# Serum Metabolomic Profiling Reveals Differences Between Systemic Sclerosis Patients with Polyneuropathy

## TL;DR

This study identifies unique metabolomic differences in systemic sclerosis patients with polyneuropathy compared to those without and healthy controls.

## Contribution

The first study to examine metabolic changes in systemic sclerosis patients with polyneuropathy.

## Key findings

- SSc patients showed reduced levels of aspartic acid, glutamic acid, valine, and citrulline compared to healthy controls.
- SSc patients with PNP had elevated kynurenine, asparagine, and alanine levels distinct from other SSc patients.
- Metabolomic profiles suggest SSc patients with PNP form a distinct subgroup.

## Abstract

Metabolome studies have already been carried out in patients with systemic sclerosis (SSc). However, polyneuropathy (PNP) as a complication of SSc has been overlooked in these studies. To the best of our knowledge, this is the first study to examine metabolic changes in SSc patients with PNP. Patients with SSc (n = 62) and a healthy control group (HC) (n = 72) were recruited from two Latvian hospitals. Blood plasma samples were collected and analyzed using an LC-MS-based targeted metabolomics workflow. Our plasma sample cohort consisted of 62 patients with SSc, 42% of whom had PNP. Differences between SSc patients and the HC group with fold changes > 2 were observed for aspartic acid, glutamic acid, valine, and citrulline, all of which were reduced. In contrast to the SSc to HC discrimination, no metabolites had a high fold change; only minor changes were observed using FC > 1.3. We identified elevated concentrations of kynurenine, asparagine, and alanine. Changes in metabolite regulation in patients with SSc, compared to controls, are not identical to those observed in SSc patients with PNP, with elevated concentrations of kynurenine and alanine specific to the SSc subgroup. SSc patients with PNP should probably be considered a distinct population with important metabolomic features.