TY - JOUR
T1 - Alefacept reduces infiltrating T cells, activated dendritic cells, and inflammatory genes in psoriasis vulgaris
AU - Chamian, Francesca
AU - Lowes, Michelle A.
AU - Lin, Shao Lee
AU - Lee, Edmund
AU - Kikuchi, Toyoko
AU - Gilleaudeau, Patricia
AU - Sullivan-Whalen, Mary
AU - Cardinale, Irma
AU - Khatcherian, Artemis
AU - Movitskaya, Inna
AU - Wittkowski, Knut M.
AU - Krueger, James G.
PY - 2005/2/8
Y1 - 2005/2/8
N2 - Psoriasis vulgaris, a skin disease that is considered to be the result of a type 1 autoimmune response, provides an opportunity for studying the changes that occur in a target-diseased tissue during innovative immunotherapies. To gain a more comprehensive picture of the response to an approved biological therapy, we studied alfacept, which is a CD2 binding fusion protein. We examined T cells, dendritic cells (DCs), and expression of a number of inflammatory genes. In 22 patients, 55% demonstrated a clear histological remission of the disease, with a 73% reduction in lesional lymphocytes and a 79% decrease in infiltrating CD8+ cells. Only histological responders showed marked reductions in the tissue expression of inflammatory genes IFN-γ, signal transducer and activator of transcription 1, monokine induced by IFN-γ, inducible NO synthase, IL-8, and IL-23 subunits. Parallel decreases in CD83 + and CD11c+ DCs also were measured by immunohistochemistry. Because we observed that alefacept binds primarily to T cells and not DCs, we suggest that T cells are the primary target for therapy, but that DCs and a spectrum of type 1 inflammatory genes are coordinately suppressed.
AB - Psoriasis vulgaris, a skin disease that is considered to be the result of a type 1 autoimmune response, provides an opportunity for studying the changes that occur in a target-diseased tissue during innovative immunotherapies. To gain a more comprehensive picture of the response to an approved biological therapy, we studied alfacept, which is a CD2 binding fusion protein. We examined T cells, dendritic cells (DCs), and expression of a number of inflammatory genes. In 22 patients, 55% demonstrated a clear histological remission of the disease, with a 73% reduction in lesional lymphocytes and a 79% decrease in infiltrating CD8+ cells. Only histological responders showed marked reductions in the tissue expression of inflammatory genes IFN-γ, signal transducer and activator of transcription 1, monokine induced by IFN-γ, inducible NO synthase, IL-8, and IL-23 subunits. Parallel decreases in CD83 + and CD11c+ DCs also were measured by immunohistochemistry. Because we observed that alefacept binds primarily to T cells and not DCs, we suggest that T cells are the primary target for therapy, but that DCs and a spectrum of type 1 inflammatory genes are coordinately suppressed.
KW - Amevive
KW - Autoimmune disease
KW - CD2
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U2 - 10.1073/pnas.0409569102
DO - 10.1073/pnas.0409569102
M3 - Article
C2 - 15671179
AN - SCOPUS:13844316466
SN - 0027-8424
VL - 102
SP - 2075
EP - 2080
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 6
ER -