace
• Lung transplant transbronchial biopsies were compiledLung transplant transbronchial biopsies were compiled
from UCLA and Cleveland Clinicfrom UCLA and Cleveland Clinic
• 253 lung transplant biopsies (62 biopsies have C4d stains)253 lung transplant biopsies (62 biopsies have C4d stains)
– Mean age: 55.8, Range: 18-74Mean age: 55.8, Range: 18-74
– Gender: 111 females (43.9%), 142 males (56.1%)Gender: 111 females (43.9%), 142 males (56.1%)
• Inclusion criteria:Inclusion criteria:
– All biopsies have full serologic antibody studies performed withinAll biopsies have full serologic antibody studies performed within
((++) 30 days of biopsy) 30 days of biopsy
• 98 de novo DSAs (38.7%)98 de novo DSAs (38.7%)
• 46 non-DSAs (18.2%)46 non-DSAs (18.2%)
• 109 never antibodies (43.1%)109 never antibodies (43.1%)
– Full clinical/infectious disease work up dataFull clinical/infectious disease work up data
– At least 1 year old at beginning of studyAt least 1 year old at beginning of study

33. PathologistsPathologists
• Biopsies are scanned for whole slide imageBiopsies are scanned for whole slide image
analysis for ease of sharinganalysis for ease of sharing
• Eleven pathologists participated in blinded studyEleven pathologists participated in blinded study
– Carol Farver, Cleveland ClinicCarol Farver, Cleveland Clinic
– W. Dean Wallace, UCLAW. Dean Wallace, UCLA
– Claus B. Andersen, Rigshospitalet, CopenhagenClaus B. Andersen, Rigshospitalet, Copenhagen
– Valeria Arrossi, Cleveland ClinicValeria Arrossi, Cleveland Clinic
– Roberto Barrios, The Methodist Hospital, HoustonRoberto Barrios, The Methodist Hospital, Houston
– Gerry Berry, StanfordGerry Berry, Stanford
– Matthew DeNicola, UCLAMatthew DeNicola, UCLA
– Desley Neil, Queen Elizabeth Hospital, Birmingham,Desley Neil, Queen Elizabeth Hospital, Birmingham,
UKUK
– Elizabeth Pavlisko, Duke UniversityElizabeth Pavlisko, Duke University
– Myriam Remmelink, Brussels, BelgiumMyriam Remmelink, Brussels, Belgium
– Birgit Weynand, Brussels, BelgiumBirgit Weynand, Brussels, Belgium

34. Histologic VariablesHistologic Variables
• Biopsy AdequacyBiopsy Adequacy
• Acute Cellular RejectionAcute Cellular Rejection
• Airway InflammationAirway Inflammation
• Obliterative BronchiolitisObliterative Bronchiolitis
• Acute Lung InjuryAcute Lung Injury
• EndotheliitisEndotheliitis
• Alveolar HemosiderosisAlveolar Hemosiderosis
• Capillary InflammationCapillary Inflammation
• Suspicion for Aspiration?Suspicion for Aspiration?
• Other Infection?Other Infection?
• C4d depositionC4d deposition

35. Primary questions to be asked…Primary questions to be asked…
• Is there correlation with capillary inflammation and/orIs there correlation with capillary inflammation and/or
acute lung injury and DSAs?acute lung injury and DSAs?
• What is significance of C4d deposition?What is significance of C4d deposition?
Secondary questions…Secondary questions…
• Does ACR correlate with DSAs?Does ACR correlate with DSAs?
• Is there correlation between endothelialitis and DSAs?Is there correlation between endothelialitis and DSAs?
• Percent of biopsies suboptimal or inadequatePercent of biopsies suboptimal or inadequate
• Percent of biopsies without airwaysPercent of biopsies without airways
• What is inter-observer reliability for various histologicWhat is inter-observer reliability for various histologic
categoriescategories

36. Limitations of StudyLimitations of Study
• Whole slide imaging not as good as glass slidesWhole slide imaging not as good as glass slides
for capillary analysisfor capillary analysis
• Only 1 level examinedOnly 1 level examined
• Restriction of choices by dropdown menuRestriction of choices by dropdown menu
• Variability in interpretation of ALI and capillaryVariability in interpretation of ALI and capillary
inflammation (do we need better definitions?)inflammation (do we need better definitions?)
• C4d performed at one institution onlyC4d performed at one institution only
• Have not included antibody titer levelsHave not included antibody titer levels

