Session Type: Poster Session A
Session Time: 8:30AM-10:30AM
Background/Purpose: Idiopathic pulmonary fibrosis (IPF) is a form of interstitial lung disease (ILD) that shares many clinical features with rheumatoid arthritis (RA) associated ILD. Our published data found that serum RA-related antibodies, particularly IgA antibodies to CCP, were significantly more prevalent in IPF patients (23%) compared to population controls (6%). However, the mechanisms that lead to anti-CCP generation in IPF are unknown. Of interest, neutrophil extracellular trap (NET) formation externalizes citrullinated proteins and has been implicated in the generation of anti-CCP in RA, including in the lung. The goal of this study was to explore relationships between anti-CCP, markers of NET formation in the lung and outcomes in IPF.
Methods: We included 176 IPF patients from National Jewish Health who had stored bronchoalveolar lavage fluid (BALF). BALF was analyzed for anti-CCP-IgA (in house ELISA), total protein (ELISA) and markers of NETs (neutrophil elastase (NE), ELISA, and double stranded (ds)DNA, fluorometric assay). All CCP, NE and dsDNA values were adjusted for total protein level. Date of death was determined by the CDC’s National Death Index and mortality was analyzed by Spearman’s correlation using days from BALF collection to death within 5 years of BALF collection and cox proportional hazards model. The majority of patients (n=169) also had pulmonary function testing (PFTs), including % predicted forced vital capacity (% FVC) and % predicted diffusion capacity of carbon monoxide (% DLCO), performed within 3 months of BALF collection.
Results: Clinical characteristics of the cohort are listed in Table 1. Overall, we found a significant association between higher levels of BAL anti-CCP and lower 5-year mortality (Figure 1A). In contrast, we found a significant association between higher levels of dsDNA and NE and higher 5-year mortality (Figure 1B-C). Of interest, when IPF patients were stratified by BALF anti-CCP level, the ‘Low BALF anti-CCP’ group had a significant correlation between markers of NETosis and clinical variables including: 5-year mortality, %FVC and %DLCO while the ‘High BALF anti-CCP’ group had no association between NETosis markers and these outcomes (Table 2). There was also a significant positive correlation between BALF levels of anti-CCP and markers of NETs (for NE, r=0.20, p=0.010; for dsDNA, r=0.27, p< 0.001).
Conclusion: This is the first study to report anti-CCP-IgA levels in the lung of IPF patients and identify an association with improved mortality. We also found a strong association between anti-CCP and markers of NETs in the lung, suggesting that NETs may lead to anti-CCP generation in the lung in IPF, similar to reports in RA. Based on published studies in IPF that associate BALF neutrophilia with increased mortality, it was not surprising that NET markers in BALF were associated with mortality in our study. However, it was of interest that this association was markedly blunted in IPF patients with the highest BALF anti-CCP levels, suggesting that anti-CCP-IgA may be protective against the detrimental effects of neutrophils in the lung in IPF. Future studies are needed to understand the mechanisms by which such a protective effect in the lung could occur.
To cite this abstract in AMA style:Matson S, Cephers C, Wilson T, Minarchick V, Brown K, Solomon J, Demoruelle K. IgA Anti-Cyclic Citrullinated Peptide Antibodies in Bronchoalveolar Lavage Fluid from Patients with Idiopathic Pulmonary Fibrosis Are Associated with Reduced Mortality [abstract]. Arthritis Rheumatol. 2021; 73 (suppl 10). https://acrabstracts.org/abstract/iga-anti-cyclic-citrullinated-peptide-antibodies-in-bronchoalveolar-lavage-fluid-from-patients-with-idiopathic-pulmonary-fibrosis-are-associated-with-reduced-mortality/. Accessed January 22, 2022.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/iga-anti-cyclic-citrullinated-peptide-antibodies-in-bronchoalveolar-lavage-fluid-from-patients-with-idiopathic-pulmonary-fibrosis-are-associated-with-reduced-mortality/