Targeted Metabolomics Investigation of Serum Levels of Fatty Acid Metabolites in Pemphigus Vulgaris Patients and Healthy Individuals Publisher



Saberi F ; Esmaili N ; Rezadoost H ; Karimi M ; Shakeri M ; Aryanian Z ; Ebrahimpour S ; Hosseini F ; Ghaseminia F
Source: Archives of Dermatological Research Published:2026

Abstract

Background: Pemphigus vulgaris (PV) is an autoimmune blistering disease involving mucous membranes and skin. Metabolomics, the study of small-molecule metabolite profiles, has led to significant understanding of disease pathogenesis. Serum levels of free fatty acid (FFA) metabolites play a crucial role in gene expression, protein production, immune system activity, and growth regulation. Materials and methods: We investigated serum free fatty acid (FFA) metabolite profiles in 26 newly diagnosed untreated PV patients and 24 age- and sex-matched healthy controls. Serum samples were processed and examined using gas chromatography with flame-ionization detection (GC-FID) after derivatization to fatty acid methyl esters. Although 28 metabolites were initially targeted; only 10 metabolites (methyl caprate, methyl laurate, methyl 11-dodecenoate, methyl myristate, methyl myristoleate, methyl palmitate, methyl stearate, methyl oleate, methyl linoleate, methyl arachidonate) were consistently detected above the lower limit of detection (LOD ~ 0.1–1 µM, depending on chain length). This reflects the sensitivity constraints of GC-based lipidomic in complex biological samples. Disease severity in PV group was assessed using the pemphigus disease area index (PDAI), and serum levels of anti-desmoglein 1 and 3 (anti-Dsg1, anti- Dsg3) antibodies were measured. Result: The study included 26 PV patients and 24 healthy controls, with no significant differences in demographic features or comorbidities between groups. PDAI scores ranged from 1 to 44, with 38.5% of patients classified as moderate and the remainder as mild. Mean serum anti-Dsg1 and anti-Dsg3 levels were 26.8 ± 31.2 U/mL and 101.5 ± 81.0 U/mL, respectively. Anti-Dsg3 levels showed significant positive correlations with methyl caprate (p = 0.008, r = 0.638), methyl laurate (p = 0.01, r = 0.573), and methyl myristate (p = 0.012, r = 0.487). However, the levels of methyl palmitate (33.61 vs. 43.55; p = 0.001) and methyl linoleate (12.34 vs. 17.19; p = 0.002) were significantly reduced in PV patients compared with controls. Conclusion: The positive correlation between serum anti-Dsg3 and levels of medium-chain saturated fatty acids (MCSFAs) such as methyl caprate and methyl laurate, as well as long-chain saturated fatty acids (LCSFAs) levels like methyl myristate, represents a novel finding that highlights the necessity for additional research in this field among PV patients. Alterations in serum levels of methyl palmitate and methyl linoleate and methyl myristate, may impact inflammation pathways in PV. Future studies may explore whether dietary modulation could influence outcomes. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2026.