Abstract
Systemic sclerosis (SSc) is a severe multi-organ disease with interstitial lung disease (ILD) being the major cause of death. While targeted therapies are emerging, biomarkers for sub-stratifying patients based on individual profiles are lacking. Herein, we investigated how levels of serum metabolites correlated with different stages of SSc and SSc-ILD. Serum samples of patients with SSc without ILD, stable and progressive SSc-ILD as well as of healthy controls (HC) were analysed using liquid targeted tandem mass spectrometry. The best discriminating profile consisted of 4 amino acids (AA) and 3 purine metabolites. l-tyrosine, l-tryptophan, and 1-methyl-adenosine distinguished HC from SSc patients. l-leucine, l-isoleucine, xanthosine, and adenosine monophosphate differentiated between progressing and stable SSc-ILD. In SSc-ILD, both, l-leucine and xanthosine negatively correlated with changes in FVC% predicted. Additionally, xanthosine was negatively correlated with changes in DLco% predicted and positively with the prognostic GAP index. Validation of l-leucine and l-isoleucine by an enzymatic assay confirmed both the sub-stratification of SSc-ILD patients and correlation with lung function and prognosis score. Serum metabolites may have potential as biomarkers for discriminating SSc patients based on the presence and severity of ILD. Confirmation in larger cohorts will be needed to appreciate their value for routine clinical care.
Highlights
Systemic sclerosis (SSc) is a severe multi-organ disease with interstitial lung disease (ILD) being the major cause of death
Serum metabolite profiling yielded a final set of 4 amino acids and 3 purine metabolites
As previously observed in lung fibrosis and SSc14, there was a tendency towards lower adenosine monophosphate (AMP) levels in progressing SSc-ILD patients
Summary
Systemic sclerosis (SSc) is a severe multi-organ disease with interstitial lung disease (ILD) being the major cause of death. Validation of l-leucine and l-isoleucine by an enzymatic assay confirmed both the sub-stratification of SSc-ILD patients and correlation with lung function and prognosis score. Serum metabolites may have potential as biomarkers for discriminating SSc patients based on the presence and severity of ILD. Disease severity at time point of ILD diagnosis and progression over time determine the prognosis[2,4,5] Available measures such as imaging, pulmonary function tests, or patient reported outcome scores have been shown to be of limited predictive value for the identification of SSc-ILD patients with poor p rognosis[6,7]. Diagnostic potential since SSc patients could be distinguished from healthy controls based on their serum and/ or urine metabolome with alterations in hexose, glycerolipid, and amino acid m etabolism[21,22]
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