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Although rheumatoid factor (RF) seropositivity is a risk factor for developing RA-ILD, the relationship between RF seropositivity, mediastinal lymph node (MLN) features, and disease progression is unknown. We aimed to determine if high-titer RF seropositivity predicted MLN features, lung function impairment, and mortality in RA-ILD. In this retrospective cohort study, we identified patients in the University of Chicago ILD registry with RA-ILD. We compared demographic characteristics, serologic data, MLN size, count and location, and pulmonary function over 36\u00a0months among patients who had high-titer RF seropositivity (\u2265\u200960\u00a0IU\/ml) and those who did not. Survival analysis was performed using Cox regression modeling. Amongst 294 patients with CTD-ILD, available chest computed tomography (CT) imaging and serologic data, we identified 70 patients with RA-ILD. Compared to RA-ILD patients with low-titer RF, RA-ILD patients with high-titer RF had lower baseline forced vital capacity (71% vs. 63%; <jats:italic>P<\/jats:italic>\u2009=\u20090.045), elevated anti-cyclic citrullinated peptide titer (122 vs. 201; <jats:italic>P<\/jats:italic>\u2009=\u20090.001), CT honeycombing (50% vs. 80%; <jats:italic>P<\/jats:italic>\u2009=\u20090.008), and higher number of MLN\u2009\u2265\u200910\u00a0mm (36% vs. 76%; <jats:italic>P<\/jats:italic>\u2009=\u20090.005). Lung function decline over 36\u00a0months did not differ between groups. Primary outcomes of death or lung transplant occurred more frequently in the high-titer RF group (HR 2.8; 95% CI 1.1\u20136.8; <jats:italic>P<\/jats:italic>\u2009=\u20090.028). High-titer RF seropositivity was associated with MLN enlargement, CT honeycombing, and decreased transplant-free survival. RF titer may be a useful prognostic marker for stratifying patients by pulmonary disease activity and mortality risk.\n<\/jats:p>","DOI":"10.1038\/s41598-021-02066-9","type":"journal-article","created":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T11:02:33Z","timestamp":1637751753000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["High-titer rheumatoid factor seropositivity predicts mediastinal lymphadenopathy and mortality in rheumatoid arthritis-related interstitial lung disease"],"prefix":"10.1038","volume":"11","author":[{"given":"Albina","family":"Tyker","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iazsmin Bauer","family":"Ventura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathryn T.","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Strykowski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Garcia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Guzy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renea","family":"Jablonski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rekha","family":"Vij","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E.","family":"Strek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan H.","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayodeji","family":"Adegunsoye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,24]]},"reference":[{"issue":"9746","key":"2066_CR1","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1016\/S0140-6736(10)60826-4","volume":"376","author":"DL Scott","year":"2010","unstructured":"Scott, D. 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JHC has received speaking and advisory board fees from Genentech and Boehringer Ingelheim AA has received speaking and advisory board fees from Genentech and Boehringer Ingelheim and is supported by a career development award from the National Heart, Lung, and Blood Institute (NHLBI K23HL146942). All other authors (AT, IBV, CTL, RS, NG, RG, RJ, RV) have no competing interests to disclose.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"22821"}}