Assessment and Clinical Relevance of Serum IL-19 Levels in Psoriasis and Atopic Dermatitis Using a Sensitive and Specific Novel Immunoassay

Abstract

Because development of reliable biomarkers in psoriasis and atopic dermatitis has lagged behind therapeutic progress, we created a blood-based test to fill the void in objective methods available for dermatological assessments. Our novel interleukin-19 (IL-19) immunoassay was initially tested to determine concentrations of IL-19 serum levels, then correlated with the psoriasis activity and severity index (PASI) in psoriasis, and the eczema area and severity index (EASI) in atopic dermatitis. Not only was IL-19 increased in psoriasis and correlated to PASI, but ixekizumab administration led to rapid, sustained IL-19 decreases to normal levels, with decreases at 2-weeks correlating with PASI improvement at 16-weeks. IL-19 increased upon ixekizumab withdraw, prior to relapse, and decreased following re-treatment. In baricitinib- and etanercept-treated psoriasis patients, IL-19 decreases also correlated with improvement. Many patients with limited skin disease, including genital psoriasis and psoriatic arthritis patients, also had increased IL-19, which was reduced to normal levels upon ixekizumab treatment, correlating with PASI improvement. We also measured IL-19 in baricitinib-treated atopic dermatitis patients. In atopic dermatitis, IL-19 was significantly elevated, correlated with EASI scores, and decreased with skin improvement. Therefore, measurement of serum IL-19 provides clinicians with an objective disease-activity assessment tool for psoriasis and atopic dermatitis patients.

Characterization of the cytokine storm reflects hyperinflammatory endothelial dysfunction in COVID-19

“…Proteomic profiling of peripheral blood samples from patients with COVID- 19 We used multiplex methodology from Olink Proteomics to assess 184 analytes, spanning a broad range of cytokines and chemokines involved in inflammation (inflammation panel 1 [INF I]) and cardiovascular-linked processes (CVD II), and, on the basis of inflammatory responses described in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected lung epithelium, we also measured IL-19 levels using a highly sensitive and specific assay as previously described. [2][3][4] The descriptions for the short form of the individual biomarkers in the Olink panel have been described earlier. 3 Analysis of the differential protein regulation patterns within severity classes of COVID-19 cases compared with healthy control (HC) revealed strong dysregulation of IFN-g, IL-6, IL-10, monocyte chemoattractant protein (MCP)-3, CXCL9, CXCL10, We observed a 2-fold increase in IL-19 levels and, along with the aforementioned changes in IL-10, MCP-1, -2, and -3, this is consistent with the important role for inflammatory monocytes/macrophages in the immunopathogenesis of patients infected with COVID-19.…”

Mouse models of atopic dermatitis: a critical reappraisal

“…The upregulation of Th2‐associated cytokines enhances IgE production (Figure 1F), resulting in the enhanced deposition of IgE on FcεR expressing cells, such as mast‐cells and Langerhans cells, and aggravates both skin inflammation and the skin barrier defect in AD 9,21 . It is not only IL‐17 (Figure 1G) that has been described in AD, but also Th17, Th22 and Th2/17 intermediate cells 39‐41 . Moreover, innate lymphoid cells (ILCs) are capable of producing AD‐associated type 2 cytokines such as IL‐4 and IL‐13.…”

“…9,21 It is not only IL-17 ( Figure 1G) that has been described in AD, but also Th17, Th22 and Th2/17 intermediate cells. [39][40][41] Moreover, innate lymphoid cells (ILCs) are capable of producing AD-associated type 2 cytokines such as IL-4 and IL-13. Yet, "AD" mouse models typically do not present evidence as to whether ILCs in humans and mice share the same function with respect to IL-4-and IL-13-induced immunomodulation and pruritus.…”

The role of interleukin-24 in atopic dermatitis

“…Chong et al [37] found that IL-17A induced IL-24 production in Th17 cells. Considering that IL-17A signals through the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway [38] and two potential NF-κB binding sites are present in the IL-24 gene, the researchers proposed that the binding of IL-17A to its receptor activates NF-κB signaling, leading to the transcription of IL-24 in Th17 cells [37]. IL-22 induced the production of IL-24 in normal human keratinocytes [15,39,40].…”