- Routine C4d staining on all pancreas allograft biopsies is the current practice to diagnose antibody-mediated rejection (AMR). - C4d staining along with detectable donor-specific antibodies remain the best method to diagnose AMR in pancreas transplants. - Typical morphologic findings may not be apparent in early or late cases of AMR. - Further studies are needed to examine all aspects of C4d staining and its relationship to donor-specific antibodies and morphological findings in the diagnosis of AMR. - There is also a need to further develop and define criteria for chronic (active) AMR.

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PANCREAS ALLOGRAFTS SESSION: SUMMARY

2. • Jon Odorico
Pancreatic AMR – Clinicopathological
correlations and experience at Wisconsin-
Madison.

3. Study Design
• Single center, retrospective study of “for-cause”
pancreas
allograft biopsies
• 94 Bx from 49 patients
• 162 Pancreas Transplants 2006-09
All biopsies had C4d staining – IHC on paraffin sections
• Majority (79/94) of bx had DSA data – Luminex SAB
assay
Niederhaus et al. AJT, in press

4. Summary Acute AMR
of the Pancreas Transplant
• Acute AMR Occurs in ~10% of patients in the first year
• Risk Factors: Solitary pancreas transplant, Non-
primary SPK transplant, Donor/recipient race
mismatch, Female recipient
• Patients having AMR did not have worse graft survival
than patients having AMR/ACR or ACR, but do have
worse outcomes than patients having no rejection
• DSA+C4d- rejection is uncommon but does occur,
C4d+DSA- rejection occurs; DSA alone is not
diagnostic Niederhaus et al. AJT in press

5. • Surya Seshan

7. Summary and Conclusions
• Routine C4d staining on all pancreas allograft
biopsies is the current practice.
• C4d staining along with detectable DSA remain
the best method to diagnose AbMR in pancreas
transplants.
• Typical morphologic findings may not be
apparent in early or late AbMR cases.
• Further studies to examine all aspects of C4d
staining and its relationship to DSA and
morphological findings in the diagnosis of AbMR
is needed.
• Further develop and define criteria for chronic
(active) AbMR.

8. • Hanneke de Kort

9. Banff 2013 9
1. Biopsy data:
Leiden + Maryland
de Kort et al, 2010 AJT

10. Banff 2013 10
2. Tq data: Leiden
AMR negative
Suspicious for
AMR
Acute AMR

11. Banff 2013 11
3. Data: London
• All 17 Tq; DSA and C4d negative
• 58 bx;
– 8 Bx had no arteries sampled
– Includes PAK and PTA

12. Banff 2013 12
Conclusion
Consistency with kidney so far
For pancreas allografts intimal arteritis can
be indicative of ACMR as well as AMR,
regardless of the severity

13. Immunophenotypical studies on
pancreas tx inflammation
Erika Rangel (15 bx, CD68)
John Papadimitriou (46 bx, CD3,CD20,CD68)

14. Discussion (Erika Rangel)
 Macrophage infiltration in pancreas graft:
 Occurs in both acute AMR and TCMR
 Is associated with the severity of the TCMR
 Has negative impact on pancreas graft survival
 Does not occur in significant numbers in the later
fibrosing stages

15. Conclusions (John Papadimitriou)
CD3 increase proportionally with grades
of ACMR, AMR and stage.
CD20 increase proportionally with
ACMR and AMR and stage.
CD68 increase proportionally with ACMR
and AMR, but not stage.

16. CD3 CD3
CD20 CD20
ACMR I-II
Stage I-II
*

17. Diagnosis of rejection in grafted duodenal
cuff
Determine if a biopsy of the grafted
duodenal cuff can be a surrogate for a
pancreas biopsy

18. Erik Larsson and team – Ongoing
prospective studies
Uppsala University, Sweden
•Approximately 200 samples in 50 patients
•Have used these biopsies for clinical
monitoring and guidance of therapeutic
decisions
•Excellent graft outcomes

19. Danniele Holanda – Pilot retrospective
studies on archival material of 21 pancreas
samples incidentally containing duodenal
tissue, to evaluate the degree of
concordance of pathological findings in each
pair.
There was >70% full concordance in the
diagnosis and grade of rejection.
The rest of the sampled were discordant but
the disagreement was of no more than 1
grade (i.e. indeterminate vs grade 1)

20. Myriam Leon Fradejas (Malaga, Spain)
Graft failure due to deposition of islet amyloid

21. Under recognition of Islet
processes
• The Banff pancreas group started working
on a set of recommendations for a
diagnostic algorithm of late hyperglycemia
in order to aid in the identification of islet
pathology: recurrent autoimmune DM and
islet amyloidosis.
• Topic of extensive discussions on 2011
Banff meeting.

22. Issues with diagnostic criteria
and grading schema
• “capillaritis”
• Vascular lesions
• etc
• Hanneke de Kort and Candice Roufosse
have made a preliminary analysis of the
most important issues that need attention
and this will be the basis to proceed with
group discussions.

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Good bye Comandatuba…