Variable roles of interleukin-17F in different cancers

Background Interleukin (IL)-17 family is a group of six cytokines that plays a central role in inflammatory processes and participates in cancer progression. Interleukin-17A has been shown to have mainly a protumorigenic role, but the other members of the IL-17 family, including IL-17F, have received less attention. Methods We applied systematic review guidelines to study the role of IL-17F, protein and mRNA expression, polymorphisms, and functions, in cancer. We carried out a systematic search in PubMed, Ovid Medline, Scopus, and Cochrane libraries, yielding 79 articles that met the inclusion criteria. Results The findings indicated that IL-17F has both anti- and protumorigenic roles, which depend on cancer type and the molecular form and location of IL-17F. As an example, the presence of IL-17F protein in tumor tissue and patient serum has a protective role in oral and pancreatic cancers, whereas it is protumorigenic in prostate and bladder cancers. These effects are proposed to be based on multiple mechanisms, such as inhibition of angiogenesis, vasculogenic mimicry and cancer cell proliferation, migration and invasion, and aggravating the inflammatory process. No solid evidence emerged for the correlation between IL-17F polymorphisms and cancer incidence or patients’ prognosis. Conclusion IL-17F is a multifaceted cytokine. There is a clear demand for more well-designed studies of IL-17F to elucidate its molecular mechanisms in different types of cancer. The studies presented in this article examined a variety of different designs, study populations and primary/secondary outcomes, which unfortunately reduces the value of direct interstudy comparisons.

Elevated X-Box Binding Protein1 Splicing and Interleukin-17A Expression Are Associated With Active Generalized Vitiligo in Gujarat Population

Vitiligo is an autoimmune skin disorder defined by the destruction of functional epidermal melanocytes. It is a multifactorial and polygenic disorder caused due to oxidative stress, endoplasmic reticulum (ER) stress, and autoimmunity, among other factors. In the present study, we aimed to investigate the association of X-box Binding Protein 1 (XBP1) and Interleukin-17A (IL-17A) polymorphisms and monitor their systemic as well as skin expression levels in vitiligo patients from Gujarat population in India. XBP1 rs2269577 G/C, IL17A rs2275913 G/A and IL17A rs8193036 C/T polymorphisms were genotyped by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method in 312 controls and 276 vitiligo patients. Transcript levels of spliced (sXBP1), unspliced XBP1 (uXBP1) and IL17A from peripheral blood mononuclear cells (PBMCs) as well as spliced and unspliced XBP1 from skin samples were analyzed by qPCR. IL-17A protein levels in suction-induced blister fluid (SBF) from the skin of study subjects were estimated by ELISA. The results revealed that genotype (p=0.010) and allele (p=0.014) frequencies of XBP1 rs2269577 G/C polymorphism were significantly different, however, no significant difference was observed in frequencies of IL17A rs2275913 G/A and IL17A rs8193036 C/T polymorphisms in control and patient population. Gene expression analysis revealed that sXBP1 and IL17A levels were significantly higher in PBMCs of generalized (p=0.030 and p=0.039, respectively) and active (p=0.024 and p=0.017, respectively) vitiligo patients. Moreover, we observed a significantly elevated sXBP1 expression (p=0.037) as well as IL-17A protein levels (p=0.009) in perilesional skin of vitiligo patients as compared to controls. Overall, these findings suggest XBP1 and IL17A play an important role in vitiligo and further substantiate the involvement of ER stress in exacerbating immune-mediated vitiligo pathogenesis.

