Decreased serum cathepsin S levels in patients with systemic sclerosis‐associated interstitial lung disease

Abstract

Cathepsin S (CTSS) is a lysosomal proteolytic enzyme regulating intracellular and extracellular biological activities, including immunity/inflammation and remodeling of vasculature and extracellular matrix, which are the three cardinal pathological events associated with systemic sclerosis (SSc). To elucidate the potential role of CTSS in the development of SSc, we investigated the clinical correlation of serum CTSS levels. Because serum CTSS levels were inversely correlated with estimated glomerular filtration rate (eGFR) in SSc patients with renal dysfunction (eGFR, <60 min/mL per 1.73 m2), SSc patients with normal renal function (eGFR, ≥60 min/mL per 1.73 m2) were analyzed. Serum CTSS levels were significantly decreased in diffuse cutaneous SSc patients compared with limited cutaneous SSc patients and healthy controls. Among vascular and fibrotic clinical manifestations, Raynaud’s phenomenon and interstitial lung disease (ILD) were relevant to a significant decrease in serum CTSS levels. Importantly, serum CTSS levels negatively correlated with serum levels of Krebs von den Lungen‐6 and surfactant protein D in total SSc patients, while not correlating with modified Rodnan total skin thickness score and the percentage of predicted diffusion lung capacity for carbon monoxide and showing a positive trend with the percentage of predicted vital capacity. These results suggest a potential contribution of decreased CTSS expression to the development of ILD in patients with SSc.

One year in review 2021: systemic sclerosis

“…A recent study demonstrated that cathepsin S serum levels are significantly lower in SSc patients, especially those with diffuse cutaneous SSc (dcSSc), than in healthy controls. Moreover, reduced serum cathepsin S seems to strongly associate with SSc-ILD, since it also negatively correlated with other ILD biomarkers such as serum Krebs von den Lungen-6 (KL-6) (20). Protein convertase subtilisin/kexin type 9 (PCSK9), a molecule linked with cholesterol metabolism, was found downregulated in SSc patients compared to controls and its serum levels directly correlated with carotid intima-media thickness.…”

“…• ECM and soluble factors in SSc microenvironment are gaining growing importance in SSc profibrotic activation (13,16,17,20).…”

Mucopolysaccharidosis Type IVA: Extracellular Matrix Biomarkers in Cardiovascular Disease

“…Cathepsin S has been associated with the pathogenesis of many conditions including but not limited to lung diseases ( 62 ), autoimmune diseases ( 56 , 57 , 63 , 64 ), CVD ( 36 , 65 ), type 2 diabetes ( 66 , 67 ), obesity ( 58 , 68 ), metabolic syndrome ( 55 ), neurodegenerative disease ( 69 ), and cancer ( 70 , 71 ). The majority of studies report elevated cathepsin S levels in association with the specific disease process, however, a recent study has reported decreased cathepsin S levels in patients with systemic sclerosis associated interstitial lung disease ( 72 ).…”

Identifying effective diagnostic biomarkers and immune infiltration features in chronic kidney disease by bioinformatics and validation

“…CD45/PTPRC (leukocyte common antigen/protein tyrosine phosphatase receptor type C) is a transmembrane glycoprotein expressed on almost all hematopoietic cells except mature red blood cells, and is an essential regulator of T and B cell antigen receptor-mediated activation (Al Barashdi et al, 2021). CTSS (cysteine protease cathepsin S) regulates biological activities in and out of cells, including immunity and inflammation (Toyama et al, 2020). There is evidence that CTSS may be beneficial in treating renal fibrosis.…”