Systemic lupus erythematosus and increased risk to develop B cell malignancies: role of the p200-family proteins.

Abstract

Systemic lupus erythematosus (SLE), an autoimmune disease, develops at a female-to-male ratio of 10:1. Increased serum levels of type I interferons (IFN-alpha/beta) and induction of "IFN-signature" genes are associated with an active SLE disease in patients. Moreover, SLE patients exhibit three- to four-fold increase in the risk of developing malignancies involving B cells, including non-Hodgkin lymphoma (NHL) and Hodgkin's lymphoma (HL). Interestingly, homozygous mice expressing a deletion mutant (the proline-rich domain deleted) of the p53 develop various types of spontaneous tumors, particularly of B cell origin upon aging. The deletion is associated with defects in transcriptional activation of genes by p53 and inhibition of DNA damage-induced apoptosis. Notably, increased levels of the p202 protein, which is encoded by the p53-repressible interferon-inducible Ifi202 gene, in B cells of female mice are associated with defects in B cell apoptosis, inhibition of the p53-mediated transcription of pro-apoptotic genes, and increased lupus susceptibility. In this review we discuss how increased levels of the p202 protein (and its human functional homologue IFI16 protein) in B cells increase lupus susceptibility and are likely to increase the risk of developing certain B cell malignancies. A complete understanding of the molecular mechanisms that regulate B cell homeostasis is necessary to identify SLE patients with an increased risk to develop B cell malignancies.

• Authors: Sudhakar Veeranki, Divaker Choubey
• Journal: Immunology letters (Immunol Lett) Vol. 133 Issue 1 Pg. 1-5 (Sep 06 2010) ISSN: 1879-0542 [Electronic] Netherlands
• PMID: 20599558 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S., Review)
• Copyright: Published by Elsevier B.V.

Chemical References

• Ifi202b protein, mouse
• Intracellular Signaling Peptides and Proteins
• Nuclear Proteins
• Phosphoproteins
• Tumor Suppressor Protein p53
• IFI16 protein, human

Topics

• Animals
• Apoptosis (genetics, immunology)
• B-Lymphocytes (immunology, metabolism, pathology)
• Female
• Genetic Predisposition to Disease
• Humans
• Intracellular Signaling Peptides and Proteins (genetics, metabolism)
• Lupus Erythematosus, Systemic (epidemiology, genetics, immunology)
• Lymphoma, B-Cell (epidemiology, genetics, immunology)
• Mutation (genetics)
• Nuclear Proteins (genetics, metabolism)
• Phosphoproteins (genetics, metabolism)
• Risk
• Sex Factors
• Transcriptional Activation (genetics, immunology)
• Tumor Suppressor Protein p53 (immunology, metabolism)