immunophenotyping intimal arteritis
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Immunophenotyping Intimal Arteritis. Anthony Chang, MD University of Chicago Medical Center. Immunophenotyping intimal arteritis. - PowerPoint PPT PresentationTRANSCRIPT
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