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CD Markers

CD40


Reviewers: Nat Pernick, M.D., (see Reviewers page)
Revised: 28 January 2011, last major update January 2011
Copyright: (c) 2002-2011, PathologyOutlines.com, Inc.

General
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● Costimulatory protein found on antigen presenting cells, required for their activation

Terminology
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● Also called TNF receptor superfamily member 5; ligand is CD40L (CD154)

Physiology
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● Plays a central role in regulating cell-mediated immunity and antibody mediated immunity
● Also mediates T cell dependent immunoglobulin class switching, memory cell development and germinal center formation

Diagrams
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Model of CD40

Clinical features
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● Cardiovascular disease: (a) may mediate inflammatory component of atherogenesis; (b) variation of CD40 gene is associated with coronary artery calcification in diabetes (Am Heart J 2006;151:706); (c) CD40/CD40L signaling contributes to inflammatory and prothrombogenic responses and brain infarction induced by middle cerebral artery occlusion and reperfusion (Circulation 2005;111:1690) and to acute cerebral ischemia (Stroke 2003;34:1412); (d) CD40 mediated platelet activation may play a role in thrombosis, inflammation and atherosclerosis (Circ Res 2003;92:1041); (e) effects may be mediated by soluble form of CD40L (Ann Med 2011 Jan 18 [Epub ahead of print)
● Has role in pathogenesis of various autoimmune disorders (Semin Immunol 2009;21:293)
● Mutations may cause hyper IgM disease type 3 (OMIM 606843) with opportunistic infections due to inability of B cells to undergo type switching and to defective T cell mediated immunity (Blood 2003;102:4099)
● CD40-CD40L binding may cause microglial activation, and contribute to Alzheimer's disease (CNS Neurol Disord Drug Targets 2010;9:149)
● Epithelial CD40 may cause inflammatory disorders, generation of self-tolerance and chronic rejection of allografts (Semin Immunol 2009;21:289)
● EBV LMP1 is a constitutively active functional mimic of CD40, utilizing TNFR-associated factor adaptor proteins to induce signaling (J Biol Chem 2011 Jan 24 [Epub ahead of print])

Uses
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● No significant clinical use by pathologists

Prognostic value in tumors
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● Expression in >50% of cells may have poor prognostic value in adult soft tissue sarcomas (Clin Cancer Res 2004;10:2824)
● CD40+ diffuse large B cell lymphomas are associated with favorable survival (Clin Cancer Res 2004;10:2824)

Micro images
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Staining in various adult soft tissue sarcomas

Positive staining (normal)
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● B cells, dendritic cells, macrophages, mast cells, monocytes, platelets
● Also astrocytes, endothelial cells, fibroblasts, keratinocytes, Langerhans cells (in oral mucosa), microglia, nevus cells, pancreatic islet cells (Diabetologia 2005;48:268), prostatic acini, other epithelial cells

Positive staining (disease)
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● Kaposiís sarcoma (Am J Pathol 1996;148:1387)
● Melanoma (Am J Pathol 1996;149:1953)
● Reed-Sternberg cells in Hodgkin's lymphoma (70%, Am J Pathol 1994;144:21)
● Most B cell lymphomas (70% of diffuse large B cell lymphoma), B-ALL (some)
● Carcinomas: renal cell (Cell Immunol 2005;235:145), squamous cell carcinoma of oral mucosa (J Oral Pathol Med 2006;35:268), thyroid (Thyroid 2005;15:105)

Negative staining
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● Plasma cells, Gaucher cells, prostatic adenocarcinoma (Oncol Rep 2004;12:679)

Additional references
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OMIM 109535

End of CD Markers > CD40


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