IFPA World PsO and PsA Conference

The International Federation of Psoriasis Associations (IFPA) hosted its 7th World Psoriasis and Psoriatic Arthritis Conference in late June in Stockholm, Sweden. Topics covered included genetics/immunology, prevention of psoriatic arthritis, understanding pain and itch, treatment advances in topical therapies and phototherapy, and mental health in psoriatic disease.

“As a clinical and research community, we strive to advance the care for patients living with psoriatic diseases, which encompasses not only psoriasis and psoriatic arthritis, but also other comorbid conditions that impact our patients’ lives,” said Conference President April Armstrong, MD, MPH.

Wilson Liao, MD, Director of the University of California San Francisco Psoriasis and Skin Treatment Center, gave the keynote presentation, “Advances in Genetics and Immunology of Psoriatic Arthritis.” In it, Liao noted that it may soon be possible to achieve remission and cure for all psoriasis patients. 

“The key is really to understand the fundamental biology of psoriasis through both genetics and immunology,” he said.

Sixteen years ago, Liao said, only three psoriasis genetic loci had been identified; as of this year, 109 have been discovered. The largest genetic study to date was a collaboration among universities around the world on a meta-analysis of 18 genome-wide association studies (GWAS) with 36,466 cases and 458,078 controls. While the IL-17/IL-23 and TNF pathways had already been understood to a certain degree, the study unearthed more information. 

“What was really new and interesting from this study is that the aryl hydrocarbon receptor (AhR) gene also lit up as a psoriasis gene; as you all know, that is the target of the new topical drug tapinarof,” Liao said. “We also saw that the antigen presentation pathways are extremely important, with the largest hit, of course, being in the HLA region. We also saw new genes in the innate immune system regarding our innate response to viral antigens, possibly hinting at some triggers for psoriasis.”

Liao noted that genetics can help to better understand genotype/phenotype correlations and help predict comorbidities, such as psoriatic arthritis. A University of Michigan study, he noted, has developed a machine learning model to predict psoriatic arthritis with accuracy of approximately 80%.1 Liao also discussed the impact of gaining a deeper understanding in recent years of the immunology and biology of psoriasis through single-cell and spatial technologies. 

“In single-cell technologies, you take a biopsy of psoriatic skin, dissociate the individual cells, bar code and label the cells, and you can sequence them to get the transcriptone of every individual cell and then perform future analyses,” he said. “In spatial technologies, you also take a biopsy of psoriatic skin, embed it either in FFPE or just in a frozen section, and then you can actually probe tiny dots on the slide from a few to thousands of transcripts, thereby understanding how the transcriptone fits within the architecture of psoriatic tissue and better understand cell-cell interactions.”

These technologies have helped researchers understand, among other things, the importance of fibroblasts. For example, a 2023 study by Ma et al found that SFRP2+ fibroblasts are actively involved in secreting chemokines such as CCL13, CCL19, and CXCL12 to interact with surrounding myeloid, dendritic, T17, and keratinocyte cells that amplify the psoriatic inflammation.2 Another 2023 study, by He et al, found that two of the five fibroblast subtypes—clusters 3 and 4—were more active in psoriatic patients, and that those two clusters interacted with keratinocytes and endothelial cells.3

“We now can build upon the basic model of just T cells, APCs, and keratinocytes, and now it is more refined with our understanding of fibroblasts, endothelial cells, and other cell types,” Liao said. “We have seen how TCR sequencing does confirm the presence of these clonal expansions within the IL17-producing population. And psoriasis may be triggered by not only Group A Streptococcus and ADAMTSL5, but parallels to those antigens like self-lipids as well as wheat, tobacco, and other microbial antigens.” n

1. Patrick MT et al. Genetic signature to provide robust risk assessment of psoriatic arthritis development in psoriasis patients. Nat Commun. 2018;9:4178. https://doi.org/10.1038/s41467-018-06672-6.

2. Ma F et al. Single cell and spatial sequencing define processes by which keratinocytes and fibroblasts amplify inflammatory responses in psoriasis. Nat Commun. 2023 Jun 12;14(1):3455. doi: 10.1038/s41467-023-39020-4.

3. He CC, Song TC, Qi RQ, Gao XH. Integrated single-cell and spatial transcriptomics reveals heterogeneity of fibroblast and pivotal genes in psoriasis. Sci Rep. 2023 Oct 10;13(1):17134. doi: 10.1038/s41598-023-44346-6.