New results in psoriatic research

by | Oct 29, 2021 | Blog, Skin disease | 0 comments

On the International Day of Psoriasis, we wanted to collect the latest results in the field of the psoriatic research that allow us to continue advancing in the knowledge and treatment of this skin disease.

Symptoms

Psoriasis is a chronic, inflammatory disease of the skin. As we explained in a previous post, psoriasis is manifested by the appearance of red plaques accompanied by whitish peeling repeatedly over time, these plaques can occur anywhere on the body, however, the elbow , knees and scalp are more prone areas.

Related to the development of psoriatic plaques, the latest published research indicates that these are produced, on the one hand, by the hyperproliferation of keratinocytes and, on the other, by inflammation of the epithelium. Both processes appear to be mediated by the phosphatidylinositol 3-kinase (PI3K)-dependent signalling pathway. The PI3Kδ isoform is overexpressed in psoriatic plaques, and it also accumulates in proliferating keratinocytes, prolonging hyperproliferation and inducing epidermal inflammation via IL-22 [1].

In addition to IL-22, there are other interleukins that have recently been associated with psoriasis. In this sense, it has been shown that IL-17A is increased in psoriatic lesions and is essential for the pathogenesis of this disease. Similarly, IL-19, along with other cytokines of the IL-20 subfamily, such as IL-20 and IL-24, are induced by IL-17A and contribute to the appearance of psoriatic plaques [2].

 

Image from Hans Braxmeier in Pixabay

The production of these cytokines is carried out by the keratinocytes themselves. Specifically, those that express FRA1, a transcription factor of the AP-1 family composed of transcription factors belonging to the families of c-Fos, c-Jun, ATF and JDP [3]. Increased release of these pro-inflammatory cytokines induces proliferation of keratinocytes and inflammation of the epidermis that bring up psoriatic plaques [4].

Genetics

Psoriasis does not have as strong a genetic component as atopic dermatitis. However, recent investigations have proposed some genes as potential markers for the detection and prognosis of psoriasis.

An example of this is the evaluation of the levels of interleukin IL-18 and sE-selectin, a soluble cell adhesion molecule, in the gingival crevicular fluid. In people with psoriasis, the levels of IL-18 were elevated, while those of sE-selectin were lower than the levels of this molecule in the gingival crevicular fluid of healthy people [5].

Another example of an interleukin that can be used as a biomarker for psoriasis is IL-31. The levels of this interleukin in the blood serum are not decisive in relation to the evolution of psoriatic pruritus or itching. On the contrary, different polymorphisms in the IL-31 promoter seem to be related to an increased risk of psoriasis. Specifically, the -1066 AA genotype of the IL-31 gene is more common in patients with psoriasis, while the GG genotype as well as the G allele of the IL-31-2057 gene polymorphism are rarely observed in these patients [6].

Image from Darwin Laganzon in Pixabay

Apart from interleukins, there are other types of molecules that can be used as biomarkers of psoriasis [7]. In this sense, in blood serum we can quantify:

  • Adipokines such as resistin and adiponectin.
  • Antimicrobial peptides such as defensin 2 and S100A.
  • Protease inhibitors such as squamous cell carcinoma antigen and elafin in the blood.
  • Glycoproteins such as leucine-rich alpha-2-glycoprotein and YKL-40.
  • Fatty acid binding protein.

Treatments

Psoriasis is a disease that has no cure. However, the different treatments available today seek to minimize the signs of psoriasis and improve the quality of life. In this way, we find from topical treatments directed for cases of mild psoriasis, to systemic treatments for the most severe cases of psoriasis.

The latest research opens new paths in which to develop innovative treatments for the disease. Like, for example, the modulation of the skin’s microbiome.

The microbiome is made up of different microorganisms that conform the flora of a certain tissue and play an important role in its homeostasis. The microbiota of the skin is altered in psoriatic lesions, presenting a greater abundance of the bacteria Streptococcus spp., Corynebacterium spp., Cutibacterium spp., Staphylococcus spp., Finegoldia spp. and Neisseria spp. Regarding the role of the intestinal microbiome in the pathogenesis of psoriasis, patients suffering from this disease have a greater amount of Bacteroidetes and decreased levels of Firmicutes, Proteobacteria and Actinobacteria. All this alters the integrity of the intestinal barrier, the response of the T cells and the balance of the microbiota [8].

