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Severity of systemic sclerosis-associated interstitial lung disease linked to adipokine level

Reduced pulmonary function in systemic sclerosis-associated interstitial lung disease was linked to higher levels of an adipokine biomarker.

Systemic sclerosis can be defined as a systemic connective tissue disease. It is characterised by small vessel vasculopathy, production of autoantibodies and dysfunctional fibroblasts, with an increased deposition of extracellular matrix. In a UK study, the prevalence of systemic sclerosis was estimated to be 19.4 per million person-years and 4.7 times more common in women. In contrast, a US study estimated prevalence of 50 – 300 cases per million. Clinically, patients present with skin thickening, Raynaud’s syndrome and polyarthralgia. Fibrosis of the lung is known to be a complication of systemic sclerosis, leading to systemic sclerosis-associated interstitial lung disease (SS-ILD) and pulmonary hypertension. The presence of system sclerosis reduces life-expectancy by 16 to 34 years and studies suggest that SS-ILD is associated with a 2.6 greater increased risk of death. However, there is a lack of data on potential biomarkers of lung function, hindering the assessment of current and future disease progression.

Some work has revealed an accumulation of myofibroblasts in fibrotic skin in patients with systemic sclerosis and a loss of intradermal adipose tissue. Furthermore, patients with systemic sclerosis have been found to have lower levels of serum adiponectin, a hormone secreted by adipose tissue. Other data has suggested that one particular adipokine, CTRP9 is elevated in patient with patients with systemic sclerosis. This led a team from the Department of Medicine, Division of Rheumatology, University of California, US, to examine whether CTRP9 could serve as a biomarker with predictive valve for pulmonary function in patients with SS-ILD. The team turned to a patient registry to retrospectively examine this relationship and included patients with documented pulmonary tests over a 48-month interval and where CTRP9 levels had been initially recorded. They split patients into a high and low group according to CTRP9 levels and set the primary outcome of interest as forced vital capacity percent predicted (FVC%), which is valid measure of disease severity in SS-ILD.

A total of 61 patients with a mean age of 53.5 years (77.3% female) were included in the analysis. Elevated circulating CTRP9 levels were associated with significantly lower FVC% levels at baseline (72% vs 80%, p = 0.02) and after 48 months (68% vs 84%, p = 0.001). In addition, the researcher sought to determine whether CTRP9 levels could predict disease stability, which they defined as less than 3% decrease in FVC% over 48 months. The analysis showed that a low baseline CTRP9 level had a sensitivity of 73% and a specificity of 45% for disease stability.

The authors discussed how their findings clearly indicated that the presence of elevated CTRP9 was associated with more severe lung disease. They concluded that CTRP9 could represent a prognostic biomarker and a possible therapeutic target for SS-ILD.

Yang MM et al. Circulating CTRP9 is associated with severity of systemic sclerosis-associated interstitial lung disease. Arthritis Care Res 2021