Brodalumab-an IL-17RA monoclonal antibody for psoriasis and psoriatic arthritis

Bauer, Erin; Lucier, Jessica; Fürst, Daniel E.

doi:10.1517/14712598.2015.1045410

Cited by 21 publications

(17 citation statements)

References 36 publications

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“…Ixekizumab is a humanized IgG4 MAB that neutralizes IL-17A [42]. Brodalumab is a fully human, IgG2 anti-Il-17RA MAB, which binds IL-17RA with high affinity; this activity impedes the interaction between the receptor and IL-17A/E/F, which thereby disrupts the IL-17 pathway [43] (Appendix).…”

Section: Resultsmentioning

confidence: 99%

Psoriasis: Keratinocytes or Immune Cells – Which Is the Trigger?

2018

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Background: Psoriasis is a common, chronic inflammatory skin disorder, which can significantly impact quality of life. Despite major breakthroughs in our understanding of the pathogenesis of psoriasis, the chronological order of the underlying mechanisms leading to the development of psoriatic plaques remains to be completely understood. Summary: Although psoriasis is classically perceived as a T-cell disease, it is now well recognized that T lymphocytes do not function in exclusivity. This theory is supported by evidence from transgenic murine models that develop marked psoriasiform disease. In addition, immune cells and cytokines regulate both early and late events involved in the pathogenesis of psoriasis. Key Messages: Psoriasis is a complex disease – a dynamic interplay between immune cells, keratinocytes, and various other skin-resident cells, such as endothelial and immune cells. The contribution of each cell type is crucial in the initiation and maintenance phases of psoriatic alterations.

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Section: Resultsmentioning

confidence: 99%

Psoriasis: Keratinocytes or Immune Cells – Which Is the Trigger?

2018

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“…The IL-17RA subunit is required for the signaling of several IL-17 isoforms (IL-17A, IL-17C, IL-17F, IL-17E) (Gaffen et al, 2014) and has recently proven to be a valid target to treat psoriasis (Bauer et al, 2015;Papp et al, 2014). By immunohistochemistry, we compared the expression of IL-17 isoforms signaling via IL-17RA in lesional (PP) and non-lesional (PN) skin from psoriatic patients as well as normal human skin (NN).…”

Section: Keratinocytes Produce High Levels Of Il-17e In Psoriatic Lesmentioning

confidence: 99%

Keratinocyte-Derived IL-17E Contributes to Inflammation in Psoriasis

Senra

Stalder

Martínez

et al. 2016

Journal of Investigative Dermatology

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Psoriasis is a chronic inflammatory skin disorder effectively treated by blocking IL-17RA, a receptor chain used by several IL-17 family members, including IL-17E. Although IL-17A is critically involved in the pathogenesis of psoriasis, the contribution of IL-17E remains unknown. Here we show that IL-17E(+) cells are more abundant than IL-17A(+) cells in lesional psoriatic skin. IL-17E synthesis is increased in keratinocytes within psoriatic plaques, and macrophages having a mixed M1/M2 phenotype represent an important proportion of the IL-17E(+) cells infiltrating the dermis. Mechanistically, macrophages do not synthetize but rather take up IL-17E via receptor-mediated clathrin-dependent endocytosis. Furthermore, monocyte-derived macrophages in vitro polarized in M2, but not M1, express the IL-17E receptor and respond to IL-17E by preferentially producing inflammatory cytokines and chemokines involved in neutrophil recruitment. Remarkably, IL-17E expression in lesional psoriatic skin correlates with the number of neutrophils while being inversely proportional to the number of infiltrating T cells. These data provide strong evidence for a proinflammatory role of keratinocyte-derived IL-17E in psoriasis, possibly via macrophage activation.

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“…Several human monoclonal antibodies directed against IL-17 are in development, including brodalumab (AMG 827), ixekizumab (LY2439821), and secukinumab (Cosentyx; Novartis, Basel, Switzerland). Clinical development of these humanized monoclonal antibodies has focused on psoriasis, where they have been shown to be effective [132,133]. The contribution of IL-6 in MG is suggested by its activity as a promoter of B-cell differentiation and proliferation and in the induction of B-cell maturation into antibody-producing plasma cells [134].…”

Section: Cytokine Cytokine Receptors and Growth Factorsmentioning

confidence: 99%

Current Treatment, Emerging Translational Therapies, and New Therapeutic Targets for Autoimmune Myasthenia Gravis

2016

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Myasthenia gravis (MG) is an autoimmune disease associated with the production of autoantibodies against 1) the skeletal muscle acetylcholine receptor; 2) muscle-specific kinase, a receptor tyrosine kinase critical for the maintenance of neuromuscular synapses; 3) low-density lipoprotein receptor-related protein 4, an important molecular binding partner for muscle-specific kinase; and 4) other muscle endplate proteins. In addition to the profile of autoantibodies, MG may be classified according the location of the affected muscles (ocular vs generalized), the age of symptom onset, and the nature of thymic pathology. Immunopathologic events leading to the production of autoantibodies differ in the various disease subtypes. Advances in our knowledge of the immunopathogenesis of the subtypes of MG will allow for directed utilization of the ever-growing repertoire of therapeutic agents that target distinct nodes in the immune pathway relevant to the initiation and maintenance of autoimmune disease. In this review, we examine the pathogenesis of MG subtypes, current treatment options, and emerging new treatments and therapeutic targets.

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Brodalumab-an IL-17RA monoclonal antibody for psoriasis and psoriatic arthritis

Cited by 21 publications

References 36 publications

Psoriasis: Keratinocytes or Immune Cells – Which Is the Trigger?

Psoriasis: Keratinocytes or Immune Cells – Which Is the Trigger?

Keratinocyte-Derived IL-17E Contributes to Inflammation in Psoriasis

Current Treatment, Emerging Translational Therapies, and New Therapeutic Targets for Autoimmune Myasthenia Gravis

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