C5orf30 Gene is a Negative Regulator of Tissue Damage in Rheumatoid Arthritis Save

PNAS has reported the work of an international team of scientists from the University College Dublin and the University of Sheffield, who have studied DNA samples and biopsy samples from joints of over 1,000 rheumatoid arthritis patients in the UK and Ireland and determined the C5orf30 gene to be a negative regulator of RA severity (Citation source  http://buff.ly/1PG8ynK).

Previous research has shown the variant rs26232 in the first intron of the C5orf30 (chromosome 5 open reading frame 30) gene to be associated with both risk of developing RA and the odds of developing severe RA, including radiographic damage to joints.

They report that C5orf30 encodes a 206-aa protein that is highly expressed in RA synovial fibroblasts (RASFs). Importantly, inhibition of C5orf30 increases the autoaggressive phenotype of RASFs in vitro and increases joint inflammation and damage in murine inflammatory arthritis. RASFs lacking C5orf30 exhibit increased cell migration and invasion in vitro, and gene profiling following C5orf30 inhibition confirmed up-regulation of genes involved in cell migration, adhesion, angiogenesis, and immune and inflammatory pathways. Loss of C5orf30 contributes to the pathology of inflammatory arthritis in vivo, because inhibition of C5orf30 in the collagen-induced arthritis model markedly accentuated joint inflammation and tissue damage.

Thus, C5orf30 is a negative regulator autoaggressive RASFs and tissue damage. Patients with this gene are likely to suffer the severest effects of the condition and can now be identified early, allowing patients to be fast-tracked to the more aggressive treatments.