Serologic phenotypes distinguish systemic lupus erythematosus patients developing interstitial lung disease and/or myositis

Abstract

Objectives To determine if serologic phenotypes could be identified in systemic lupus erythematosus patients developing interstitial lung disease (ILD) and/or myositis. Methods Adult SLE patients (without myositis/ILD at baseline) had annual assessments and serum sampling between 2000 and 2017. New-onset ILD was identified using the SDI pulmonary fibrosis item. New-onset myositis was identified using the SLICC Damage Index muscle atrophy/weakness item, the SLEDAI-2K item for myositis, and annual creatinine kinase testing. Chart review confirmed ILD/myositis cases and randomly sampled SLE patients from baseline formed our sub-cohort (N = 72). Cases and sub-cohort were compared regarding myositis-related biomarkers at baseline and at a randomly selected follow-up between baseline and end of observation (date of ILD/myositis diagnosis or Dec. 31, 2017). Descriptive analyses and hazards ratios (HRs) were generated for ILD/myositis incidence, focusing on baseline serology and adjusting for sex, race/ethnicity, age at SLE diagnosis, and SLE duration. Results Fourteen SLE patients developed ILD (N = 9), myositis (N = 3), and/or both (N = 2). Thirteen of those (92.9%) developing ILD/myositis had at least one biomarker at baseline, versus 47 (65.3%) SLE patients who never developed myositis/ILD. The most common biomarkers in myositis/ILD were KL-6, anti-Ro52, and anti-Ku. Baseline biomarkers tended to remain positive in follow-up. In multivariate Cox regressions, SLE patients had higher risk of developing myositis/ILD with elevated baseline KL-6 (adjusted hazard ratio 3.66; 95% confidence interval 1.01, 13.3). When updating biomarkers over time, we also saw correlations between anti-Smith and ILD/myositis. Conclusions Baseline myositis-related biomarkers were highly associated with ILD/myositis incidence. This is the first identification of biomarker phenotypes with ILD/myositis risk in SLE.

Role of Advanced Glycation End Products as New Biomarkers in Systemic Lupus Erythematosus

“…Two controversial points were raised during the analysis. First, we observed only a positive trend shown by creatinine in the bivariate analysis of AGEs levels in the whole sample [ 21 ]. We discussed if that trend could have a fictitious origin since patients with SLE had higher creatinine levels (although in normal range) and were mostly located in the third AGEs tertile, and also since the trend was not observed when we analyzed the two groups separately.…”

Interstitial Lung Disease in Systemic Lupus Erythematosus and Systemic Sclerosis: How Can We Manage the Challenge?

“…ILD can determine severe clinical symptoms, worsening survival rates in these patients [2]. The relationship between ILD and SLE is relatively rare [2][3][4][5][6]. However, individuals with overlapping connective tissue disease syndromes are highly prone to develop this manifestation [2].…”

“…The identification of specific phenotypes in the serum of SLE patients who develop ILD and/on myositis was the objective of a recent study. Cotton et al showed that KL-6, anti-Ro52, and anti-Ku were the most prevalent antibodies in patients with ILD/myositis [3].…”