She concluded that smoking does not necessarily cause disease but may help set the stage for disease to occur. “It’s not producing the disease, it’s changing the backdrop upon which exposures and experiences act to produce the pathogenic response to these antibodies,” Dr. Cooper said.
She discussed the initial smoking and disease research that began in the 1940s and 1950s. Research specifically connecting smoking and RA began in the late 1980s and early 1990s. This research actually grew out of an investigation into oral contraceptives and RA, which was not originally intended to explore smoking and RA. “The body of research developed because the data were there,” she said. “By 2006, there were more than 50 studies looking at RA and smoking.”
Various data show a modest risk between smoking and RA, involving an interaction between smoking, the HLA shared epitope, and anticyclic citrullinated protein–antibody positivity, Dr. Cooper said.
“What these data lead to is that smoking leads to generation of modified peptides in the lungs. That interaction is reflecting a particular affinity of the DRB epitope and its ability to bind those peptides. That activation involves other genetic variants and environmental exposures, and all leads to priming for system immunity,” she said.
Dr. Cooper also detailed research connecting silica dust to autoimmune disease. This research goes back almost 100 years and has focused mostly on occupational exposure for miners, foundry workers, and various construction trade workers. Autoimmune diseases associated with this exposure include RA, lupus, and scleroderma.
“With silica, as with smoking, you have the potential for immune effects in the lungs that have more profound implications in terms of systemic effects,” Dr. Cooper said. This includes destruction of macrophages via the release of intracellular peptides.
Dr. Cooper said that the actual exposure to silica and smoking may occur years before disease onset. She also noted that exposure in the lungs does not just stay in the lungs—it also has effects on the immune system. Finally, she highlighted the role of prevention.
“From a public health perspective, prevention is cheaper, more effective, and more productive, and that might be where we want to put our efforts,” she said.
Genes and Environmental Interactions
Research that focuses on lupus and the gene–environment interaction was the focus of a presentation by Judith James, MD, PhD, Lou Kerr Endowed Chair in biomedical research at the Oklahoma Medical Research Foundation in Oklahoma City. Among various research that Dr. James discussed was a study in the area of associated lupus genetic haplotypes interacting with the Epstein-Barr virus to induce lupus autoimmunity. There is also research into interferon regulatory factor 5 (IRF5) and a possible strong genetic association with lupus. “The hypothesis is that IRF5 risk and nonrisk haplotypes will drive distinguishable host gene expression patterns in B cells. We saw differences and see some genes upregulated because they have IRF5 haplotypes,” Dr. James said.