Subgingival Microbiota and Cytokines Profile Changes in Patients with Periodontitis: A Pilot Study Comparing Healthy and Diseased Sites in the Same Oral Cavities

Periodontitis is a common condition characterized by an exacerbated pro-inflammatory response, which leads to tissue destruction and, ultimately, alveolar bone loss. In this pilot study, we assess the microbiota composition and cytokine profile changes in patients with stage III/IV, grade B/C periodontitis, specifically by comparing healthy and diseased sites in the same oral cavity. Overall, we found that microbiota architecture was significantly disrupted between diseased and healthy sites, and that the clustering was driven, in part, by the increased relative abundances of Synergistetes in diseased sites, as well as the increased abundances of Firmicutes in healthy sites. We also observed that diseased sites were enriched in Synergistetes, TM7, SR1, Spirochaetes, Bacteroidetes and Fusobacteria, and depleted in Firmicutes, Proteobacteria, Tenericutes and Actinobacteria compared to healthy sites. We found that Interleukin-1b, Interleukin-4, Interleukin-10, and Interleukin-17A were significantly overexpressed in diseased sites, whereas Interleukin-6 and TNF-alpha do not differ significantly between healthy and diseased sites. Here, we observed concomitant changes in the subgingival plaque microbiota and cytokines profile, suggesting that this combined alteration could contribute to the pathobiology of periodontitis.

Einsatz von Secukinumab bei Patienten mit Psoriasis und Psoriasis-Arthritis – Ergebnisse einer nichtinterventionellen Studie unter Praxisbedingungen (SERENA-Studie)

<b>Introduction:</b> Secukinumab, a fully human monoclonal antibody that directly inhibits interleukin-17A, has demonstrated robust efficacy in the treatment of moderate to severe psoriasis (PsO), psoriatic arthritis (PsA) and ankylosing spondylitis (AS), with a rapid onset of action, sustained long-term clinical responses and a consistently favourable safety profile across phase 3 trials. Here, we report the clinical data at enrolment from SERENA, designed to investigate the real-world use of secukinumab across all three indications. <b>Methods:</b> SERENA is an ongoing, longitudinal, observational study conducted at 438 sites across Europe in patients with moderate to severe plaque PsO, active PsA or active AS. Patients should have received at least 16 weeks of secukinumab treatment before enrolment in the study. <b>Results:</b> Overall 2800 patients were included in the safety set; patients with PsA (N = 541) were older than patients with PsO (N = 1799) and patients with AS (N = 460); patients with PsO had a higher mean body weight than patients with PsA and patients with AS; and patients with PsO and patients with AS were predominantly male. Time since diagnosis was longer in patients with PsO compared with patients with PsA and patients with AS, and about 40% of patients were either current or former smokers. The proportion of obese patients (body mass index ≥ 30 kg/m²) was similar across indications. Patients were treated with secukinumab for a mean duration of 1 year prior to enrolment (range 0.89–1.04). The percentages of patients with prior biologics exposure were 31.5% PsO, 59.7% PsA and 55% AS. The percentages of patients prescribed secukinumab monotherapy were 75% (n = 1349) in PsO, 48.2% (n = 261) in PsA and 48.9% (n = 225) in AS groups. <b>Conclusion:</b> Baseline demographics of the study population are consistent with existing literature. This large observational study across all secukinumab indications will provide valuable information on the long-term effectiveness and safety of secukinumab in the real-world setting.

Increased serum interleukin-17A levels correlate with disease severity and poor prognostic factors in patients with alopecia areata

Background: Alopecia areata (AA) is a tissue-specific autoimmune disease characterized by non-scarring and rapid onset of hair loss. Interleukin (IL)-17A is mainly produced by T helper 17 (Th17) cells and may play a crucial role in the pathogenesis of various autoimmune diseases including AA.Objectives: We conducted this research to measure serum level of IL-17A in patients with AA and investigated its relationship with the clinical manifestations in patients with AA.Methods: We assessed 36 patients with AA and 20 healthy control subjects. Demographic information and clinical characteristics were determined by physical examination and via the review of medical history. Serum IL-17A was measured by using enzyme-linked immunosorbent assay.Results: Serum IL-17A concentration was significantly higher in patients with AA than in the control group (P=0.004). The AA patients with severe presentation, personal atopy, nail abnormalities, or active phase had significantly higher serum IL-17A levels compared to others without these signs.Conclusion: Increased serum IL-17A levels in patients with AA correlate with severity and indicate an active disease state. These findings suggest that IL-17A may play an important role in determining the pathogenesis of AA and may serve as a valuable clinical biomarker of this disease.