Understanding the Different Pathways Involved in PsA and Psoriasis

A novel single nucleotide polymorphism (SNP) of a potent inhibitor of T cell activation has been associated with susceptibility to psoriatic arthritis, but not psoriasis, according to a new study.

Psoriatic arthritis is estimated to have a larger genetic component than psoriasis, however, genetic factors known to contribute to the susceptibility of psoriatic arthritis are not fully understood.  Recent studies have identified psoriatic-arthritis specific loci that begin to explain the difference in the genetic architecture of the two diseases, according to a recent study published in the Annals of the Rheumatic Diseases.[[{"type":"media","view_mode":"media_crop","fid":"41778","attributes":{"alt":"©lculig/Shuttersstock.com","class":"media-image media-image-right","id":"media_crop_6139461589045","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"4443","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":"","typeof":"foaf:Image"}}]]

Now, for the first time, researchers, led by Anne Barton, PhD, of the University of Manchester, Manchester, UK, report a genome-wide significant association of the rs2476601 variant in the PTPN22 gene with susceptibility to psoriatic arthritis consistent with reports in many other autoimmune diseases, but with no evidence for association to psoriasis.

PTPN22 affects the responsiveness of T and B cell receptors, and mutations are associated with increases or decreases in risks of autoimmune diseases.

The researchers selected 15 SNPs for validation genotyping in 1,177 cases and 2,155 controls. Meta-analysis of Immunochip and validation data sets consisted of 3,139 psoriatic arthritis cases and 11,078 controls. Novel psoriatic arthritis susceptibility loci were compared with data from two large psoriasis studies to determine psoriatic arthritis specificity.

They found a genome-wide significant association to rs2476601, mapping to PTPN22, but no evidence for association in the psoriasis cohort. The effect estimates were significantly different between psoriatic arthritis and psoriasis.

“The identification of PsA-specific loci is vital in terms of understanding the different pathways involved, which may require different treatments, and for future screening strategies to identify subjects at risk of developing PsA in patients with psoriasis,” the researchers wrote.

In addition, researchers also confirmed the association of psoriatic arthritis with a previously reported psoriasis locus, NOS2.

This brings the total number of confirmed, genome-wide significant psoriatic arthritis loci to 10, including 4 that are psoriatic arthritis-specific (HLA-B, chromosome 5q31, PsA-specific variants within IL23R) and now PTPN22, they wrote.

References:

John Bowes, Sabine Loehr, et al. PTPN22 is associated with susceptibility to psoriatic arthritis but not psoriasis: evidence for a further PsA-specific risk locus. Annals of the Rheumatic Diseases.  Online first April 28, 2015. doi:10.1136/annrheumdis-2014-207187