High-titer rheumatoid factor seropositivity predicts mediastinal lymphadenopathy and mortality in rheumatoid arthritis-related interstitial lung disease

Abstract

Rheumatoid arthritis-related interstitial lung disease (RA-ILD) is a common connective tissue disease-related ILD (CTD-ILD) associated with high morbidity and mortality. 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 months among patients who had high-titer RF seropositivity (≥ 60 IU/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%; P = 0.045), elevated anti-cyclic citrullinated peptide titer (122 vs. 201; P = 0.001), CT honeycombing (50% vs. 80%; P = 0.008), and higher number of MLN ≥ 10 mm (36% vs. 76%; P = 0.005). Lung function decline over 36 months 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 1.1–6.8; P = 0.028). 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.

Clinical relevance of rheumatoid factor and anti‐citrullinated peptides in fibrotic interstitial lung disease

“…However, the imperfect predictive ability of these clinical features raises the question of whether additional factors may provide further prognostic information. RF and ACPA presence have previously been associated with increased mortality in RA and RA‐ILD, 27,28 but their prognostic impact in other ILD subtypes is unknown. We found that seropositivity was associated with increased PF‐ILD in IPF and unclassifiable ILD, whereas seropositivity was associated with slower FVC decline in HP.…”

Unmet needs and perspectives in rheumatoid arthritis-associated interstitial lung disease: A critical review

“…RF positivity is an established risk factor for ILD development in patients with RA ( 65 – 67 ). It has been demonstrated that the prevalence and incidence of RA-ILD correlates with serum titers of RF ( 68 ) and high-titer RF is associated with an increased risk of progression and elevated mortality in patients with RA-ILD ( 69 ), along with a more aggressive form of RA with a higher risk of erosions ( 70 ). Moreover, signs of advanced fibrosis at HRCT (including honeycombing) have been associated with RF seropositivity in patients with RA-ILD ( 69 ).…”

Tomographic pleuropulmonary manifestations in rheumatoid arthritis: a pictorial essay

“…Linfonodomegalias axilares e mediastinais podem ocorrer em 20-70% dos pacientes com AR, especialmente naqueles com AR-DPI. (4,28) A fisiopatologia subjacente a essas linfonodomegalias permanece incerta. No entanto, sugere-se que a migração de células imunes da circulação periférica através dos linfonodos mediastinais para os pulmões contribua para a fibrose pulmonar.…”

“…Axillary and mediastinal lymph node enlargement may occur in 20-70% of patients with RA, especially in those with RA-ILD. 4 , 28 The biology underpinning this enlargement remains unclear. However, migration of immune cells from the peripheral circulation through mediastinal lymph nodes to the lungs has been suggested to contribute to pulmonary fibrosis.…”