Immunophenotyping Intimal Arteritis

Anthony Chang, MD

University of Chicago Medical Center

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• 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 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 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 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

• 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

CD8+ T cells

Tregs (CD4+/foxp3+)

1 of 13 cases

Tregs (CD4+/foxp3+)

CD68

CD163

• Scavenger receptor

• Limited to macrophage/monocyte lineage

CD163

CD163

CD68 / CD163

CD68 CD163

CD20+ B cells

CD20+ B cells

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

CD56

CD56 (NCAM)

CD56 (NCAM)

CD56

CD56

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

• 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

• Collaborators– Mark Haas, Cedars Sinai Medical Center