Current knowledge on autoantigens and autoantibodies in psoriasis

Abstract

Psoriasis is a chronic inflammatory disease of the skin, with clinically characteristic erythematous and thick scaling plaques. 1 It is now well acknowledged that in addition to psoriatic arthritis (PsA), other comorbidities such as metabolic syndrome, cardiovascular diseases, gastrointestinal diseases, psychosocial disorders, infections and malignancies may accompany psoriasis. 2 They appear to result from environmental (e.g., infection or skin trauma) and genetic factors as well as enhanced levels of various inflammatory mediators, in particular circulating lymphocytes and other peripheral blood mononuclear cells, transcription factors and cytokines like tumour necrosis factor (TNF), interleukin (IL)-12/IL-23 and IL-17. 3-5 Multiple susceptibility loci associated with innate and adaptive components of the immune system together with skin resident cell types are involved in the complex inflammatory network that drives psoriatic disease. 6 The most predominant susceptibility allele for psoriasis, the human leucocyte antigen (HLA) susceptibility locus HLA-C*06:02, is strongly associated with early onset and more severe disease. 1 To date, it has been agreed that psoriasis is

Skin Barrier Dysregulation in Psoriasis

“…Keratinocytes trigger psoriatic inflammation by producing autoantigens—including cathelicidin (LL-37), a disintegrin and metalloprotease domain containing thrombospondin type 1 motif-like 5, the neolipids associated with phospholipase A2 group IVD (PLA2G4D), and Keratin 17 [ 66 ]. Keratinocytes, additionally, facilitate DC autoantigen recognition by producing polyamines which prevent degradation of autoantigenic RNA [ 67 ].…”

Key Signaling Pathways in Psoriasis: Recent Insights from Antipsoriatic Therapeutics

“…The most studied autoantigen is cathelicidin antimicrobial peptide, also known as LL-37, which is produced by immune cells and keratinocytes in response to skin injury ( Figure 1 ). 11 , 12 LL-37 forms complexes with self-DNA or RNA that activates plasmacytoid DCs (pDCs) through Toll-like receptor-9 (TLR-9) and TLR-7, respectively. 13 , 14 Subsequently, the pDCs produce interferon (IFN)-α that activates conventional DCs (cDCs).…”

The Role of IL-36 in the Pathophysiological Processes of Autoimmune Diseases

“…( Mahil et al, 2017 ) The findings demonstrated the enhanced expression of PLA2G4D in psoriatic epidermis , which was comparable to normal skin and eczematous lesions. ( Ten Bergen et al, 2020 ) Besides, mast cells, as one of the immune cells, were the main cell source of PLA2G4D, so it was not difficult to speculate the relationship between PLA2G4D and immune diseases. IL-36 could upregulate phospholipase PLA2G4D, which generated lipid antigen-presenting CD1A reactive T lymphocytes.…”

“…IL-36 could upregulate phospholipase PLA2G4D, which generated lipid antigen-presenting CD1A reactive T lymphocytes. Stimulation of this cell led to the production of IL-17 and IL-22 ( Ten Bergen et al, 2020 ).…”