Table 1.
Previously performed proteomic studies in psoriasis.
| Year | Author/Reference | Proteomics Methodology | Samples | Patients | Key Findings |
|---|---|---|---|---|---|
| 2005 | Carlén et al. [10] | 2D-electrophoresis, MALDI-TOF MS, Q-TOF-MS/MS | Skin | Psoriasis patients: lesional skin—7 samples; normal-looking skin—3 samples); patients with acute glutate psoriasis: lesional skin—6 samples; normal-looking skin—5 samples; healthy individuals—4 samples. | The first known proteomic study of lesional psoriatic skin; the first comparative analysis of patients with plaque psoriasis and acute guttate psoriasis. |
| 2007 | Bonnekoh et al. [11] | Multi-epitope ligand cartography (MELC) robot technology | Skin | Psoriasis patients: 6 samples of lesional skin; healthy volunteers 6 samples of healthy skin. | The authors showed a significant diversity in location of inflammatory epitopes after immunotherapy with efalizumab. They proposed CD138 and TRF1/CD71 as prognostic biomarkers of treatment outcome with efalizumab. |
| 2007 | Plavina et al. [12] | M-LAC coupled with LC-MS/MS | Serum | Psoriasis patients—20; healthy volunteers—20. | Depletion of immunoglobulins and albumin revealed upregulation of cytoskeletal and actin-binding proteins in plasma of psoriasis undetectable in regular serum. |
| 2008 | Plavina et al. [13] | M-LAC coupled with LC-MS/MS; ultracentrifugation followed by bynano LC-MS/MS | Serum | Psoriasis patients—20; healthy volunteers—20. | The authors identified 21 DEPs previously associated with other autoimmune disorders (e.g., thymosin β4, talin 1, γ-actin, filamin, profilin, S100A8, and S100A9) in serum of psoriasis patients. These DEPs were previously undetectable in the serum due to a higher abundance of immunoglobulins and serum albumin. |
| 2011 | Ryu et al. [14] | 2D-electrophoresis, nanoLC-MS/MS | Two pools of skin samples (n = 8 and 28) | Psoriasis patients, 36 paired samples of lesional and normal-looking skin. | One of the first comparative analyses of lesional and normal-looking skin; the first known ontology analysis of DEPs in psoriatic skin. |
| 2010 | Piruzian et al. [15] | 2D-electrophoresis, nanoLC-MS/MS | Pooled skin samples | Psoriasis patients, 3 paired samples of lesional and normal-looking skin. | The authors reported of the 10 most upregulated proteins in lesional skin. |
| 2013 | Schonthaler et al. [16] | iTRAQ-2DLC-MS/MS | Epidermis | Psoriasis patients, 19 paired samples of lesional and normal-looking skin. | The authors identified S100A8, S100A9, and complement C3 as the three most upregulated proteins in lesional skin: they also showed that knocking S100A9 out in JunB-Jun double knockout mice attenuated psoriasis-like skin disorder. |
| 2013 | van Swelm et al. [17] | MALDI-TOF MS | Urine | Psoriasis patients—60, with and without liver fibrosis | The authors proposed ITIH4 and CDH2 as candidate biomarkers of methotrexate-induced hepatic fibrosis in psoriasis patients. |
| 2013 | Williamson et al. [18] | Dimethyl labelling, LTQ-Orbitrapnano LC-MS/MS | Skin and serum | Psoriasis patients—4 paired samples of lesional and normal-looking skin; 4 samples of blood plasma; commercial blood plasma of healthy donors (n = 2). | The authors identified several dozen DEPs comparing lesional vs. normal-looking skin of psoriasis patients: they also proposed profilin as a biomarker of psoriasis. |
| 2014 | Fattahi et al. [19] | MALDI/TOF-TOF | Serum | Psoriasis patients—20; and 16 healthy volunteers. | The authors found a lower abundance of retinol-binding protein RBP4, a higher abundance of KRT10 and the unique expression pattern of α1 antitrypsin isoforms in sera of psoriasis patients. |
| 2015 | Cretu et al. [20] | LC-MS/MS | Pooled skin samples (n = 5) | Psoriasis patients with and without psoriatic arthritis (10 patients in each group), samples of lesional and normal-looking skin. | The authors proposed ITGB5 as a potential biomarker of psoriatic arthritis in psoriasis patients. |
