It was already known that the disease had a number of genetic predispositions, one of which controls how immune cells called T cells see antigen molecules from disease-causing microorganisms.
However, it is not understood exactly what triggers the onset of psoriatic arthritis in patients. Using cutting edge single cell technology, the researchers analysed thousands of individual immune cells from fluid drained from the knees of patients with psoriatic arthritis.
They could see which genes were switched on in each cell and showed these T cells had an activated inflammatory profile. The researchers also amplified and sequenced the RNA from receptor genes, to identify active T cell receptors in each cell. The study showed that many T cells in the joint fluid shared an identical T cell receptor and were therefore clones of each other. These were very likely to have been triggered to reproduce themselves by a particular antigen.
Using machine learning to compare these receptors from different patients, they discovered that the expanded clones of T cells were potentially recognising something in common. These cells also shared other markers, including a receptor called CXCR3, that directed them to the inflammation site.
Each receptor is like a unique lock that recognises a molecular key and we discovered, that across the patients, they are recognising a common molecule. This gives the first evidence that the T cells are seeing and reacting to the same molecule, which acts as a trigger for the disease.
We don't know the exact culprit yet, but this a great step forward in understanding the disease. The large-scale single cell data from the joints and blood of psoriatic arthritis patients were then used to investigate how the T cells could transfer from the blood to the joint to cause the damage. It is helping us to understand the intricate mechanisms behind psoriatic arthritis, including starting to unravel the signals that tell the T cells to cross over into the joint fluid.
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The distal interphalangeal joints are those closest to the nails. Nail changes are especially frequent with this form of psoriatic arthritis. The asymmetric oligoarticular and symmetric polyarthritis types are the most common forms of psoriatic arthritis. The asymmetric oligoarticular type of psoriatic arthritis involves different joints on each side of the body, while the symmetric polyarthritis form affects the same joints on each side.
Any joint in the body may be affected in these forms of the disorder, and symptoms range from mild to severe. Some individuals with psoriatic arthritis have joint involvement that primarily involves spondylitis, which is inflammation in the joints between the vertebrae in the spine. Symptoms of this form of the disorder involve pain and stiffness in the back or neck, and movement is often impaired.
Joints in the arms, legs, hands, and feet may also be involved. The most severe and least common type of psoriatic arthritis is called arthritis mutilans. Fewer than 5 percent of individuals with psoriatic arthritis have this form of the disorder. Arthritis mutilans involves severe inflammation that damages the joints in the hands and feet, resulting in deformation and movement problems. Bone loss osteolysis at the joints may lead to shortening telescoping of the fingers and toes.
Neck and back pain may also occur. Between 5 and 10 percent of people with psoriasis develop psoriatic arthritis, according to most estimates. Some studies suggest a figure as high as 30 percent. Psoriasis itself is a common disorder, affecting approximately 2 to 3 percent of the population worldwide. The specific cause of psoriatic arthritis is unknown. Its signs and symptoms result from excessive inflammation in and around the joints.
Inflammation occurs when the immune system sends signaling molecules and white blood cells to a site of injury or disease to fight microbial invaders and facilitate tissue repair.
When this has been accomplished, the body ordinarily stops the inflammatory response to prevent damage to its own cells and tissues. Mechanical stress on the joints, such as occurs in movement, may result in an excessive inflammatory response in people with psoriatic arthritis. The reasons for this excessive inflammatory response are unclear. Researchers have identified changes in several genes that may influence the risk of developing psoriatic arthritis.
The most well-studied of these genes belong to a family of genes called the human leukocyte antigen HLA complex. The HLA complex helps the immune system distinguish the body's own proteins from proteins made by foreign invaders such as viruses and bacteria.
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