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

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.

Tyker A ，Ventura IB ，Lee CT ，Strykowski R ，Garcia N ，Guzy R ，Jablonski R ，Vij R ，Strek ME ，Chung JH ，Adegunsoye A ... -  《Scientific Reports》

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

Rheumatoid arthritis (RA) is a frequent cause of interstitial lung disease (ILD); however, the impact of rheumatoid factor and anti-citrullinated peptide antibody seropositivity in ILD without connective tissue disease (CTD) is unclear. We examined the association of seropositivity with ILD progression, mortality and response to immunosuppression in non-CTD ILD. A total of 1570 non-CTD patients (with idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, interstitial pneumonia with autoimmune features or unclassifiable ILD) and 181 RA-ILD patients were included from a prospective registry. Longitudinal forced vital capacity (FVC), transplant-free survival and incidence of progressive fibrosing-ILD (PF-ILD) were compared between seronegative non-CTD ILD (reference group), seropositive non-CTD ILD and RA-ILD using linear mixed-effect and Cox proportional hazards models adjusted for age, sex, smoking pack-years and baseline FVC. Interaction between seropositivity and immunosuppression on FVC decline was assessed in patients with ≥6 months of follow-up before and after the treatment. Two hundred and seventeen (13.8%) patients with seropositive non-CTD ILD had similar rates of FVC decline and transplant-free survival compared to seronegative non-CTD ILD, but more frequently met the criteria for PF-ILD (hazard ratio [HR] = 1.35, p = 0.004). RA-ILD had slower FVC decline (p = 0.03), less PF-ILD (HR = 0.75, p = 0.03) and lower likelihood of lung transplant or death (HR = 0.66, p = 0.01) compared to seronegative non-CTD ILD. No interaction was found between seropositivity and treatment on FVC decline in non-CTD ILD. Seropositivity in non-CTD ILD was not associated with improved outcomes or treatment response, highlighting the importance of other disease features in determining prognosis and predicting response to immunosuppression.

Zheng B ，Donohoe K ，Hambly N ，Johannson KA ，Assayag D ，Fisher JH ，Manganas H ，Marcoux V ，Khalil N ，Kolb M ，Ryerson CJ ，CARE-PF Investigators ... -  《-》

Clinical characteristics associated with occurrence and poor prognosis of interstitial lung disease in rheumatoid arthritis.

Yang JA ，Lee JS ，Park JK ，Lee EB ，Song YW ，Lee EY ... -  《-》

Risk factors for the progression of rheumatoid arthritis-related interstitial lung disease: Clinical features, biomarkers, and treatment options.

The clinical heterogeneity of the progression of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is high, and there is a lack of consensus on the clinical relevance and medical protocols. The purpose of this study is to explore the impact of clinical characteristics, new biomarkers and treatment options on the prognosis of RA-ILD patients and to explore whether these factors can predict the progression and death of these patients. We retrospectively collected case data on RA-ILD patients who visited or were admitted to Changhai Hospital between October 2010 and September 2021. We followed up and finally included 75 patients. The main outcome indicator of disease progression was pulmonary functional impairment, which was assessed by changes of high-resolution computed tomography (HRCT) score or pulmonary function test before and after treatment. The demographics, clinical characteristics, laboratory tests, and treatment plans of RA-ILD patients in the progressive and stable groups were compared and analyzed. Clinically relevant variables were identified, and the incidence of pulmonary dysfunction and adverse events was recorded. Cox regression analysis was used to determine factors related to the progression of ILD. The mean age of RA-ILD onset was 64.0 years (SD 10.3), and 53 (70.7%) patients were female. Thirty-two (42.7%) patients had lung dysfunction, who were classified as the progressive group, and 13 (40.6%) of them died. In univariate analyses, male, smoking, high HRCT scores at baseline, RF-IgA>200 RU/ml, diffusing capacity of the lungs for carbon monoxide (DLCO), and usual interstitial pneumonia (UIP) pattern were significant risk factors for disease progression; while use of Leflunomide (LEF) was associated with better prognosis. The multivariate analysis revealed that RF-IgA>200 RU/ml (hazard ratio [HR] 3.17 [95% confidence interval (CI) 1.29, 7.81], P = 0.012), UIP pattern (HR 3.94 [95% CI 1.68, 9.26], P = 0.002), and male (HR 2.52 [95% CI 1.16, 5.46], P = 0.019) were significantly correlated with unfavorable outcomes in patients with RA-ILD. LEF (HR 0.25 [95% CI 0.10, 0.61], P = 0.002) was related to a better prognosis. However, it might be related to investigating medications changes after baseline. Our data suggests that male, UIP pattern, and increased RF-IgA may be potential predicting factors for poor prognosis of RA-ILD patients. We report a significant association between high titer of RF-IgA at baseline and RA-ILD progression for the first time, which might be a potentially important biomarker for the prognosis of RA-ILD.

Chen N ，Diao CY ，Gao J ，Zhao DB ... -  《-》

Distinctive Clinical Characteristics and Outcome of ILD-Onset Rheumatoid Arthritis and ACPA-Positive ILD: a Longitudinal Cohort of 282 Cases.

Chen RX ，Zhao LD ，Xiao XY ，Song L ，Du HY ，Xu ZJ ，Feng RE ，Yang HX ，Fei YY ，Zhang W ，Zhang FC ，Chen H ，Zhang X ... -  《-》