38. Acute Cellular RejectionAcute Cellular Rejection

39. Frequency for pooled dataFrequency for pooled data

40. Comparisons between D, A , and NComparisons between D, A , and N
Average ACR Score 0.336 0.365 0.304

41. Acute Lung InjuryAcute Lung Injury
• Regarded as a spectrum from reactiveRegarded as a spectrum from reactive
pneumocytes with interstitial/alveolar edemapneumocytes with interstitial/alveolar edema
(above baseline) to diffuse alveolar damage(above baseline) to diffuse alveolar damage
(DAD).(DAD).
• Any degree of ALI less than DAD wasAny degree of ALI less than DAD was
categorized as “ALI”.categorized as “ALI”.
• Hyaline membranes indicated DADHyaline membranes indicated DAD
• If acute inflammation consistent with acuteIf acute inflammation consistent with acute
pneumonia, “Acute pneumonia, favor infection”pneumonia, “Acute pneumonia, favor infection”

43. DSA

44. Frequency of ALIFrequency of ALI

45. Comparison Data
Average ALI Score 0.187 0.322 0.128

46. EndothelialitisEndothelialitis

47. EndothelialitisEndothelialitis

48. Capillary InflammationCapillary Inflammation
• Capillary inflammation determined by degree ofCapillary inflammation determined by degree of
neutrophils in alveolar capillaries. neutrophils in alveolar capillaries.
• Does not include areas with hemorrhage or crushDoes not include areas with hemorrhage or crush
artifact. artifact.
• Best area with preserved lung architecture. Best area with preserved lung architecture.
– 0=normal, generally few or no neutrophils. 0=normal, generally few or no neutrophils.
– 1=more than normal but no back-to-back (touching)1=more than normal but no back-to-back (touching)
neutrophilsneutrophils
– 2=more than baseline AND back-to-back neutrophils2=more than baseline AND back-to-back neutrophils
– 3=frank capillaritis with karyorrhectic debris and hemorrhage3=frank capillaritis with karyorrhectic debris and hemorrhage

49. Normal alveolar capillariesNormal alveolar capillaries

50. Above baseline and 2 or moreAbove baseline and 2 or more
neutrophils back-to-backneutrophils back-to-back

51. Capillary InflammationCapillary Inflammation

52. DSA

53. DSA

54. DSA

55. DSA

56. Non-DSA

57. DSA vs NegativeDSA vs Negative

58. Comparisons between D, A and NComparisons between D, A and N
Average CI Score 0.264 0.362 0.224

59. Capillary inflammation vs ALICapillary inflammation vs ALI

60. C4d DepositionC4d Deposition
• C4d measured as:C4d measured as:
– NegativeNegative
– Positive, <50%Positive, <50%
– Positive, >50%Positive, >50%
– Not performedNot performed
• Measured in alveolar capillaries onlyMeasured in alveolar capillaries only
• 62 biopsies had C4d stains62 biopsies had C4d stains
• Full data from Cleveland Clinic 177 cases withFull data from Cleveland Clinic 177 cases with
C4dC4d

61. DSA

63. C4d is correlated with ALI with DAD, increasing ACR
and Capillary Inflammation but not ALI alone.

64. Cleveland Clinic DataCleveland Clinic Data

65. Inter-Observer VariabilityInter-Observer Variability

66. Where were we in 2011?Where were we in 2011?

67. Putative Stages of Humoral Response toPutative Stages of Humoral Response to
an Organ Graft – 2003 NIHan Organ Graft – 2003 NIH
recommendationsrecommendations
I: Latent humoral responseI: Latent humoral response
Circulating antibody alone (without biopsy findings or graftCirculating 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 histologicCirculating antibody, (without histologic
changes or graft dysfunction)changes or graft dysfunction)
III: Sub-clinical humoral rejectionIII: Sub-clinical humoral rejection
Circulating antibody, tissue pathologyCirculating antibody, tissue pathology
(without graft dysfunction)(without graft dysfunction)
IV: Humoral rejectionIV: Humoral rejection
Circulating antibody, tissue pathology, graftCirculating 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 depositionC4d deposition
C4d deposition,C4d deposition,
C4d deposition,C4d deposition,

68. Putative Stages of Humoral Response toPutative Stages of Humoral Response to
an Organ Graft – 2003 NIHan 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 graftCirculating antibody alone (without biopsy findings or graft
dysfunction)dysfunction)
III: Sub-clinical humoral rejectionIII: Sub-clinical humoral rejection
Circulating antibody, (without graftCirculating antibody, (without graft
dysfunction)dysfunction)
IV: Humoral rejectionIV: Humoral rejection
Circulating antibody, graft dysfunctionCirculating antibody, graft dysfunction
tissue pathologytissue pathology
tissue pathology,tissue pathology,

