Ultra-Sensitive Measurement of IL-17A and IL-17F in Psoriasis Patient Serum and Skin

Soderstrom, Catherine; Berstein, Gabriel; Zhang, Weidong; Valdez, Hernán; Fitz, Lori; Kuhn, Max; Fraser, Stephanie

doi:10.1208/s12248-017-0094-4

Cited by 39 publications

(33 citation statements)

References 13 publications

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“…In this study, we used a highly sensitive measurement for serum IL‐17 in a large cohort of patients with psoriasis treated with tofacitinib or etanercept. In PASI75 responders to tofacitinib and etanercept, serum IL‐17A concentrations at weeks 4 and 12 decreased to a much larger extent than in nonresponders, and reached low levels that were within the range previously reported in normal subjects (0.057–0.269 pg/mL) . Although tofacitinib and etanercept do not block IL‐17 signalling directly, the association between decreases in IL‐17A and clinical response suggests that normalization of circulating IL‐17A is required for psoriasis remission regardless of the therapeutic agent.…”

Section: Discussionmentioning

confidence: 78%

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Association between serum interleukin-17A and clinical response to tofacitinib and etanercept in moderate to severe psoriasis

et al. 2018

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SummaryBackground. Psoriasis is a systemic inflammatory disease with a pathophysiology involving interleukin (IL)-17. Tofacitinib is an oral Janus kinase inhibitor. Etanercept is a tumour necrosis factor-a inhibitor used in the treatment of psoriasis. Neither agent inhibits IL-17 directly. Aim. To evaluate correlations between circulating IL-17A and clinical efficacy in patients with psoriasis treated with tofacitinib or etanercept. Methods. Serum concentrations of IL-17A homodimer and IL-17A/F heterodimer were determined by immunoassays at weeks 0, 4 and 12 in patients with moderate to severe psoriasis treated with placebo (n = 60), tofacitinib 5 mg twice daily (n = 184), tofacitinib 10 mg twice daily (n = 190), or etanercept 50 mg subcutaneously twice weekly (n = 190). Disease severity was assessed using the Psoriasis Area and Severity Index (PASI) and clinical response was defined as patients achieving ≥ 75% improvement from baseline PASI (PASI75). Results. Serum levels of IL-17A homodimer at week 0 showed moderate correlation with PASI, with a Spearman correlation coefficient of 0.43. Furthermore, serum levels of IL-17A homodimer showed a clear correlation with clinical response, with a decrease of 57.1% in patients achieving PASI75 at week 12, but only 15.9% decrease in nonresponders. PASI75 responders had lower median concentrations of IL-17A (range across treatments: 0.24-0.27 pg/mL) at week 12 vs. nonresponders (0.37-0.62 pg/mL), regardless of the treatment. Serum IL-17A/F heterodimer showed similar decreases at week 12 in responders and nonresponders. Conclusions. Baseline serum IL-17A correlates moderately with psoriasis severity. Reduction in circulating IL-17A is required for disease remission regardless of therapeutic agent.

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Section: Discussionmentioning

confidence: 78%

“…Serum concentrations of IL‐17A/A homodimer (IL‐17A) and IL‐17A/F heterodimer (IL‐17A/F) were measured by validated methods, using commercial kits (Singulex Inc., Alameda, CA, USA) and immunoassays were performed (Erenna ® Immunoassay System; Singulex Inc.).…”

Section: Methodsmentioning

confidence: 99%

Association between serum interleukin-17A and clinical response to tofacitinib and etanercept in moderate to severe psoriasis

et al. 2018

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“…To understand the mechanisms for the induction of MMPs in skin, IL-17-related inflammatory models are important. Indeed, the significance of IL-17 was reported in autoimmune diseases such as psoriasis [15], bullous pemphigoid (BP) [16,17], and alopecia areata [18]. Among them, Riani et al [16] reported that IL-17 increased CXCL10 in inflammatory cells, leading to an augmented secretion of MMP9 from neutrophils and monocytes in BP patients.…”

Section: Discussionmentioning

confidence: 99%

IL-23 Expression in Stewart-Treves Syndrome: Two Case Reports and Immunohistochemical Investigation

