CD Markers
CD40
Copyright: 2002-2021, PathologyOutlines.com, Inc.
PubMed Search: CD40 [title]
CD40
Author: Nat Pernick, M.D.
Topic Completed: 1 January 2011
Minor changes: 2 October 2020
Copyright: 2002-2021, PathologyOutlines.com, Inc.
PubMed Search: CD40 [title]
Table of Contents
Definition / general | Terminology | Pathophysiology | Clinical features | Uses by pathologists | Prognostic factors | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative staining | Additional referencesCite this page: Pernick N. CD40. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cdmarkerscd40.html. Accessed January 16th, 2021.
Definition / general
- Costimulatory protein found on antigen presenting cells, required for their activation
Terminology
- Also called TNF receptor superfamily member 5; ligand is CD40L (CD154)
Pathophysiology
- 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
Clinical features
- Cardiovascular disease:
- May mediate inflammatory component of atherogenesis
- Variation of CD40 gene is associated with coronary artery calcification in diabetes (Am Heart J 2006;151:706)
- 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)
- CD40 mediated platelet activation may play a role in thrombosis, inflammation and atherosclerosis (Circ Res 2003;92:1041)
- Effects may be mediated by soluble form of CD40L (Ann Med 2011;43:331)
- 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;286:9948)
Uses by pathologists
- No significant clinical use by pathologists
Prognostic factors
- 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)
Microscopic (histologic) images
Images hosted on other servers:
Soft tissue sarcomas
Positive staining - normal
- 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
- Kaposi sarcoma (Am J Pathol 1996;148:1387)
- Melanoma (Am J Pathol 1996;149:1953)
- Reed-Sternberg cells in Hodgkin 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
- Plasma cells, Gaucher cells, prostatic adenocarcinoma (Oncol Rep 2004;12:679)
Additional references
