Rheumatoid Arthritis: Pollutants and Genetics

Researchers from the University of Michigan School of Medicine report that environmental factors such as cigarette smoke and other pollutants may heighten the risk for developing rheumatoid arthritis (RA) in genetically susceptible individuals and may be responsible for more severe damage when RA occurs. The work investigated the effect of pollutants on a gene variant, human leukocyte antigen (HLA) that is long known to be associated with increased risk for development of RA. It has also been observed that smokers who carry the HLA gene variant have an even greater risk for RA, and for higher disease severity, as manifested by greater pain and swelling, and more extensive bone destruction. Of the relationship between the HLA gene and environmental pollutants, Joseph Holoshitz, MD, professor of internal medicine and associate chief for research in the Division of Rheumatology at Michigan Medicine, summarized, “We found a particular enzyme that acts as a channel, or pathway, in the cell for a conversation between the two culprits, so they work together to do greater damage. Individually they are bad, but together, they’re worse.”

Working with mouse models, the Michigan Medicine team found that the interaction of dioxin and other pollutants, and the HLA gene variant activates a pathway associated with RA and that can facilitate bone degeneration. The latter results from overabundant and hyperactive osteocytes that are triggered by the dioxin-HLA variant interaction. Dr. Holoshitz notes that bone destruction resulting from RA is a lesser known and more dangerous outcome from the disease, that current RA treatments fail to directly address. His team is developing some drug candidates that block the HLA gene activated pathway, and that may be effective in inhibiting bone damage in mice. He observed: “Once we have better drugs that directly and specifically address bone destruction in this disease, we’ll have better treatment.” The findings were published in the Proceedings of the National Academy of Sciences.

Read more about the research findings.

The journal article may be read here.