Proteins in the Skin and Blood in Patients with Psoriasis: A Systematic Review of Proteomic Studies

Abstract

<b><i>Background:</i></b> Proteins play a central role in psoriasis as they are involved in the structural phenotypic changes and inflammation that characterize the disease. This systematic review aimed to assess which proteins have been consistently reported as upregulated or downregulated in the skin and blood from patients with psoriasis. <b><i>Methods:</i></b> We included proteomic studies reporting differentially expressed proteins (DEPs) in at least one of four predefined comparisons using a standardized procedure to extract and align data. Network analysis of functional protein associations was made with StringApp in Cytoscape. A protocol for this review was registered in the PROSPERO database (ref:CRD42022363226). <b><i>Results:</i></b> We identified and assessed 772 studies published between December 2, 1996, and April 28, 2023, among which 30 studies met the inclusion and data availability criteria for analysis that together reported a sum of 5,314 DEPs. The majority of consistently reported upregulated and downregulated proteins were found in lesional versus non-lesional skin (<i>n</i> = 313), followed by lesional versus healthy skin (<i>n</i> = 185), blood from patients with psoriasis versus blood from healthy individuals (<i>n</i> = 140), and non-lesional versus healthy skin (<i>n</i> = 1). Network analysis of upregulated proteins revealed different functional clusters with interleukin (IL)-6, IL-8, IL-17A, C-C motif chemokine (CCL) 20, signal transducer and activator of transcription (STAT) 3, and interferon (IFN)-γ along with less well-studied proteins playing central roles. Some of the reported changes are associated with anti-inflammatory effects. Additionally, the proteomic dysregulation also included antimicrobial peptides, alarmins, angiogenic factors, and proteins related to protein synthesis. <b><i>Conclusion:</i></b> Our findings generally support current understandings of the pathological mechanisms in psoriasis. Importantly, some consistent findings have not been discussed before and deserve attention in future research.

Biological agent exerts therapeutic effects by reversing abnormalities in amino acid metabolic pathways in psoriasis

“…To further strengthen the validity of our results, we conducted a comparison between the aberrant genes we identified and the proteomics studies specifically related to psoriasis. 23 This comparison revealed 19 genes that exhibited significant alterations in protein levels in psoriatic patients, which aligns with our initial research hypotheses. Significantly, five of these genes, namely ALDH2, GOT2, GPT, BCAT2 and PSAT1, were found to be in perfect agreement with our previously identified top 10 genes (Figure 6B).…”

“…These hub genes were determined to be MAT2A, GLUD1, BCAT1, BCAT2, GOT2, GPT2, GPT, PSAT1, ALDH1B1 and ALDH2 (Figure 6B). To further strengthen the validity of our results, we conducted a comparison between the aberrant genes we identified and the proteomics studies specifically related to psoriasis 23 . This comparison revealed 19 genes that exhibited significant alterations in protein levels in psoriatic patients, which aligns with our initial research hypotheses.…”

“…L stood for lesion, NL represented non‐lesion and HC denoted healthy control. The data of figure C were obtained from Kromann, B/2023 23 …”