Respiratory viral infections can be a novel environmental risk factor for the development of rheumatoid arthritis, find Korean researchers writing in Arthritis Research and Therapy.
The study, which was led by Yune-Jung Park, a rheumatologist with St. Vincent’s Hospital, the Catholic University of Korea, Seoul, and published on August 30 in the journal, found that ambient respiratory viral infections, such as the parainfluenza, coronavirus, and metapneumovirus, were associated with an increased number of incident rheumatoid arthritis cases most often affecting women and older patients.
Dr. Park and colleagues analyzed 24,117 cases (mean age 54.7 years, 77.5% women) of incident rheumatoid arthritis (RA) from weekly incident RA reports from the Korean National Health Insurance claims database, and the Korea Centers for Disease Control and Prevention database.
"The idea of infections acting as a trigger for the development of RA has been suggested for a quite long time without much clarification," Dr. Park and colleagues wrote. "In this study, the number of weekly incident RA cases exhibited an inverted U-shaped seasonal tendency throughout each year. In addition, the detection rate for ambient respiratory viral infections in the population was associated with an increased number of incident RA cases, which suggests a possible role for respiratory infections as a trigger for the development of RA."
After adjusting for time trend, air pollution, and meteorological data, they found that ambient respiratory viral infections in the population were associated with a higher number of incident rheumatoid arthritis cases over time, peaking at six to seven weeks after exposure.
Three of the viruses were associated with an increased number of incident rheumatoid arthritis cases: metapneumovirus (44%, 2.0 to 103.4 with 67.4% affecting women and 118.2% affecting older patients); coronavirus (9.2%, 3.9 to 14.8 with 12.1% affecting women and 14.6% affecting older patients); and, parainfluenza virus (4.8% for 1% respiratory viral infection increase, affecting 3.8% of women and 10.7% affecting older patients).
There are a number possible explanations for virus-induced autoimmune disease: Molecular mimicry which occurs when a virus mimics the host antigen which sparks T-cell cross-reactivity, epitope spreading, bystander activation, the release of encrypted host antigens, and superantigens that activate a wide range of nonspecific T cell clones.
Respiratory viral infections usually involve the oral mucosa and lungs, which may be relevant in rheumatoid arthritis which can affect the oral mucosa and lungs. And, like viral infections, rheumatoid arthritis can be seasonal in nature. In this study, the active rheumatoid arthrits was more common from January through July and then decreasted through December.
"We are interested in determining whether respiratory viral infections have the capacity to drive the development of rheumatoid arthritis, for several reasons. Smoking, periodontitis, and microbiomes, which are all prominent environmental risk factors for RA, interact with mucosal surfaces including the lungs, oral mucosa, and the gastrointestinal tract. It is thought that these local tissue stressors on the mucosa lead to post-translational modification of peptides involved in the pathogenesis of RA," Dr. Park and colleagues wrote.
The authors noted a number of limitations, such as the inability to show a causal association between ambient respiratory viral infections and incident rheumatoid arthritis because it was not known whether the RA patients also had viral infections.
Young Bin Joo, Youn-Hee Lim, Ki-Jo Kim, Kyung-Su Park & Yune-Jung Park. "Respiratory viral infections and the risk of rheumatoid arthritis," Arthritis Research and Therapy. Published: 30 August 2019. https://doi.org/10.1186/s13075-019-1977-9