Evaluating the Perception Among Rheumatologists of Maintenance of Board Certification in the US

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/148252/1/acr23823.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148252/2/acr23823-sup-0001-AppendixS1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/148252/3/acr23823_am.pd

An update on belimumab for the treatment of lupus

B-lymphocyte stimulator (BLyS), a homeostatic factor for B-cell differentiation and survival, has a major role in B-cell expansion and autoreactivity that characterize systemic lupus erythematosus (SLE). Belimumab, a BLyS-specific inhibitor, has shown promising evidence of efficacy in several preclinical and clinical studies in SLE. Two recent large randomized controlled trials yielded a significant positive effect of the drug compared to placebo in patients with active disease. In this review, we discuss basic aspects of B-cell and BLyS biology in SLE and summarize the evidence supporting a role of belimumab in SLE, from animal studies to phase III clinical trials

Glycoprotein nonmetastatic melanoma protein B: A key mediator and an emerging therapeutic target in autoimmune diseases

The glycoprotein nonmetastatic melanoma protein B (GPNMB, also known as osteoactivin) is highly expressed in many cell types and regulates the homeostasis in various tissues. In different physiological contexts, it functions as a melanosome- associated protein, membrane- bound surface receptor, soluble ligand, or adhesion molecule. Therefore, GPNMB is involved in cell differentiation, migration, inflammation, metabolism, and neuroprotection. Because of its various involvement in different physiological conditions, GPNMB has been implicated in many diseases, including cancer, neurological disorders, and more recently immune- mediated diseases. This review summarizes the regulation and function of GPNMB in normal physiology, and discusses the involvement of GPNMB in disease conditions with a particular focus on its potential role and therapeutic implications in autoimmunity.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155959/1/fsb220630.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155959/2/fsb220630_am.pd

Identification of Cysteineâ Rich Angiogenic Inducer 61 as a Potential Antifibrotic and Proangiogenic Mediator in Scleroderma

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150582/1/art40890.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150582/2/art40890_am.pd

EZH2 Modulates the DNA Methylome and Controls T Cell Adhesion Through Junctional Adhesion Molecule A in Lupus Patients

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141024/1/art40338_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/141024/2/art40338.pd

Ethnicity-specific epigenetic variation in naïve CD4+ T cells and the susceptibility to autoimmunity

Abstract Background Genetic and epigenetic variability contributes to the susceptibility and pathogenesis of autoimmune diseases. T cells play an important role in several autoimmune conditions, including lupus, which is more common and more severe in people of African descent. To investigate inherent epigenetic differences in T cells between ethnicities, we characterized genome-wide DNA methylation patterns in naïve CD4+ T cells in healthy African-Americans and European-Americans, and then confirmed our findings in lupus patients. Results Impressive ethnicity-specific clustering of DNA methylation profiling in naïve CD4+ T cells was revealed. Hypomethylated loci in healthy African-Americans were significantly enriched in pro-apoptotic and pro-inflammatory genes. We also found hypomethylated genes in African-Americans to be disproportionately related to autoimmune diseases including lupus. We then confirmed that these genes, such as IL32, CD226, CDKN1A, and PTPRN2 were similarly hypomethylated in lupus patients of African-American compared to European-American descent. Using patch DNA methylation and luciferase reporter constructs, we showed that methylation of the IL32 promoter region reduces gene expression in vitro. Importantly, bisulfite DNA sequencing demonstrated that cis-acting genetic variants within and directly disrupting CpG sites account for some ethnicity-specific variability in DNA methylation. Conclusion Ethnicity-specific inherited epigenetic susceptibility loci in CD4+ T cells provide clues to explain differences in the susceptibility to autoimmunity and possibly other T cell-related diseases between populations.http://deepblue.lib.umich.edu/bitstream/2027.42/116042/1/13072_2015_Article_37.pd

Identification of novel genetic susceptibility loci for Behçet's disease using a genome-wide association study

Introduction Behcet's disease is a chronic systemic inflammatory disease that remains incompletely understood. Herein, we perform the first genome-wide association study in Behcet's disease

Inhibition of EZH2 Ameliorates Lupusâ Like Disease in MRL/lpr Mice

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151823/1/art40931_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151823/2/art40931.pd