CD200 Expression in Post-Transplant Lymphoproliferative Disorders Correlates with an Increased Frequency of FoxP3(+) Regulatory T-Cells
James Vaughan, Alexander C Mackinnon, Alexandra M Harrington, Steven H Kroft, Horatiu Olteanu. MCW, Milwaukee, WI
Background: CD200 is a membrane protein with immunosuppressive function. It is expressed in multiple normal cell types, and certain hematopoietic neoplasms, including acute myeloid leukemia (AML), plasma cell myeloma (PCM), and B-cell lymphoproliferative disorders, but is mostly negative in diffuse large cell lymphoma (DLBCL). CD200 has been shown to be a poor prognostic marker in AML and PCM; in AML, its immunomodulatory effect was linked to its ability to induce FoxP3(+) regulatory T cells (Tregs). Post-transplant lymphoproliferative disorders (PTLDs) arise in the setting of immune dysregulation, and tumor-infiltrating T cells, including Tregs, have been shown to correlate with outcome in these disorders. Because there is no literature data and CD200 is a potentially useful diagnostic and prognostic marker, we studied the expression of CD200 in PTLDs by immunohistochemistry (IHC), and correlated it with clinicopathologic parameters, including Treg counts.
Design: 31 consecutive PTLD cases (26 monomorphic: 23 DLBCL and 3 Burkitt lymphoma; 5 polymorphic) had IHC performed with antibodies against CD200, CD3, CD20, CD4, CD8, FoxP3, and TIA-1, according to manufacturer's recommendations. CD200 expression was considered positive when present in >20% lymphoma cells. FoxP3(+) Tregs were determined as an average of cells counted in 10 high-power fields (hpfs, 400x magnification). Clinical data was available from chart review.
Results: 6/31 (19.4%) PTLDs were CD200(+) and showed strong membrane positivity in the neoplastic cells. All CD200(+) monomorphic PTLDs were DLBCLs (5/23, 21.7%). CD200(+) PTLDs occurred in 2/16 (12.5%) kidney, 2/2 heart (100%), 2/8 (25%) stem cell, 0/2 lung, and 0/3 liver recipients. The median FoxP3(+) Treg count/hpf was higher in CD200(+) than in CD200(-) PTLDs: 20.45 vs. 0.30 (p=0.003). There were no other differences, including age, gender, time from transplant to PTLD diagnosis, anatomic site, EBV status, number of infiltrating cytotoxic T cells, and overall survival, between CD200(+) and CD200(-) cases.
Conclusions: 19.4% of PTLDs in our series are CD200(+) by IHC, and CD200 expression correlates with the number of immunosuppressive Tregs. This is novel data and supports the pathophysiologic link between CD200 activity and Tregs. In addition, we find a higher proportion of CD200(+) monomorphic PTLD-DLBCLs (21.7%), as compared to de novo DLBCLs (7% reported in the literature). This may indicate differential expression of CD200 in B-cell lymphomas arising in the setting of immune dysregulation, and raises the possibility of anti-CD200 immunotherapy for these cases.
Monday, March 4, 2013 1:00 PM
Poster Session II # 209, Monday Afternoon