et al. 2020

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Stewart-Treves syndrome (STS) is a rare cutaneous lymphangiosarcoma developing from chronic lymph edema as a consequence of radical mastectomy or surgical invasion of the groin for the treatment of cervical or penile cancer. Previous reports suggested possible mechanisms in the development of lymphangiosarcoma that correlate with the immunological background of STS patients. In this report, we described two cases of STS developing in patients who underwent radical dissection for cervical cancer, we employed immunohistochemical staining of IL-23 and IL-17. Case ReportCase 1 A 79-year-old Japanese woman visited our outpatient clinic with a 1-month history of a red, easy to bleed, nodule on the right femur. She had undergone resection of a cervical cancer 24 years before and developed prominent lymph edema in the lower extremities. During her initial visit, physical examination revealed a dark-red nodule with extended purpura on the right femur together with prominent lymph edema (Fig. 1a). Histologically, these were irregularly anastomosing vascular channels lined by single layers of enlarged, atypical endothelial cells that existed between the collagen bundles (Fig. 1b). Immunohistochemical staining revealed that these atypical endothelial cells were positive for vimentin, CD31, CD34, D2-40, and Factor VIII. The Ki67 score was 90%. Moreover, a substantial number of IL-23-producing cells (Fig. 1c) as well as IL-17-producing cells (Fig. 1d) were detected at the edge of the tumor mass. Positron emission tomography scans showed no evidence of metastases. From the

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“…erefore, we expect that IL-17A exerted its effect at local inflammatory sites of psoriatic skin rather than the circulation. Another possibility is that Mo-MDSCs downregulate IL-17A levels in circulation [31]. e transcription factor ROR-c plays a critical role in the expression of proinflammatory cytokine IL-17 in patients with psoriasis [32] and is, therefore, an attractive target for the treatment of psoriasis [33].…”

Section: Discussionmentioning

confidence: 99%

Circulating CD14⁺HLA‐DR^−/low Myeloid‐Derived Suppressor Cells as Potential Biomarkers for the Identification of Psoriasis TCM Blood‐Heat Syndrome and Blood‐Stasis Syndrome

Sun

Wei

Zeng

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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Psoriasis is a chronic autoimmune disease. Identification of the biomarkers responsible for Traditional Chinese Medicine (TCM) syndromes of psoriasis can help researchers recognize the different aspects of psoriasis and find novel therapeutic targets for the treatment of psoriasis. The current study investigated the levels of circulating Mo-MDSCs and Mo-MDSC-associated immune factors in the peripheral blood of psoriasis patients with different TCM syndromes. We found that the frequency of Mo-MDSCs (CD14+HLA-DR−/low cells) among CD14+ cells from plaque psoriasis patients with blood-stasis (BS) syndrome was significantly increased when compared with healthy controls p<0.001 and blood-heat (BH) syndrome group p<0.001, respectively. However, serum IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, IFN-γ, iNOS, Arg-1, and NO concentration showed no statistically significant difference between healthy controls and psoriasis patients as well as no significant difference between the BH and BS syndrome groups. Compared with healthy controls, the mRNA expression of Arg-1, TNF-α, ROR-γ, and PD-L1 was increased, while the mRNA expression of PD-1 and IL-10 was decreased in PBMCs from psoriasis patients. Moreover, the mRNA expression of TNF-α and FOXP3 in PBMCs showed a pronounced statistical difference between the psoriatic BH syndrome group and the BS syndrome group. Therefore, we provide evidence that the percentage of CD14+HLA-DR−/low MDSC/ CD14+ cells and TNF-α and Foxp3 mRNA expression levels in PBMCs are potential biomarkers for distinguishing TCM BH syndrome and BS syndrome.

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Ultra-Sensitive Measurement of IL-17A and IL-17F in Psoriasis Patient Serum and Skin

Cited by 39 publications

References 13 publications

Association between serum interleukin-17A and clinical response to tofacitinib and etanercept in moderate to severe psoriasis

Association between serum interleukin-17A and clinical response to tofacitinib and etanercept in moderate to severe psoriasis

IL-23 Expression in Stewart-Treves Syndrome: Two Case Reports and Immunohistochemical Investigation

Circulating CD14⁺HLA‐DR^−/low Myeloid‐Derived Suppressor Cells as Potential Biomarkers for the Identification of Psoriasis TCM Blood‐Heat Syndrome and Blood‐Stasis Syndrome

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Ultra-Sensitive Measurement of IL-17A and IL-17F in Psoriasis Patient Serum and Skin

Cited by 39 publications

References 13 publications

Association between serum interleukin-17A and clinical response to tofacitinib and etanercept in moderate to severe psoriasis

Association between serum interleukin-17A and clinical response to tofacitinib and etanercept in moderate to severe psoriasis

IL-23 Expression in Stewart-Treves Syndrome: Two Case Reports and Immunohistochemical Investigation

Circulating CD14+HLA‐DR−/low Myeloid‐Derived Suppressor Cells as Potential Biomarkers for the Identification of Psoriasis TCM Blood‐Heat Syndrome and Blood‐Stasis Syndrome

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Product

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Circulating CD14⁺HLA‐DR^−/low Myeloid‐Derived Suppressor Cells as Potential Biomarkers for the Identification of Psoriasis TCM Blood‐Heat Syndrome and Blood‐Stasis Syndrome