Changes in plasma phospholipid metabolism are associated with clinical manifestations of systemic sclerosis

Geroldinger-Simić M, Bӧgl T, Himmelsbach M, Sepp N, and Buchberger W. (2021) Changes in plasma phospholipid metabolism are associated with clinical manifestations of systemic sclerosis. Diagnostics

Systemic sclerosis (SSc) is an autoimmune disease where fibrosis of the skin or internal organs occurs. Fibrosis is the result of connective tissue replacing normal parenchymal tissue when healing from a wound causing tissue remodeling and permanent scar tissue. Patients with SSc have reduced quality of life because of multi-organ manifestations of SSc including thickening of the skin, chronic digital ulcers, pain, superinfections due to calcinosis cutis, dyspnea due to lung disease, dry mouth, and dry eyes from sicca mucositis. SSc can be separated into two subsets: limited cutaneous SSc (lcSSc) where skin fibrosis is limited to distal extremities and face or diffuse cutaneous SSc (dcSSc) with generalized skin fibrosis. Interestingly, the lipidomic profile is different between the two subsets. Recently, more data has come out supporting a link between autoimmune and inflammatory diseases and lipid profile. This has been demonstrated in multiple sclerosis, systemic lupus erythematosus, rheumatoid arthritis, psoriasis, lyme arthritis, polymyositis, and dermatomyositis where all diseases are associated with a different lipidomic profile compared to controls. Since there is limited research studying the role of lipids in SSc, Geroldinger-Simić et al were interested in determining the phospholipid profile in patients with SSc and the differences between people with lcSSc and dcSSc.

In the study there were 48 controls without SSc and 52 patients with SSc. Of the 52 with SSc, 39 had lcSSc, 11 had dcSSc, and 2 did not have skin sclerosis likely because they were diagnosed with Very Early diagnosis of Systemic Sclerosis (VEDOSS). Plasma samples from the participants were analyzed for 263 targets and in patients with SSc, phosphatidylcholine with one acyl and one alkenyl side chain (PC ae) and sphingomyelin (SM) species were upregulated compared to the controls without SSc.

Geroldinger-Simić et al were interested in determining if there are lipidomic differences between lcSSc and dcSSc. They found that patients with dcSSc had significantly increased PC ae 32:0 species and a decrease in phosphotidylethanolamine with one acyl and one alkenyl side chain (PE ae) 38:5 and 38:6 species compared to the patients with lcSSc. As well, SM 30:1, 32:2, and 40:4 were significantly decreased in the patients with dcSSc.

To determine if plasmalogens and SM are associated with the presence of clinical symptoms in patients with SSc, the plasma lipid levels were compared along with their modified Rodnan skin score (mRSS). The mRSS is a standard measure for skin disease in SSc and is determined by summing the skin thickness of 17 different areas of the body producing a score ranging from 0 (if no areas have thickening) to 51 (if all areas have severe thickening). Patients with SSc scoring a high mRSS had significantly decreased SM and plasmalogens were increased compared to patients with low mRSS. In addition, the patients who experienced digital ulcers (DU) also had decreased levels of SM compared to the patients without DU. Calcinosis cutis was associated with decreased levels of plasmalogens and patients with lung fibrosis had significantly lower levels of phosphatidylethanolamine plasmalogens compared to the patients without lung fibrosis.

Geroldinger-Simić et al were interested in the lipidome of patients with SSc, whether there are differences between lcSSc and dcSSc, and if there is an association between lipid changes and clinical symptoms. They found that SM and plasmalogens are significantly changed in patients with SSc. Within the types of SSc, there are also distinct differences between lcSSc and dcSSc. People with the more severe form, dcSSc, also have increased PC ae and SM compared to lcSSc patients, which mirrors the difference seen between people with and without SSc. Plasmalogens have roles in inflammation and oxidative stress, therefore alterations to their levels can be used as biomarkers for the disease. Further work to determine if specific species have a causative role in the disorder or if plasmalogen replacement therapies can help reduce clinical symptoms or skin thickening would be beneficial in understanding SSc more.