From our prospective study investigating genetic and environmental risks for the development of RA-related autoimmunity, our group enrolled more than 1,000 first-degree relatives and discovered high prevalence of genetic risk factors and RA-related antibodies. However, there was an association between these antibodies and tender joints and C-reactive protein (CRP) levels, suggesting that these autoantibodies are valid intermediate markers of RA-related autoimmunity.
To further evaluate the hypothesis that the lung is involved in the earliest phases of development of RA-related autoimmunity, we assessed the lungs in subjects with RA-related autoantibody positivity without inflammatory arthritis and compared these findings to antibody negative controls, as well as patients with early but established RA. We utilized spirometry and high-resolution computed tomographic lung imaging. We found that 76 percent of antibody-positive subjects had airways abnormalities, including bronchial wall thickening, bronchiectasis, centrilobular opacities and air trapping, compared with 33 percent of controls. These findings were similar to those found in the early RA subjects. Our data support the hypothesis that the lung may be the initial site of autoimmunity-related injury and could possibly be the trigger for the disease.
A total of 251 Hispanic subjects from Los Angeles County were extensively studied by our group with a battery of disease and psychosocial testing. These patients represent low socioeconomic status, uninsured and immigrant populations collectively described as “vulnerable patients.” Our data indicate a high prevalence of significant depression in Hispanics with RA. We found that 32 percent of all subjects and 24 percent of those even with low disease activity had a PHQ-9 score equal to or greater than 10, which is double that found in the general population and on the high end of literature reports for RA. Depression appeared to be durable and a pivotal determinant of self-reported disability over time in spite of what appears to be adequate control of RA disease activity with aggressive biologic drug strategies. The findings are capable of generating intervention strategies that could have a major impact on disease and patient outcome.