| 2015 | Swindell et al. [21] | Label-free LC-MS/MS, LTQ-Orbitrap nanoLC-MS/MS | Skin | Psoriasis patients—14 paired samples of lesional and normal-looking skin. | The first known “bi-omic study” of psoriatic skin. The authors identified 748 DEPs in lesional and normal-looking psoriatic skin. They also discovered a modest correlation between protein and gene expression in psoriasis patients and characterized the role of IL-17A in disease-associated gene expression. |
| 2016 | Reindl et al. [22] | LTQ-Orbitrap nanoLC-MS/MS | Serum | Psoriasis patients—6; healthy volunteers—6. | The authors proposed AZGP1, complement C3, polymeric immunoglobulin receptor PIGR, and plasma kallikrein KLKB1 as disease-associated biomarkers. They discovered a moderate correlation between disease severity and the expression of DSP, complement C3, PIGR, and KRT17. |
| 2017 | Brunner [23] | Proximity extension assay | Serum | Patients with atopic dermatitis—59; psoriasis patients—22. | The authors found that inflammatory potential in patients with atopic dermatitis is higher than in psoriasis patients. They also showed a higher risk of cardiovascular disorders in both groups of patients. |
| 2017 | Kolbinger et al. [24] | Proximity extension assay | Serum, skin and dermis | Psoriasis patients—8 paired samples of lesional and normally-looking skin; healthy volunteers 8 skin samples; blood serum of the same individuals. | The authors showed how increased expression of antimicrobial peptides, proinflammatory cytokines and neutrophil chemoattractants normalizes in psoriasis patients after their treatment with secukinumab. They also proposed DEFB4 as a biomarker of the therapeutic response. |
| 2017 | Matsuura et al. [25] | MALDI-TOF MS, TripleTOF-MS/MS | Serum | Psoriasis patients with and without psoriatic arthritis (n = 10 and 24, respectively); 14 patients with atopic dermatitis; 23 healthy volunteers. | The authors identified several psoriasis/psoriatic arthritis associated DEPt originated from FGA, FLG, TMSB4X, and FLJ55606 in the sera of psoriasis patients. |
| 2017 | Méhul et al. [26] | qTOF-MS/MS and protein array | Stratum corneum | 40 paired samples stripped from lesional and normal-looking skin of psoriasis patients. | The first comparative study of stratum corneum of psoriasis patients; the authors proposed 21 candidate biomarkers of lesional psoriatic stratum corneum. |
| 2017 | Méhul et al. [27] | qTOF-MS/MS and protein array | Stratum corneum | Patients with CTCL—10; psoriasis patients—24 (paired samples of stratum corneum stripped from lesional and normal-looking skin). | The first comparative proteomic study of patients with psoriasis and CTCL. The authors established a molecular signature of 112 DEPs to distinguish the samples of psoriasis patients and patients with CTCL. |
| 2017 | Wang et al., [28] | SomaScan | Serum | Patients with atopic dermatitis—20; patients with contact dermatitis—10; patients with atopic and contact dermatitis—10; psoriasis patients—12. | The authors reported 4 DEPs, namely KYNU, LG3BP, TPSB2, and CA6 associated with psoriasis and proposed KYNU as a disease-associated biomarker. |
| 2018 | Gęgotek et al. [29] | GeLC-MS/MS, LTQ Orbitrap-nanoLC-MS/MS | Serum | Psoriasis patients—6; healthy volunteers—6. | The authors detected a higher level of adducts in plasma of psoriasis patients. They also found a decreased level of vitamin D and proteins involved in lipid metabolism. In addition, they demonstrated higher abundance of proteins involved in immune response and signal transduction. |
| 2018 | Kim et al. [30] | Proximity extension assay | Serum | Psoriasis patients—266. | The authors discovered the strongest correlation between PASI and the expression levels of IL17A and IL17C, IL20, and CCL20 among the reponders to tofacitinib. |
| 2018 | Li et al. [31] | TMT labeling, LC-MS/MS | PBMC | New onset psoriasis patients (n = 31) and healthy volunteers (n = 32). | The authors identified new disease-associated proteins, namely ATM, SLFN5, ZNF512, SPATA13, DOCK2, ARSB, VIRMA, and NRGN. |
| 2019 | Foulkes et al. [32] | SomaScan | Serum | Psoriasis patients—10. | The authors reported increased expression of TNF- and interferon-dependent proteins. |
