Psoriatic Arthritis: Research Into Inflammatory Effects May Lead to Better Treatments

Psoriatic arthritis (PsA) is a chronic, inflammatory autoimmune condition characterized by inflamed joints. PsA often, but not always, occurs in people who also have psoriasis, an autoimmune skin condition that results in scaly, red itchy patches.

PsA can affect the larger joints, such as the knees and shoulders. But it also can occur in the fingers, toes, back or pelvis. Symptoms usually start between ages 30 and 50, and can lead to mild symptoms or chronic inflammation that may result in joint damage -- if not treated.

Men and women are equally at risk. However, women tend to experience more serious outcomes, possibly because they are diagnosed 10 years later than men, on average, allowing the disease to advance before treatment is started.

Now, a breakthrough study has found a potential new way of fighting PsA inflammation. In recent research published in Nature Immunology, an international group of scientists from Spain, Germany, and England focused on how cytokines affect joints—and how inflammation is reversed. Cytokines refer to a type of protein that is made by certain immune and non-immune cells. They have an effect on the immune system. Some cytokines stimulate the immune system and others slow it down.

Alex Mafdali, M.D., a primary care sports medicine physician with Baptist Health Orthopedic Care..

In a first, the group of international researchers were able to see specific connective tissue cells called “CD200+ fibroblast” shift from being pro-inflammatory to anti-inflammatory behavior when “disease-modifying anti-rheumatic drugs” -- or DMARDs -- were introduced, resulting in less inflammation and pain in the joints of both animals and humans.

“By advancing our understanding of fibroblast biology and developing new ways to manipulate the cells, researchers may pave the way for innovative treatments that not only reduce inflammation -- but also prevent joint destruction in arthritic patients,” explains Alex Mafdali, M.D., a primary care sports medicine physician with Baptist Health Orthopedic Care.

Fibroblasts are connective tissue cells with that can help build strong joints by producing collagen, helping maintain the structure of tissues, and playing a role in the healing of wounds. They also play a part in your immune system. In the case of psoriatic arthritis, fibroblasts may play a part in releasing pro-inflammatory cytokines which will induce the recruitment and activation of other immune cells.

Now, for the first time, the researchers found that fibroblasts can change their phenotype — or their behavior — after common PsA medications, or DMARDs. were used to block the inflammatory action of cytokines in the joint. The fibroblasts then switched from pro-inflammatory to more anti-inflammatory, resulting in less inflammation and pain in the joints.

Without the cytokines, the overactive fibroblasts calmed down and changed their behavior to work on calming joint inflammation instead of causing it.

“When a fibroblast changes its phenotype, it alters its characteristics and behavior in response to specific signals or conditions,” said Dr. Mafdali. “These changes enable the cell to perform different functions, such as healing wounds, responding to inflammation, or contributing to chronic diseases.”

The study found that in conditions like rheumatoid arthritis (RA), PsA, and spondyloarthritis, “the cells that repair and maintain connective tissues (fibroblasts) become overly active and contribute to inflammation and damage,” Dr. Mafdali said. “This happens in the joints, where tendons attach to the bones and in the bones themselves. However, when patients are treated with drugs that block certain inflammatory proteins, [we now know that this overactivity of fibroblasts is reversed, helping to reduce inflammation and promote healing.”

The research finding may lead to a new type of PsA medication. One day, medications for PsA or other inflammatory joint diseases may target fibroblasts themselves.

“Understanding these mechanisms opens potential avenues for therapeutic strategies targeting specific fibroblast populations to treat inflammatory arthritis,” explains Dr. Mafdali.