The role of chronic lung disease in autoantibody generation; a novel precision medicine description
Research by Scott Matson, M.D., Junior Faculty, Kansas Institute for Precision Medicine COBRE
Autoimmune diseases are caused by the immune system’s generation and deployment of autoantibodies (antibodies that recognize parts of the host body as foreign). The pulmonary system is an important component in this process, as not only a target of autoantibodies, but we believe as an important preclinical site for the generation of autoantibodies. We have identified rates of autoantibodies in patients with chronic lung diseases not traditionally thought to be autoimmune-related such as idiopathic pulmonary fibrosis (IPF) and asthma which are much higher than normal control populations. This finding goes hand in hand with population-based studies which identify higher rates of rheumatoid arthritis (RA, an autoimmune disease) in cohorts of patients with asthma and the development of incident RA in asthma cohorts that is much higher than normal control population rates.
Chronic lung diseases such as IPF and asthma develop through a concert of genetic risk and environmental exposures such as cigarette smoking and inhaled particulate matter. We have identified that local production of these autoantibodies is higher in the lung than serum in these chronic lung diseases. For instance, in bronchoalveolar lavage fluid from patients with IPF we find higher rates of RA autoantibodies than corresponding blood samples, which is similar to findings in sputum from patients with asthma. For this reason, we hypothesize that local inflammatory pressures in the lung lead to the production of autoantibodies. In our preliminary data, we find that lung production of autoantibodies is associated neutrophil extracellular trap formation (NETs).
The long-term goal of this work is to understand the biology of autoantibody development and risk in chronic lung disease states to develop better recognition systems for early autoimmunity and potentially interventional trials to mitigate autoantibody development in lung diseases.
- Matson, S, Lee, J, Eickelberg, O. 2021. Two sides of the same coin? A review of the similarities and differences between idiopathic pulmonary fibrosis and rheumatoid arthritis-associated interstitial lung disease.. The European respiratory journal, 57 (5)
- Matson, S., M, Demoruelle, M., K, Castro, M. 2021. A Focused Review: Airways Disease in Rheumatoid Arthritis.. Annals of the American Thoracic Society
- Matson, S., M, Deane, K., D, Peljto, A., L, Bang, T., J, Sachs, P., B, Walts, A., D, Collora, C, Ye, S, Demoruelle, M., K, Humphries, S., M, Schwartz, D., A, Lee, J., S. 2021. Prospective Identification of Subclinical Interstitial Lung Disease in Rheumatoid Arthritis Cohort is Associated with the MUC5B Promoter Variant.. American journal of respiratory and critical care medicine
- Matson, S., M, Lee, S., J, Peterson, R., A, Achtar-Zadeh, N., A, Boin, F, Wolters, P., J, Lee, J., S. 2021. The prognostic role of matrix metalloproteinase-7 in scleroderma-associated interstitial lung disease.. The European respiratory journal, 58 (6)
- Solomon, J., J, Matson, S, Kelmenson, L., B, Chung, J., H, Hobbs, S., B, Rosas, I., O, Dellaripa, P., F, Doyle, T., J, Poli, S, Esposito, A., J, Visser, A, Marin, A., I, Amigues, I, Fernández Pérez, E., R, Brown, K., K, Mahler, M, Heinz, D, Cool, C, Deane, K., D, Swigris, J., J, Demoruelle, M., K. 2020. IgA Antibodies Directed Against Citrullinated Protein Antigens Are Elevated in Patients With Idiopathic Pulmonary Fibrosis.. Chest, 157 (6), 1513-1521
Scott Matson, M.D.
Assistant Professor of Medicine
Division of Pulmonary, Critical Care and Sleep Medicine
Junior Faculty, Kansas Institute for Precision Medicine COBRE