| 2019 | Garshick et al. [33] | Proximity extension assay | Serum and endothelial cells of brachial vein | Psoriasis patients—20. | The authors established a molecular signature of 8 DEPs, namely IL1β, CXCL10, VCAM-1, IL-8, CXCL1, LTB, ICAM-1, and CCL3, that characterizes the risk of atherosclerosis in psoriasis patients. They also discovered a correlation of the named biomarkers and PASI. In addition, they proposed an existence of a mechanism that damages different tissues in psoriasis. |
| 2019 | Gęgotek et al. [34] | GeLC-MS/MS, LTQ Orbitrap-nanoLC-MS/MS | Keratino-cytes and lympho-cytes | Psoriasis patients—6; healthy volunteers—6. | The authors discovered a higher level of adducts in plasma, skin and primary cells of psoriasis patients, lower expression of TXNRD1, higher expression of the glycolytic isoenzymes, namely PGAM1 and -2. |
| 2019 | Ge et al. [35] | UPLC-MS/MS with Q-Exactive Plus Hybrid Quadrupole-Orbitrap | Pooled skin samples (n = 15) | Psoriasis patients—45 paired samples of lesional and normal-looking skin. | The first study presenting a comprehensive analysis of 2-hydroxyisobutyrylation in lesional and normal-looking skin of psoriasis patients. |
| 2019 | Szél, E. et al. [36] | 2D-electrophoresis, LC-MS/MS | Skin | Psoriasis patients—3 paired samples of lesional and normal-looking skin; healthy volunteers—3 skin samples, | The authors reported ~30 DEPs previously not associated with the disease. They also proposed PRKDC and MYBBP1A as potential key regulators of hyperproliferation and altered differentiation of skin cells, stress, and immune response in psoriasis, |
| 2019 | Xu et al. [37] | Custome-made array of specific antibodies directed to disease associated biomarkers, DIA-MS | Serum | Psoriasis patients—16; healthy volunteers—23, | The authors designed and tested a custom-made array of antibodies specific to 112 previously discovered disease-associated biomarkers. They also found a moderate correlation of PASI and the expression of PI3, CCL22, and IL12B. In addition, they proposed three predictive biomarkers, namely FCN2, MIF, and MMP1, to identify the responders to the traditional Chinese medicine YinXieLing. |
| 2020 | Medvedeva et al. [38] | Proximity extension assay | Serum | Psoriasis patients—150. | The authors proposed IL17A and KLK7 as biomarkers of disease severity and they also established the molecular signature of 4 DEPs, namely KLK7, PEDF, MDC, and ANGPTL4, to predict the outcome of the therapy to apremilast. |
| 2020 | Gęgotek et al. [39] | GeLC-MS/MS, LTQ Orbitrap-nanoLC-MS/MS | Fibroblasts | Psoriasis patients—5 samples of lesional skin; healthy volunteers—6 skin samples. | The authors discovered a higher abundance of TXNRD1 and a lower abundance of several glycolytic enzymes (PK, PGK2, ALDOL, and GAPDH) in dermal fibroblasts. |
| 2020 | Li et al. [40] | TMT labeling, LC-MS/MS | Skin | Psoriasis patients—11 samples of lesional skin; healthy volunteers—11 skin samples. | The authors identified 9 DEPs previously not associated with psoriasis: MPO, TYMP, IMPDH2, GSTM4, and ALDH3A1 that were upregulated and CES1, MAOB, MGST1, and GSTT1—that were downregulated in lesional skin. |
| 2020 | Zhou et al. [41] | iTRAQ-Labeling, LC-MS/MS | Skin and serum | Psoriasis patients—16 paired samples of lesional and normal-looking skin; 32 blood samples; healthy volunteers—15 skin samples and 24 blood samples. | The authors identified 4 new proteins, namely OAS2, IFIT3, IRF3, and MeCP2, previously not associated with psoriasis, and proposed OAS2 as a disease-associated biomarker to analyze both skin and sera samples. They also presented an optimized protocol for the obtaining of skin samples and their processing. |
| 2021 | Elnabawi et al. [42] | Proximity extension assay | Endothe-lial cells of brachial vein and serum | Psoriasis patients—23; healthy volunteers—10. | The authors found that the expression of CCL20 and IL6 correlates with LDL-cholesterol, endothelial inflammation score and PASI. They proposed CCL6 as a biomarker of impaired vascular health in psoriasis patients. |
