About this Journal Submit a Manuscript Table of Contents
Journal of Biomedicine and Biotechnology
Volume 2012 (2012), Article ID 594056, 12 pages
http://dx.doi.org/10.1155/2012/594056
Research Article

Effects of IRF5 Lupus Risk Haplotype on Pathways Predicted to Influence B Cell Functions

1Arthritis and Clinical Immunology Program, Oklahoma Medical Research Foundation, 825 NE 13th Street, Oklahoma City, OK 73104, USA
2Department of Microbiology and Molecular Biology, Brigham Young University, 857 WIDB, Provo, UT 84604, USA
3Division of Rheumatology, Cincinnati Children’s Hospital, 3333 Burnet Avenue, Cincinnati, OH 45229, USA
4Departments of Medicine and Pathology, The University of Oklahoma Health Sciences Center, 1100 N. Lindsay, Oklahoma City, OK 73104, USA

Received 5 May 2011; Revised 4 November 2011; Accepted 5 November 2011

Academic Editor: Timothy B. Niewold

Copyright © 2012 Joel M. Guthridge et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Both genetic and environmental interactions affect systemic lupus erythematosus (SLE) development and pathogenesis. One known genetic factor associated with lupus is a haplotype of the interferon regulatory factor 5 (IRF5) gene. Analysis of global gene expression microarray data using gene set enrichment analysis identified multiple interferon- and inflammation-related gene sets significantly overrepresented in cells with the risk haplotype. Pathway analysis using expressed genes from the significant gene sets impacted by the IRF5 risk haplotype confirmed significant correlation with the interferon pathway, Toll-like receptor pathway, and the B-cell receptor pathway. SLE patients with the IRF5 risk haplotype have a heightened interferon signature, even in an unstimulated state ( 𝑃 = 0 . 0 1 1 ), while patients with the IRF5 protective haplotype have a B cell interferon signature similar to that of controls. These results identify multiple genes in functionally significant pathways which are affected by IRF5 genotype. They also establish the IRF5 risk haplotype as a key determinant of not only the interferon response, but also other B-cell pathways involved in SLE.