Targeted immunotherapy, especially for cytokines, has acted as a important role in the immunotherapy of psoriasis:
TNF antagonists have proven to be highly effective for the treatment of psoriasis. The three agents currently approved for use in moderate/severe psoriasis are infliximab, a chimeric neutralising monoclonal antibody, adalimumab, a fully humanised IgG1 monoclonal antibody, and etanercept, a recombinant fusion protein comprising an Fc domain of human IgG1 monoclonal antibody and the ligand binding domain of the TNFα receptor.
Since the characterisation of a dominant pathogenic role for the IL-23/T17 axis in psoriasis by genome-wide association studies (GWAS), several drugs targeted against components of this pathway have been studied with reported successful outcomes (Fig. 3). Ustekinumab is a Food and Drug Administration (FDA)-approved humanised monoclonal antibody that neutralises the p40 subunit common to IL-23 and IL-12. The antibody prevents the binding of IL-23 and IL-12 to their receptors, thus inhibiting T17 and Th1 signalling pathways.
IL-17A is a central driver in disease pathogenesis; hence, IL-17 inhibitors have been extensively researched for the treatment of psoriasis. Secukinumab and ixekizumab are neutralising humanised monoclonal antibodies (IgG4 and IgG1, respectively) that bind to IL-17A and brodalumab binds to the IL-17 receptor A subunit. Secukinumab received FDA approval for the treatment of moderate/severe psoriasis in January 2015. Brodalumab has a potentially wider range of action as it antagonises the receptor that binds IL-17A, IL-17F and IL-17A/F heterodimers.
The oral phosphodiesterase-4 (PDE-4) inhibitor apremilast prevents the conversion of 3′-5′-cyclic adenosine monophosphate (cAMP) to AMP. Its beneficial effect is thus attributable to increased levels of cAMP, which reduces inflammation by downregulating cytokines such as TNFα and IL-23. It also upregulates the production of anti-inflammatory molecules such as IL-10.
Janus kinases (JAK) are cytoplasmic protein tyrosine kinases that mediate the activation of STAT proteins. JAK/STAT intracellular signalling regulates the expression of proinflammatory genes. Numerous cytokines that are upregulated in psoriatic skin lesions and involved in T cell proliferation, activation and survival, such as type I and III IFNs and IL-23, use the JAK/STAT pathway; however, there are some exceptions, including TNFα and IL-17.
A3 adenosine receptors (A3AR) are G protein coupled receptors that bind to adenosine. They were found to be highly expressed in peripheral blood mononuclear cells from psoriasis patients. Activation of A3AR by the agonist CF101 has been shown to reduce NF-κB signalling and promote apoptosis of inflammatory cells. Pro-inflammatory cytokines such as TNFα, IL-6 and IL-12 are also downregulated.
Given the potential importance of dysregulated IL-1 signalling in the pathogenesis of pustular psoriasis, IL-1 blockers have been investigated for use in the treatment of this clinical phenotype, with successful cases described.
The immunotherapy method for psoriasis act faster, more effectively and in a more targeted manner.