| 2021 | Glickman et al. [43] | Proximity extension assay | Serum | Patients with moderate-to-severe alopecia areata (n = 35), atopic dermatitis (n = 49), moderate-to-severe psoriasis (n = 19) and healthy volunteers (n = 36). | The authors found that patients with the advanced forms of alopecia areata exhibit the highest systemic inflammatory tone and higher expression of cardiovascular risk biomarkers compared to the other groups of patients and their fellow groupmates without total involvement. They presented evidence that alopecia areata is a systemic disorder. |
| 2021 | Kaiser et al. [44] | Proximity extension assay | Serum | Psoriasis patients with and without the signs of atherosclerosis—85. | The authors discovered a negative correlation of GDF15 and vascular inflammation in the ascending aorta and entire aorta. They found that the expression of GDF15 positively correlates with carotid intima-media thickness and coronary artery calcium score in psoriasis patients without cardiovascular disease and statin treatment. |
| 2021 | Leijten et al. [45] | Proximity extension assay | Serum | Psoriasis patients with and without psoriatic arthritis (n = 20 and 18, respectively); healthy volunteers (n = 19). | The authors discovered strong correlations of joint swollenness and the expression levels of of ICAM-1 and CCL18. They also found a strong correlation of PASI and the expression of PI3 and IL17RA. |
| 2021 | Navrazhina et al. [46] | Proximity extension assay | Serum | Patients with moderate-to-severe hidradenitis suppurativa (n = 11), patients with psoriasis (n = 10) and healthy volunteers (n = 10). | The authors discovered that patients with hidradenitis suppurativa exhibited a significantly more intense inflammatory burden and an increase in cardiovascular/atherosclerosis-related biomarkers than psoriasis patients. They also proposed a computer model to distinguish sera samples of patients with hidradenitis suppurativa and psoriasis. |
| 2021 | Sobolev et al. [47] | LC-MS/MS | Skin | Psoriasis patients—5 paired samples of lesional and normal-looking skin; healthy volunteers—5 skin samples. | The authors proposed an existence of two adaptive mechanisms in normal-looking skin aimed to modulate there the development of the inflammatory response and accelerate the protein metabolism in the diseased cells, respectively. They reported a suppression of kallikrein-kinin system in normal-looking skin. |
| 2021 | Sobolev et al. [48] | LC-MS/MS | Skin | Psoriasis patients—5 paired samples of lesional and normal-looking skin; healthy volunteers—5 skin samples. | The authors discovered a set of 6 estrogen-dependent DEPs that modulate psoriasis in female skin. They proposed an existence of adaptive mechanism in female patients that facilitates the disease flow. |
| 2021 | Wang et al. [49] | TMT labeling, LC-MS/MS | pooled skin samples (n = 15) | Psoriasis patients—30 paired samples of lesional and normal-looking skin; healthy volunteers—30 skin samples. | The study compared psoriasis patients of Chinese and Caucasian descent pointing to the differences in protein expression in both populations. They identified GSTP1, SFN, KRT77, FLG2, and TREX2 as DEPs differentially expressed in Caucasians and SIRT1—as differentially expressed in Chinese patients. |
| 2021 | Zue et al. [50] | iTRAQ-Labeling, LC-MS/MS | PBMC | Two groups of 4 psoriasis patients with and without psoriatic arthritis. | The authors proposed SIRT2 as a potential biomarker of psoriatic arthritis in psoriasis patients. |
| 2022 | Navrazhina et al. [51] | Proximity extension assay | Skin | Patients with hidradenitis suppurativa—13 paired samples of lesional and normal-looking skin; psoriasis patients—11 paired samples of lesional and normal-looking skin; healthy individuals—11 skin samples. | The authors found that skin inflammation in the patients with hidradenitis suppurativa extends far beyond the skin lesions and sustains on a comparable level. They provided evidence that hidradenitis suppurativa is a systemic disorder. |