Anti-IL17A monoclonal antibody, clone 30C5.H20.G6

Arsenic and polycyclic aromatic hydrocarbons (PAH) are environmental pollutants to which people around the world are exposed through water, food and air. In mouse and in vitro studies of human cells, both of these chemicals have been shown to modulate the immune system. In some experimental studies, a synergistic disruption of immune function was observed by a combined exposure to arsenic and PAH. However, a joint effect of arsenic and PAH on immune function has not been studied in humans. We have conducted an epidemiological investigation to examine effects of chronic arsenic and PAH exposures on immune function. We assessed T-cell proliferation (TCP) and cytokine production of anti-CD3/anti-CD28 stimulated lymphocytes in human peripheral blood mononuclear cells (HPBMC) among 197 healthy men enrolled to the Health Effects of Arsenic Longitudinal (HEALS) cohort in Bangladesh. By design, approximately half were active smokers and the rest were never smokers. Our analyses demonstrated that IL-1b, IL-2, IL-4 and IL-6 were significantly stimulated as a function of urinary arsenic levels in models adjusted for age, body mass index (BMI), smoking status and PAH-DNA adducts. After correcting for false detection rate (FDR), only IL-1b remained statistically significant. We found a U-shaped dose response relationship between urinary arsenic and IL-1b. On the other hand, PAH-DNA adducts were associated with an inhibition of TCP and appeared as an inverted U-shape curve. Dose response curves were non-monotonic for PAH-DNA adduct exposures and suggested that cytokine secretion of IFNg, IL-1b, IL-2, IL-10 and IL17A followed a complex pattern. In the majority of donors, there was a trend towards a decrease in cytokine associated with PAH-DNA adducts. We did not observe any interaction between urinary arsenic and PAH-DNA adducts on immune parameters. Our results indicate that long-term exposures to arsenic and PAH have independent, non-monotonic associations with TCP and cytokine production.

Introduction: Psoriasis is a common, systemic, inflammatory disease with prominent skin and joint manifestations. Interleukin 17A (IL-17A) has been identified as a key effector cytokine that mediates immunopathogenesis of psoriasis. Ixekizumab, a humanized monoclonal antibody that targets IL-17A, has been found in clinical trials to dramatically reduce signs and symptoms of moderate-to-severe plaque psoriasis.Areas covered: The following areas are discussed: the basic structure and function of IL-17A, its role in the pathogenesis of psoriasis, the safety and efficacy of ixekizumab in clinical trials reported to date, and the possible impact of ixekizumab on the future therapeutic market for psoriasis.Expert opinion: A large proportion of patients with psoriasis achieve clear or near clear skin during treatment with ixekizumab in a rapid and sustained manner. This supports the idea that IL-17A plays a central role in psoriasis immunopathogenesis. While ixekizumab has been shown to be safe in trials up to 60 weeks, long-term safety data are not yet available. Because its efficacy is higher than all previously approved drugs for psoriasis thus far, approval and use of ixekizumab may lead to a treatment paradigm change for psoriasis, where clear or near clear skin becomes an acceptable and achievable treatment goal.