The two patient cohorts shared similar characteristics, with comparable baseline demographics, disease characteristics, and skin histopathology, and all the samples were fed into identical analyses. After both 1 and 12 weeks of treatment, the neutralisation of activity of relevant transcriptomic genes following high-dose guselkumab was significantly more extensive than that with ustekinumab unpublished data. These data were further supported in a real-time PCR analysis of the DEFB4 and LCN2 gene products, showing that these ILresponsive antimicrobial proteins recovered to a greater extent with guselkumab versus ustekinumab.
From Evolution to Revolution: IL-23 in the Treatment of Psoriasis Patients
These observations prompt the question of the relative potency of guselkumab and ustekinumab, and data show that, across a range of assays, there is a 2—fold difference in potency in favour of guselkumab. There are several factors that could contribute to the superiority of guselkumab over ustekinumab in neutralising psoriasis-related gene expression. In a mouse model of ILmediated inflammatory activity in skin, knockout of the IL subunit p40 resulted in inflammation, thin skin, and a doubling in transepidermal water loss. In addition, there is complexity within the IL family of cytokines, and gene expression data reveal a possible role for other, less well-characterised members.
As well as changes in the levels of various members of the IL family, such as K16, ILA, p19, and p40, psoriasis is also associated with raised IL unpublished data. IL is composed of the subunits p28 and Ebi3 named for homology to an Epstein—Barr virus gene , 25 neither of which are targeted by guselkumab or ustekinumab.
As the IL cytokine family is promiscuous and protein subunits of the family can combine with different partners to activate other pathways, Ebi3 could pair with p19 to form IL Moreover, p40 can pair with p28 to form IL-Y, 7 which has anti-inflammatory activities; therefore, it is possible that some of the benefits of blocking IL and IL activity could be reduced by downregulating beneficial IL-Y activity. Furthermore, there may be functional plasticity in the Th17 lineage, such that removal of IL from pathogenic T cells can convert them to non-pathogenic, regulatory T cells.
In summary, although molecular data have shown very clear differential effects of guselkumab and ustekinumab on the transcriptome of psoriasis-associated cells, other potential cytokine activities in psoriasis still require full characterisation. In patients with psoriasis receiving anti-IL treatment, a positive response to continuous treatment can be very long-lasting.
As noted, evidence for the latter originates from disease memory in clinically healed skin, which shows relatively high levels of ILproducing T cells. Relapse following discontinuation of ILR blockade generally occurs within a few weeks, 33 suggesting that blockade of IL rather than its receptor may be a more efficacious long-term approach. How can we effectively assess the effects on IL and ILproducing skin-resident memory T cells present in non-lesional tissue?
Following treatment discontinuation, psoriasis tends to revert to its baseline severity. In addition, single nucleotide polymorphisms in ILR are associated with autoimmune disease, including psoriasis, and ILR is preferentially expressed in these skin cells in psoriasis patients. Possibilities for purging memory T cells include antibody-dependent cell-mediated cytotoxicity or lack of stimulus through ILR, though evidence for any of the available drugs exerting either mechanism in non-lesional skin is lacking.
In conclusion, multiple observations suggest disease modification in patients with psoriasis receiving anti-IL treatment: a clinical effect beyond drug half-life and biological half-life of the treatment, possible effects on skin-resident memory T cells that mediate disease memory, and the effect of blocking only pathogenic not non-pathogenic Th17 cells.
Login to continue
Recent evidence has revealed that CNS autoimmunity might be triggered in the gut-associated lymphoid system by interaction with the intestinal bacterial flora microbiota. Compared to animal studies on T cells in EAE, research into the role of T cells in human MS faces particular limitations, such as reduced accessibility of biological materials eg, CNS tissue and CSF , genetic heterogeneity of the human population, and ethical restrictions of in vivo research with human participants.
- The Confessions of St. Augustine (Paraclete Essentials)?
- Open the Mind Exercise the Soul: Life from a Psychic Point of View.
- Perspective ARTICLE.
- Mrs. General Talboys [with Biographical Introduction]!
Recent technological advances, including multidimensional immune phenotyping and single-cell genome-wide transcriptomics, are expected to offer new insights regarding the role of different types of T cells. Melvin S. Seymour Reichlin. Thomas R. Home Contact us Help Free delivery worldwide. Free delivery worldwide.
- Le Monde Des Morts (French Edition).
- Genetic Models of Immune and Inflammatory Diseases | Abul K. Abbas | Springer.
- Systemic lupus erythematosus;
- Systemic lupus erythematosus;
- Original Research ARTICLE.
Bestselling Series. Harry Potter.
- Works of Stanley Waterloo.
- Cheesecake Recipes?
- Bibliographic Information?
- Lannée poétique (French Edition).
Popular Features. New Releases. Genetic Models of Immune and Inflammatory Diseases. The advent of methods for introducing genes into the germlines of mice, and for targeted disruption of particular genes by homologous recombination, has provided scientists in many disciplines with an extraordinarily powerful set of analyti- cal tools. Some of the most informative applications of transgenic and gene knockout technology have been in studies of lymphocyte development and activation.
The goal of this symposium was to bring together investigators using these genetic approaches for analyzing the immune system, with a view to defining common themes and novel directions. Transgenic mice have a wide variety of important applications in immu- nology.
Systemic lupus erythematosus | Nature Reviews Disease Primers
Defined proteins can be expressed in selected tissues throughout development, thus acquiring the essential characteristic of "self" antigens. Such models have been used to study how immune responses to these artificially created "self" antigens are controlled. Antigen receptors of lym- phocytes have been expressed as transgenes, and because lymphocytes are endowed with the unique property of allelic exclusion, such transgenic mice become essentially monospecific. Immunomodulatory agents have been expressed in defined tissues or throughout the body, providing tools for studying the functional consequences of dysregulated expression of biologi- cal response modifiers.
Product details Format Paperback pages Dimensions x x Other books in this series. Add to basket. Acromegaly Richard J.