Lindsey Ann Criswell, MD, MPH

University of California, San Francisco, San Francisco, CA

2016 DNA, Genetics, Environmental Triggers

How do pesticides and other chemical exposures influence lupus severity?

The study and what it means to patients

“The more we learn about what causes lupus, the more we can do to treat and possibly prevent this debilitating disease. In our novel research, we will be using cutting-edge technology to analyze the influence of hundreds of chemicals on blood samples from lupus patients in the hopes of discovering how pesticide and chemical exposures may result in severe forms of the disease.”

Summary

It is believed that both genetic and environmental risk factors play a role in causing lupus. Unfortunately, very little is known about the role of environmental exposures in the disease, including the effects of pesticides and other chemicals that may turn genes on and off by a process called DNA methylation.

Previous research has shown that patients with severe cases of lupus have had changes to their DNA through methylation, but how and why this occurs is still poorly understood. In this groundbreaking study, we will determine whether particular chemical exposures influence DNA methylation and disease outcomes in lupus. We will do this by using a new, pioneering technology to analyze blood samples from patients with severe cases of the disease. This innovative technology enables us to analyze the samples for hundreds of chemicals at a time – the first time this type of research has been conducted in lupus. We can then determine what role, if any, exposure to these different chemicals has had on patients with severe manifestations of lupus.

Technical Summary:

Genetic, epigenetic and environmental risk factors have been implicated in the pathogenesis of SLE. Environmental exposures can influence DNA methylation. We have completed genome- wide methylation profiling for a large group of SLE patients and demonstrated significant differences in methylation profiles according to autoantibody status and renal involvement. These differences may represent a link between environmental exposures and SLE manifestations. Very few studies have measured exposures in biological samples of SLE patients. The overall goals of this study are to examine the association of chemical exposures with disease phenotype and DNA methylation patterns in SLE. We will characterize serum levels of environmental organic acids (EOAs) in 400 SLE patients with well characterized disease, including clinical and serologic outcomes; socioeconomic data; as well as genome-wide genetic and DNA methylation profiles. Banked serum will be analyzed by a non-targeted approach with liquid chromatography-quadrupole time of flight mass spectrometry (LC-QTOF/MS). This technology allows for the analysis of hundreds of chemicals in an unbiased manner. We will then determine whether exposure to EOAs is associated with disease phenotype and/or DNA methylation profiles in SLE. This will be the first study assessing environmental exposures, DNA methylation and disease phenotypes in a large cohort of SLE patients.