Temporal Correlations of Skin and Blood Metabolites with Clinical Outcomes of Biologic Therapy in Psoriasis

Abstract

Background Psoriasis is an inflammatory skin disease causing multisystem effects. Introduction of biologic drugs has led to promising results in treatment of this disease. Here, we carry out time-dependent profiling of psoriasis-related putative metabolic biomarkers. Methods Skin excretion specimens were collected from 17 patients with psoriasis treated with biologics for 7 months. Blood specimens were obtained from the same patients at intervals of 1–3 months. A hydrogel micropatch sampling technique was implemented to collect lesional (L) and nonlesional (NL) skin specimens. The collected skin and blood specimens were analyzed by mass spectrometric methods. Results The metabolites present on L skin—in particular, choline, and citrulline—showed greater dynamics, corresponding to the resolution of psoriasis than the metabolites present in NL skin or blood. Choline levels in L skin and blood correlated positively, while citrulline correlated negatively with the severity of individual psoriasis plaques and general disease severity, respectively. Nevertheless, the correlations between the metabolite levels in blood and general disease severity were weaker than those between the metabolite levels on L skin and severity of individual plaques. The changes of these skin metabolites were more prominent in the responders to the treatment than in the nonresponders. Conclusions The results support the feasibility of characterizing dynamic changes in psoriatic skin metabolic profiles with the hydrogel micropatch probes and mass spectrometric tests. The study represents one of few attempts to explore relationships between skin and blood metabolite concentrations. However, practical use of the methodology in close clinical monitoring is yet to be demonstrated.

Metabolomics Studies in Psoriatic Disease: A Review

“…While a few studies have examined the metabolite profiles of patients with autoimmune diseases (ADs) [9,10], or immunemediated inflammatory diseases (IMIDs) with no emphasis on Ps or PsA specifically [11], the majority of studies included in this review sought to identify metabolites that were associated with Ps by investigating Ps patients in comparison to healthy volunteers [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. Other studies focused on identifying metabolite profiles in Ps patients and correlating them with different measurements of disease activity [13,19,22,28,32,33]. Another important question in psoriatic disease that has garnered much interest pertains to determining which Ps patients have or will develop PsA.…”

“…Most studies included in our literature search were non-hypothesis driven and therefore employed an untargeted metabolomics approach [12,[14][15][16][19][20][21][22][23]25,26,[31][32][33]36,41,42]. However, there were several studies that analyzed specific metabolites using a targeted metabolomics approach [9,10,13,18,24,27,28,30,39,40].…”

“…Comparing metabolites across multiple sample matrices may provide additional information about their role in the disease given their distribution in various sample types. As such, a few studies analyzed both the skin and blood metabolome [29,30,33].…”

“…Protein precipitation (PPt) is another widely used sample preparation method for biological fluids that can sometimes be categorized as an LLE method since it requires usually the addition of cold solvent to allow the precipitation of proteins from the sample, which are then effectively removed, leaving only the metabolites [44]. PPt shares many of the same benefits and limitations as LLE [44], and the majority of studies included in this review used PPt to isolate metabolites and prepare the sample before analysis [13,[15][16][17][19][20][21]29,30,32,33,36,39,40,42].…”

“…Unlike biological fluids, tissue sample harvesting and processing, are more involved and usually necessitate additional steps such as homogenization and/or lyophilization prior to use of any of the above-mentioned strategies [43]. A few studies exploring the skin metabolome used a specialized biocompatible hydrogel micropatch probe to sample skin [22,33].…”