69. I: Latent humoral response/Silent humoral reaction/Sub-I: Latent humoral response/Silent humoral reaction/Sub-
clinical humoral rejectionclinical humoral rejection
Circulating antibody alone (without biopsy findings or graftCirculating antibody alone (without biopsy findings or graft
dysfunction)dysfunction)
II: Humoral rejectionII: Humoral rejection
Circulating antibody, graft dysfunctionCirculating antibody, graft dysfunction

70. Where are we in 2013?Where are we in 2013?

71. Recent StudiesRecent Studies
• Yousem and ZeeviYousem and Zeevi (Am J Surg Pathol 2012;36:987–992).(Am J Surg Pathol 2012;36:987–992).
– Found 23 pts with HLA Abs and lung dysfunctionFound 23 pts with HLA Abs and lung dysfunction
– 17 had concurrent high grade ACR17 had concurrent high grade ACR
– 18% had capillaritis18% had capillaritis
– C4d seen in 76% (vs 24% of controls)C4d seen in 76% (vs 24% of controls)
• DeNicola, Weigt, Wallace et al.DeNicola, Weigt, Wallace et al. (J Heart Lung(J Heart Lung
Transplant 2013;32:326-332).Transplant 2013;32:326-332).
– 41 pts, 16 with anti-HLA abs41 pts, 16 with anti-HLA abs
– Capillary neutrophilic inflammation and DAD were tested asCapillary neutrophilic inflammation and DAD were tested as
histologic markers for AMRhistologic markers for AMR

72. ISHLT and BanffISHLT and Banff
• G Berry, et al. Pathology of pulmonaryG Berry, et al. Pathology of pulmonary
antibody-mediated rejection: 2012 update fromantibody-mediated rejection: 2012 update from
the Pathology Council of the ISHLT. JHLTthe Pathology Council of the ISHLT. JHLT
2013; 32: 14-12.2013; 32: 14-12.
• Banff StudyBanff Study

73. Putative Stages of Humoral Response toPutative Stages of Humoral Response to
an Organ Graft – 2003 NIHan Organ Graft – 2003 NIH
recommendationsrecommendations
I: Latent humoral responseI: Latent humoral response
Circulating antibody alone (without biopsy findings or graftCirculating 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 histologicCirculating antibody, (without histologic
changes or graft dysfunction)changes or graft dysfunction)
III: Sub-clinical humoral rejectionIII: Sub-clinical humoral rejection
Circulating antibody, tissue pathologyCirculating antibody, tissue pathology
(without graft dysfunction)(without graft dysfunction)
IV: Humoral rejectionIV: Humoral rejection
Circulating antibody, tissue pathology, graftCirculating 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 depositionC4d deposition
C4d deposition,C4d deposition,
C4d deposition,C4d deposition,

74. Putative Stages of Humoral Response toPutative Stages of Humoral Response to
an Organ Graft – 2003 NIHan 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 graftCirculating antibody alone (without biopsy findings or graft
dysfunction)dysfunction)
III: Sub-clinical humoral rejectionIII: Sub-clinical humoral rejection
Circulating antibody, (without graftCirculating antibody, (without graft
dysfunction)dysfunction)
IV: Humoral rejectionIV: Humoral rejection
Circulating antibody, graft dysfunctionCirculating antibody, graft dysfunction
tissue pathologytissue pathology
tissue pathology,tissue pathology,

75. Is it that simple?Is it that simple?
• NoNo
• The histologic differences are significant but areThe histologic differences are significant but are
neither sensitive nor specific for the presence ofneither sensitive nor specific for the presence of
DSA.DSA.
• Who would care if they were?Who would care if they were?
• The question is:The question is:
– Are the findings sensitive or specific for graftAre the findings sensitive or specific for graft
deterioration in the setting of DSA????deterioration in the setting of DSA????

76. InvestigatorsInvestigators
• PathologistsPathologists
– Carol FarverCarol Farver
– W. Dean WallaceW. Dean Wallace
– Claus B. AndersenClaus B. Andersen
– Valeria ArrossiValeria Arrossi
– Roberto BarriosRoberto Barrios
– Gerry BerryGerry Berry
– Matthew DeNicolaMatthew DeNicola
– Desley NeilDesley Neil
– Elizabeth PavliskoElizabeth Pavlisko
– Myriam RemmelinkMyriam Remmelink
– Birgit WeynandBirgit Weynand
• UCLAUCLA
– Sam WeigtSam Weigt
– Ning LiNing Li
– Elaine ReedElaine Reed
– Jennifer ZhangJennifer Zhang
• Cleveland ClinicCleveland Clinic
– Marie BudevMarie Budev
– Medhat AskarMedhat Askar
– Rene SlawRene Slaw
– Sol CristomoSol Cristomo