Mutated gene is the driver of psoriasis

What causes psoriasis? Researchers might have just found the answer.

In a recent paper, researchers at The Australian National University (ANU; Australia) have discovered that a mutated gene is responsible for the chronic inflammatory skin condition, psoriasis. This world-first discovery could offer new hope for psoriasis patients.

Psoriasis is characterized by red, scaly and itchy patches of skin. While for some it is a minor irritation, for others the condition can be debilitating, causing extreme pain and discomfort. This is particularly true for psoriasis patients who develop pain and swelling in their joints, known as psoriatic arthritis. Currently, there is no cure for psoriasis, so treatment helps manage the condition.

Psoriasis and psoriatic arthritis are both forms of autoimmune disease, where the immune system mistakenly attacks healthy cells. Until now, the mechanisms that drive inflammation in psoriasis have remained largely unknown.

Using a mouse model, the team at ANU investigated the impact of gain-of-function mutation in the IKBKB gene; this gene has previously been linked to immune deficiency. Mice with a single copy of the mutant gene were found to develop psoriasis but, interestingly, mice with two copies went on to further develop characteristics of psoriatic arthritis.

Single-cell RNA sequencing and phenotypic analysis then identified that the mutant IKBKB gene resulted in the abnormal function of a group of immune cells, known as regulatory T cells.

“These cells are normally considered gatekeepers of the immune system”, commented the first author of the study, Dr Chelisa Cardinez. “However, we found that this mutation alters the function of these cells, causing them to contribute to inflammation and promote the onset of disease.”

Strikingly, the group of regulatory T cells affected show a predilection for the skin, bone marrow and joints.

The findings from this study open the door to new, improved diagnosis and treatment for psoriasis patients.

Dr Cardinez notes: “Studies have shown that delays in psoriatic arthritis diagnosis is linked to worse clinical outcomes for patients. Therefore, earlier detection and treatment of these immune diseases is key to improving health outcomes.”

“By developing a better understanding of the IKBKB gene and the role it plays in promoting the onset of these diseases, it could bring us a step closer to one day finding a cure.”