Psoriasis is present in all racial groups but in varying frequencies
Psoriasis is present in all racial groups but in varying frequencies and severity. dendritic cells in total psoriatic skin area were exponentially increased. Negative immune regulators such as CD69 and FAS were decreased in both Western plaque psoriasis and psoriasis with accompanying arthritis or obesity and their expression was correlated with psoriasis severity index. Based on the disease subtype comparisons we propose that dysregulation of T cell expansion enabled by downregulation of immune negative regulators is the main mechanism for development of large plaque psoriasis subtypes. < 0.01 and FDR < 0.01; Supplementary Figure S4 online). Histological findings in Asian small and intermediate psoriasis also revealed hallmarks of histological findings in Western large psoriasis. In the psoriatic lesional skin of both Asian small and intermediate psoriasis the epidermis revealed hyperplasia with focal parakeratosis (Supplementary Figure S3 online immunohistochemical images). Key cellular subsets of psoriasis immunopathogenesis CD3+ T cells and CD11c+ myeloid dendritic cells accumulated in both subtypes. Numbers of CD3+ T cells and CD11c+ dendritic cells in Asian small Sulindac (Clinoril) psoriasis were not different from Western large psoriasis in slide sections of lesional skin (Supplementary Figure S5 online). Number of CD3+ T cells in Asian intermediate psoriasis was also not different from Western large psoriasis while CD11c+ dendritic cells were more abundant in Sulindac (Clinoril) Asian intermediate psoriasis compared to Western large psoriasis. Taken together Asian small and intermediate psoriasis phenotypes were validated as psoriasis variants sharing a common psoriasis transcriptome and histologic findings with Western large psoriasis (psoriasis vulgaris). Models of disease progression emerge from subtype comparisons We next explored models of disease progression by correlating two different phases of disease progression: vertical growth Sulindac (Clinoril) (epidermal hyperplasia) measured by epidermal thickness of lesional skin and radial expansion (the extension of overall psoriasis area and severity) measured by PASI (Figure 2). Since Asian small psoriasis was limited in both epidermal thickness and PASI we considered it as a model of the initial stage of disease progression. Figure 2 Exploratory models of disease progression To explore mechanisms of vertical growth we compared Asian small and intermediate psoriasis since epidermal thickness was significantly different between the two subtypes without a difference in PASI (Figure 2a). In this model CD3+ T cell and CD11c+ dendritic cell infiltrates within the epidermis and dermal papillary area were significantly different (Supplementary Figure S6 online). In addition CD3+ T cells and CD11c+ Mouse monoclonal to CD38.TB2 reacts with CD38 antigen, a 45 kDa integral membrane glycoprotein expressed on all pre-B cells, plasma cells, thymocytes, activated T cells, NK cells, monocyte/macrophages and dentritic cells. CD38 antigen is expressed 90% of CD34+ cells, but not on pluripotent stem cells. Coexpression of CD38 + and CD34+ indicates lineage commitment of those cells. CD38 antigen acts as an ectoenzyme capable of catalysing multipe reactions and play role on regulator of cell activation and proleferation depending on cellular enviroment. dendritic cells within the epidermis and dermal papillary area were linearly correlated with the epidermal thickness (Figure 2b and 2d; Supplementary Table S2 online). To explore mechanisms of radial expansion we compared Asian intermediate and Western large psoriasis since PASI was significantly different between the two subtypes without a difference in epidermal thickness (Figure 2a). In this model the accumulated T cell and dendritic cell numbers in total psoriasis body surface area of Western large psoriasis (CD3+ T cells: 6.24×109 ± Sulindac (Clinoril) 4.68×109 CD11c+ dendritic cells: 5.13×109 ± 4.74×109) were exponentially higher than the numbers for Asian intermediate psoriasis (CD3+ T cells: 1.18×109 ± 9.76×108 CD11c+ dendritic cells: 1.45×109 ± 1.43×109) (Supplementary Figure S5 online). In addition CD3+ T cells and CD11c+ dendritic cells in total psoriasis body surface area were highly correlated to PASI (Figure 2c and 2d; Supplementary Table S2 online). Genomic exploration of disease progression models To explore molecular correlates of disease progression we simultaneously measured expression levels of 35 genes in both lesional and non-lesional skin of Asian small (N=16) Asian intermediate (N=21) and Western large (N=20) psoriasis by RT-PCR (Figure 3 and Supplementary Sulindac (Clinoril) Figure S7 online). In the model of the initial stage of disease progression IL-17A and IL-17-regulated pro-inflammatory cytokines (IL-1B and IL-8) were.