Dataset Information

Metabolomics in psoriatic disease: pilot study reveals metabolite differences in psoriasis and psoriatic arthritis.

ABSTRACT:

Importance

While "omics" studies have advanced our understanding of inflammatory skin diseases, metabolomics is mostly an unexplored field in dermatology.

Objective

We sought to elucidate the pathogenesis of psoriatic diseases by determining the differences in metabolomic profiles among psoriasis patients with or without psoriatic arthritis and healthy controls.

Design

We employed a global metabolomics approach to compare circulating metabolites from patients with psoriasis, psoriasis and psoriatic arthritis, and healthy controls.

Setting

Study participants were recruited from the general community and from the Psoriasis Clinic at the University of California Davis in United States.

Participants

We examined metabolomic profiles using blood serum samples from 30 patients age and gender matched into three groups: 10 patients with psoriasis, 10 patients with psoriasis and psoriatic arthritis and 10 control participants. Main outcome(s) and measures(s): Metabolite levels were measured calculating the mean peak intensities from gas chromatography time-of-flight mass spectrometry.

Results

Multivariate analyses of metabolomics profiles revealed altered serum metabolites among the study population. Compared to control patients, psoriasis patients had a higher level of alpha ketoglutaric acid (Pso: 288 ± 88;

Control

209 ± 69; p=0.03), a lower level of asparagine (Pso: 5460 ± 980;

Control

7260 ± 2100; p=0.02), and a lower level of glutamine (Pso: 86000 ± 20000;

Control

111000 ± 27000; p=0.02). Compared to control patients, patients with psoriasis and psoriatic arthritis had increased levels of glucuronic acid (Pso + PsA: 638 ± 250;

Control

347 ± 61; p=0.001). Compared to patients with psoriasis alone, patients with both psoriasis and psoriatic arthritis had a decreased level of alpha ketoglutaric acid (Pso + PsA: 186 ± 80; Pso: 288 ± 88; p=0.02) and an increased level of lignoceric acid (Pso + PsA: 442 ± 280; Pso: 214 ± 64; p=0.02).

Conclusions and relevance

The metabolite differences help elucidate the pathogenesis of psoriasis and psoriatic arthritis and they may provide insights for therapeutic development.

SUBMITTER: Armstrong AW

PROVIDER: S-EPMC4288418 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Metabolomics in psoriatic disease: pilot study reveals metabolite differences in psoriasis and psoriatic arthritis.

Armstrong April W AW Wu Julie J Johnson Mary Ann MA Grapov Dmitry D Azizi Baktazh B Dhillon Jaskaran J Fiehn Oliver O

F1000Research 20141021

<h4>Importance</h4>While "omics" studies have advanced our understanding of inflammatory skin diseases, metabolomics is mostly an unexplored field in dermatology.<h4>Objective</h4>We sought to elucidate the pathogenesis of psoriatic diseases by determining the differences in metabolomic profiles among psoriasis patients with or without psoriatic arthritis and healthy controls.<h4>Design</h4>We employed a global metabolomics approach to compare circulating metabolites from patients with psoriasis ...[more]

PMID: 25580230

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Project description:BackgroundOxylipins are biological lipids that have been implicated in inflammation. We previously found that certain oxylipins correlated with clinical manifestations in psoriatic arthritis (PsA) patients. Here, we compare oxylipin profiles in PsA patients and those with psoriasis (PsO) without inflammatory arthritis to identify oxylipins that associate with specific disease manifestations to better understand disease pathogenesis and identify new biomarkers.MethodsConsecutive patients with PsA (who met the CASPAR classification criteria for PsA) and PsO were recruited from the Rheumatology Outpatient Clinic. A thorough clinical examination was performed, including entheseal (Leeds enthesitis index (LEI)) and joint involvement (SJC/TJC 66/68). Patients were evaluated for pain and global disease activity on a visual analog scale (VAS) ranging from 0 to 100. This was followed by disease activity scores calculation: cDAPSA (Disease Activity Index for Psoriatic Arthritis) and Psoriasis Area and Severity Index (PASI). Serum oxylipins were determined by mass spectrometry and their association with clinical characteristics (PASI/LEI and cDAPSA) was analyzed using Metaboanalyst 4.0 and R version 3.6.1.ResultsTwenty PsO (average age 52 [10.8], 55% males) and 19 PsA patients (average age 60.5 [11.4], 63.1% males) were included. PsO patients had an average body mass index (BMI) of 33.7 (6.84) and an average PASI of 3.8 (4.2). PsA patients had an average BMI of 31.9 (5.6), TJC of 9.3 (10.41), SJC of 3.7 (4.23), with an average cDAPSA of 23.3 (11.4). 63.1% of PsA patients had enthesitis (average LEI 2.2 [3]) and the same percentage had psoriasis (average PASI 3(5]). Sera were analyzed for oxylipin levels. PsO and PsA patients with higher PASI score (> 2.5) had significantly lower serum concentrations of pro-inflammatory oxylipins, most of them arachidonic acid derived (AA). Oxylipin profiling did not associate with cDAPSA. Interestingly, several AA-derived oxylipins (5,15 di-HETE (5S,15S-dihydroxy-6E,8Z,10Z,13E-eicosatetraenoic acid), 5-oxoETE (5-Oxo-eicosatetraenoic acid), PGE2 (prostaglandin E2), 11bPGE2 (11 beta prostaglandin D2), and LTB4 (leukotriene B4)) were significantly increased in PsA patients with enthesitis compared to those without.ConclusionsThe AA-derived proinflammatory oxylipins were lower in both PsO and PsA patients with higher skin scores. Joint disease activity was not associated with the concentrations of oxylipins. Yet, enthesitis was associated with an increase of AA-derived pro-inflammatory oxylipins in PsA patients. Further studies are needed to determine whether oxylipin profiling can be a good biomarker of enthesitis in PsA patients.