To re-establish the balance of the gut microbiota and evaluate its effect on psoriasis symptoms, several studies were conducted in which probiotics and prebiotics were administered in patients with the disease. On the one hand, Vijayashankar and Raghunath observed how a probiotic with Lactobacillus sporogenes for 15 days alleviated the symptoms that accompany the sudden onset of pustular psoriasis in a 47-year-old patient [9]. On the other hand, Groeger et al. showed a significant decrease in the levels of two biomarkers of the disease: CRP (c-reactive protein) and TNF-α in the blood serum of patients with psoriasis after the administration of a probiotic with Bifidobacterium infantis 35264 for 8 weeks [10].

Image from Edward Jenner in Pexels

In severe cases of psoriasis, systemic treatment is advisable. New systemic treatments include Janus kinase (JAK) inhibitors. These compounds inhibit the intracellular JAK / STAT signal pathway, blocking the transcription of genes for proinflammatory cytokines crucial in the pathogenesis of psoriasis [11].

JAK inhibitors are divided into two main types:

  • The first generation of JAK inhibitors target two or more different JAKs. These treatments were approved for psoriasis in the early 2010s.
  • The second generation is more specific, targets only one type of JAK, and has fewer side effects than the first generation.

Second-generation JAK inhibitors have been tested with satisfactory results in other dermatological diseases such as atopic dermatitis and alopecia aerata [12]. This opens new opportunities for the treatment of the most serious cases of these skin diseases.

References

  1. Mercurio L, Morelli M, Scarponi C, Scaglione GL, Pallotta S, Albanesi C, Madonna S. PI3Kδ Sustains Keratinocyte Hyperproliferation and Epithelial Inflammation: Implications for a Topically Druggable Target in Psoriasis. Cells. 2021; 10(10):2636.
  2. Xu X, Prens E, Florencia E, Leenen P, Boon L, Asmawidjaja P, Mus AM, Lubberts E. Interleukin-17A Drives IL-19 and IL-24 Expression in Skin Stromal Cells Regulating Keratinocyte Proliferation. Front Immunol. 2021 Sep 20; 12:719562.
  3. Karin M, Liu Zg, Zandi E. AP-1 function and regulation. Curr Opin Cell Biol. 1997 Apr;9(2):240-6.
  4. Zolotarenko A, Chekalin E, Piruzian E, Bruskin S. FRA1 mediates the activation of keratinocytes: Implications for the development of psoriatic plaques. Biochim Biophys Acta Mol Basis Dis. 2018 Dec;1864(12):3726-3734.
  5. Valenzuela F, Fernández J, Jiménez C, Cavagnola D, Mancilla JF, Astorga J, Hernández M, Fernández A. Identification of IL-18 and Soluble Cell Adhesion Molecules in the Gingival Crevicular Fluid as Novel Biomarkers of Psoriasis. Life. 2021; 11(10):1000.
  6. Purzycka-Bohdan D, Gleñ J, Zabłotna M, Nedoszytko B, Szczerkowska-Dobosz A, Sokołowska-Wojdyło M, Rêbała K, Nowicki RJ. Significance of interleukin-31 (IL-31) gene polymorphisms and IL-31 serum level in psoriasis in correlation with pruritus. Postepy Dermatol Alergol. 2021 Aug;38(4):657-664. doi: 10.5114/ada.2021.108926. Epub 2021 Sep 17.
  7. Honma M, Nozaki H. Molecular Pathogenesis of Psoriasis and Biomarkers Reflecting Disease Activity. J Clin Med. 2021;10(15):3199. Published 2021 Jul 21.
  8. Polak K, Jobbágy A, Muszyński T, Wojciechowska K, Frątczak A, Bánvölgyi A, Bergler-Czop B, Kiss N. Microbiome Modulation as a Therapeutic Approach in Chronic Skin Diseases. Biomedicines. 2021; 9(10):1436.
  9. Vijayashankar, M.; Raghunath, N. Pustular Psoriasis Responding to Probiotics—A New Insight. Our Dermatol. Online2012, 3, 326–329.
  10. Groeger, D.; O’Mahony, L.; Murphy, E.F.; Bourke, J.F.; Dinan, T.G.; Kiely, B.; Shanahan, F.; Quigley, E.M. Bifidobacterium infantis 35624 modulates host inflammatory processes beyond the gut. Gut Microbes 2013, 4, 325–339.
  11. Słuczanowska-Głąbowska S, Ziegler-Krawczyk A, Szumilas K, Pawlik A. Role of Janus Kinase Inhibitors in Therapy of Psoriasis. J Clin Med. 2021;10(19):4307. Published 2021 Sep 22.
  12. Damsky W, King BA. JAK inhibitors in dermatology: The promise of a new drug class. J Am Acad Dermatol. 2017;76(4):736-744.

Cover Image from Kristina Nor in Pexels

 

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