How Nutrition May Affect DNA to Trigger Lupus Flares


(AUDIO) Bruce Richardson MD describes strong evidence that environmental sources such as sunlight and diet alter DNA processing to affect immune cell function and influence the course of lupus.

After decades of inquiry, Bruce Richardson[[{"type":"media","view_mode":"media_crop","fid":"25781","attributes":{"alt":"Bruce Richardson MD","class":"media-image media-image-right","id":"media_crop_9944124842353","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"2417","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"width: 114px; height: 132px; float: right;","title":" ","typeof":"foaf:Image"}}]] and his coworkers have made great strides in puzzling out how the environment and genetics interact to trigger lupus. Mouse research has painted a clear picture of how oxidative stress (or exposure to some medications) can interfere with the genetic signals that control the action of T helper cells.

Numerous lines of evidence suggest that these observations are relevant to humans with lupus. Today, as recipient of the second Lupus Insight Prize, Dr. Richardson is poised begin studies that would to confirm whether environmental sources such as sunlight and poor diet truly disrupt T-cell signaling in this way in lupus patients.

In this brief recorded interview, Dr. Richardson describes the history of this research, and reveals its direct implications for the way you counsel your patients with lupus now.

Dr. Richardson is Professor of Medicine at the University of Michigan and Chief of Rheumatology at the Veteran's Affairs Ann Arbor Healthcare System

The Lupus Insight Prize is a result of collaboration between the Alliance for Lupus Research, the Lupus Foundation of America, and the Lupus Research Institute.

The questions:

What is epigenetics and what is the evidence that it's involved in lupus?

Is this phenomenon uniquely important to lupus
among autoimmune and rheumatic disorders, or is it also relevant to other rheumatic disorders?

What are you going to do with the award money to move the field forward?

What are the practical implications of this research for rheumatology practice?

Key quotes:

"If you inhibit DNA methylation in dividing helper T cells ... [they] lose that requirement for the antigen, but would respond to the host antigen-presenting cells without any antigen, meaning that they're now auto-reactive."

"We've found that procainamide and hydralazine, the drugs most commonly implicated in causing lupus, are both DNA methylation inhibitors."

"Oxidative stress plays an important role in causing these epigenetic changes in the T cells ... and works much like the drugs that cause lupus."

"Part of the funding will ... allow us to look at oxidative damage and nutritional status in these patients and relate it to disease activity, the hypothesis ... being that the greater the oxidative damage and the worse the diet, the more severe the lupus is going to be."


See also:  Prizewinning Insights Into the Future of Lupus Research

(AUDIO) Dr. Mark Shlomchik, first recipient of the Lupus Insight Prize, describes the work that led to the development of the new lupus biologic called belimumab, and forthcoming studies that will illuminate the role of infection in the disease.


Cornacchia E, Golbus J, Maybaum J, et al: Hydralazine and procainamide inhibit T cell DNA methylation and induce autoreactivity. J Immunol  (1988) 140:2197-2200.

Richardson BC, Strahler JR, Pivirotto TS, et al.Phenotypic and functional similarities between 5-azacytidine treated T cells and a T cell subset in patients with active systemic lupus erythematosus. Arthritis Rheum (1992) 35:647-662.

Quddus J, Johnson KJ, Gavalchin J, et al. Treating activated CD4+ T cells with either of two distinct DNA methyltransferase inhibitors, 5-azacytidine or procainamide, is sufficient to induce a lupus-like disease in syngeneic mice. J Clin Invest  (1993) 92:38-53.

Richardson B.  Epigenetics of AutoimmunityNature Clinical Practice Rheumatology (2007) 3:521-527.

Li Y, Liu Y, Strickland F, Richardson B.  Age-dependent decreases in DNA methyltransferase levels and low transmethylation micronutrient levels synergize to promote overexpression of genes implicated in autoimmunity and acute coronary syndromes. Experimental Gerontol (2010) 45:312-322.

Webb R, Kelly JA, Somers EC, et alEarly disease onset is predicted by a higher genetic risk for lupus and is associated with a more severe phenotype in lupus patients.Ann Rheum Dis (2011) 70: 151-156.

Sawalha A, Wang L, McCune WJ, et alSex-specific differences in the relationship between genetic susceptibility, T cell DNA demethylation and lupus flare severity.  J Autoimmun (2012) 38: 216-222.

Gorelik GJ, Yardlagadda S, Richardson BC.  Protein kinase Cδ oxidation contributes to ERK inactivation in lupus T cells.  Arthritis Rheum (2012) 64:2964-2974

Strickland F, Hewagama A, Wu A, et al. Diet Influences Expression of Autoimmune Associated Genes and Disease Severity By Epigenetic Mechanisms in a Transgenic Lupus Model.Arthritis Rheum (2013) 65, 1872-1881.

Li Y, Gorelik G, Strickland F and Richardson B. Oxidative Stress, T Cell DNA Methylation and LupusArthritis Rheum (2014) 66:1574-82.

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