Project description:A genome-wide association study was performed to identify genetic factors involved in susceptibility to psoriasis (PS) and psoriatic arthritis (PSA), inflammatory diseases of the skin and joints in humans. 223 PS cases (including 91 with PSA) were genotyped with 311,398 single nucleotide polymorphisms (SNPs), and results were compared with those from 519 Northern European controls. Replications were performed with an independent cohort of 577 PS cases and 737 controls from the U.S., and 576 PSA patients and 480 controls from the U.K.. Strongest associations were with the class I region of the major histocompatibility complex (MHC). The most highly associated SNP was rs10484554, which lies 34.7 kb upstream from HLA-C (P = 7.8x10(-11), GWA scan; P = 1.8x10(-30), replication; P = 1.8x10(-39), combined; U.K. PSA: P = 6.9x10(-11)). However, rs2395029 encoding the G2V polymorphism within the class I gene HCP5 (combined P = 2.13x10(-26) in U.S. cases) yielded the highest ORs with both PS and PSA (4.1 and 3.2 respectively). This variant is associated with low viral set point following HIV infection and its effect is independent of rs10484554. We replicated the previously reported association with interleukin 23 receptor and interleukin 12B (IL12B) polymorphisms in PS and PSA cohorts (IL23R: rs11209026, U.S. PS, P = 1.4x10(-4); U.K. PSA: P = 8.0x10(-4); IL12B:rs6887695, U.S. PS, P = 5x10(-5) and U.K. PSA, P = 1.3x10(-3)) and detected an independent association in the IL23R region with a SNP 4 kb upstream from IL12RB2 (P = 0.001). Novel associations replicated in the U.S. PS cohort included the region harboring lipoma HMGIC fusion partner (LHFP) and conserved oligomeric golgi complex component 6 (COG6) genes on chromosome 13q13 (combined P = 2x10(-6) for rs7993214; OR = 0.71), the late cornified envelope gene cluster (LCE) from the Epidermal Differentiation Complex (PSORS4) (combined P = 6.2x10(-5) for rs6701216; OR 1.45) and a region of LD at 15q21 (combined P = 2.9x10(-5) for rs3803369; OR = 1.43). This region is of interest because it harbors ubiquitin-specific protease-8 whose processed pseudogene lies upstream from HLA-C. This region of 15q21 also harbors the gene for SPPL2A (signal peptide peptidase like 2a) which activates tumor necrosis factor alpha by cleavage, triggering the expression of IL12 in human dendritic cells. We also identified a novel PSA (and potentially PS) locus on chromosome 4q27. This region harbors the interleukin 2 (IL2) and interleukin 21 (IL21) genes and was recently shown to be associated with four autoimmune diseases (Celiac disease, Type 1 diabetes, Grave's disease and Rheumatoid Arthritis).

Dataset Information

Metabolomics in psoriatic disease: pilot study reveals metabolite differences in psoriasis and psoriatic arthritis.

Importance

Objective

Design

Setting

Participants

Results

Control

Control

Control

Control

Conclusions and relevance

Publications

Metabolomics in psoriatic disease: pilot study reveals metabolite differences in psoriasis and psoriatic arthritis.

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