Immunophenotyping intimal arteritis
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Immunophenotyping Intimal Arteritis. Anthony Chang, MD University of Chicago Medical Center. Immunophenotyping intimal arteritis.

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Immunophenotyping Intimal Arteritis

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Immunophenotyping intimal arteritis

Immunophenotyping Intimal Arteritis

Anthony Chang, MD

University of Chicago Medical Center


Immunophenotyping intimal arteritis1

Immunophenotyping intimal arteritis

  • Is there a difference in the immunophenotype of lymphocytes in the setting of intimal arteritis associated with T cell-mediated rejection (TCMR) versus antibody-mediated rejection (AMR)?


Literature review

Literature Review

  • Intimal arteritis immunophenotype studies

    • Tuazon TV et al. Am J Pathol 1987

      • CD8, CD4

    • Alpers C, et al. Mod Pathol 1990

      • CD45, UCHL-1 (CD45RO or memory T cells)

      • L-26 (CD20+ B cells)

      • HAM-56 (macrophages, endothelium)

      • Leu-M1 (CD15 granulocytes), Factor VIII and Ulex uropaeus (endothelium), HHF-35 (smooth muscle actin), S100 (DCs, some macrophages)

      • 22 cases


Literature review1

Literature Review

  • Intimal arteritis immunophenotype studies

    • Matheson P, et al. Transplantation 2005

      • UCHL-1 (CD45RO T cells)

      • CD68 (macrophages)

      • 8 of 24 bxs with type II or III rejection

      • CD68 > UCHL-1

    • Kozakowski N, et al. NDT 2009

      • CD68/CD3 ratio in 116 arteries from 34 patients

        • Did not correlate with C4d

        • Did not correlate with worse graft survival


Literature review2

Literature Review

  • Intimal arteritis immunophenotype studies

    • Sementilli A, et al. Tx Proceedings 2010

      • CD68, CD4/CD8, CD20, S100

      • IL-4, IL-10, interferon-gamma

      • 10 of 40 bxs with type II rejection

      • CD8 > CD68


Immunophenotyping intimal arteritis2

Immunophenotyping intimal arteritis

  • Is immunophenotype of lymphocytes in the setting of intimal arteritis associated with T cell-mediated rejection (TCMR) different from the lymphocytes associated with antibody-mediated rejection (AMR)?


Our study

Our study

  • Intimal arteritis/endarteritis lesions

    • U of Chicago Med Ctr (n=20)

    • Cedar Sinai Med Ctr (n=12)

      • 15 – AMR only, 11 – TCMR+AMR, 6 – TCMR only

  • Immunohistochemistry

    • CD3, CD8, CD4, Foxp3

    • CD20

    • CD68 and CD163

    • CD56


Cd3 t cells

CD3+ T cells


Cd3 t cells1

CD3+ T cells


Cd8 t cells

CD8+ T cells


Tregs cd4 foxp3

Tregs (CD4+/foxp3+)

1 of 13 cases


Tregs cd4 foxp31

Tregs (CD4+/foxp3+)


Immunophenotyping intimal arteritis

CD68


Cd163

CD163

  • Scavenger receptor

  • Limited to macrophage/monocyte lineage


Cd1631

CD163


Cd1632

CD163


Cd68 cd163

CD68 / CD163

CD68

CD163


Cd20 b cells

CD20+ B cells


Cd20 b cells1

CD20+ B cells


Cd20 b cells2

CD20+ B cells

  • 5 of 29 cases with any CD20+ B cells

    • 2 with isolated v lesions and C4d+

      • 1 DSA+ class II, 1 DSA+ class I+II

    • 1 with isolated v lesion

      • C4d+ 5% of ptc, DSA/PRA-not tested

    • 1 with TCMR and AMR

      • C4d+ 5-10% of ptc, high PRA class I/II, DSA-

    • 1 isolated v lesion

      • C4d-, PRA/DSA-

    • 15 isolated v lesions with AMR only


Immunophenotyping intimal arteritis

CD56


Cd56 ncam

CD56 (NCAM)


Cd56 ncam1

CD56 (NCAM)


Immunophenotyping intimal arteritis

CD56


Immunophenotyping intimal arteritis

CD56


Cd56 ncam2

CD56 (NCAM)

  • 9 CD56+ cases

    • No more than 4 CD56+ NK cell present

    • 2 cases with CD56 granular staining only; no CD56+ lymphocytes

  • Of 9 isolated v lesions

    • 7 with either CD56+ cell (n=5) or granular staining (n=2)

  • 7 of 10 CD56 staining with AMR alone

  • 0 of 2 CD56 staining in TCMR alone

  • 2 of 10 CD56 staining in TCMR+AMR


Summary

Summary

  • CD56 may be a useful marker to distinguish intimal arteritis associated with AMR from TCMR

    • Additional studies

  • CD20 – infrequent

  • CD3, CD8, CD68, CD163 – no significant difference


Acknowledgement

Acknowledgement

  • Collaborators

    • Mark Haas, Cedars Sinai Medical Center


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