Immune system connection with psoriatic arthritis: An overview
Psoriatic arthritis (PsA) is a chronic, painful condition that affects the joints, and can occur in anyone at any age. A key characteristic of PsA is the loss of self-tolerance, leading to autoimmunity, where the immune system mistakenly attacks healthy tissues.
Causes and Underlying Mechanisms
The loss of self-tolerance in PsA arises from keratinocyte-induced inflammatory signaling, innate and adaptive immune cell activation, and defective immune regulation by T-regulatory cells (Tregs). Key contributing factors include:
- Excessive CXCL10 secretion from keratinocytes, leading to joint inflammation.
- Dysregulated immune cell subsets, such as Th cells and macrophages, producing inflammatory cytokines like IL-17A and TNF-α.
- Reduced numbers and impaired suppressive function of Tregs, contributing to loss of immune regulation and persistent inflammation.
Genetic and environmental triggers, such as infections and genetic predispositions, can also influence autoimmunity development.
Treatment and Prevention
Treatment for PsA focuses on slowing disease progression, with the aim of protecting not only the joints and tendons, but also other organs that autoimmune responses may damage. Doctors use various medications, including Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), corticosteroids, Disease-Modifying Anti-Rheumatic Drugs (DMARDs), and biologics.
However, an increased likelihood of developing serious infections has been reported with all types of DMARDs used to treat PsA, but the risk may be higher with biologics. Certain precautions can reduce this risk, such as antiviral treatment for people with hepatitis B, updating vaccinations, and discontinuing certain DMARDs during active infections.
Targeting key inflammatory pathways, such as TNF-α and IL-17A, has become a mainstay in PsA therapy. JAK-STAT pathway inhibitors are also used to block upstream signaling events, thereby reducing inflammation and autoimmunity.
Understanding the role of keratinocyte-immune crosstalk and Treg dysfunction offers new avenues for prevention, such as modulating skin inflammation early or restoring Treg function to maintain self-tolerance before joint disease ensues.
Lifestyle Factors
Adults with a body mass index (BMI) of 25 or higher are advised to follow a calorie-restricted diet and increase their physical activity levels. Weight loss in adults with PsA and obesity is associated with a reduction in disease activity, inflammation, and pain. Greater adherence to a Mediterranean diet correlates with lower disease activity in people with PsA.
Complications
Some of the most common immune-mediated complications of PsA include inflammatory bowel disease, autoimmune eye diseases, heart disease, metabolic diseases such as diabetes, and cancer. People with psoriatic diseases, including PsA, are developing health complications related to tissue damage in other parts of the body.
If someone receiving treatment for PsA begins showing symptoms of illness, such as fever or cough, they should contact a doctor right away.
Prevalence and Risk Factors
PsA is most commonly observed in people who already have psoriasis. If you have psoriasis and are experiencing joint pain, stiffness, or other symptoms, it's important to discuss these symptoms with your doctor.
Conclusion
While the complex immune dysregulation in PsA presents challenges, advancements in our understanding of the disease's underlying mechanisms offer hope for improved treatments and prevention strategies. By targeting key inflammatory pathways and exploring new avenues for prevention, we can work towards better management and control of this chronic condition.
- The immune system's mistaken attack on healthy tissues in psoriatic arthritis (PsA) is due to keratinocyte-induced inflammatory signaling, immune cell activation, and T-regulatory cell dysfunction.
- Excessive CXCL10 secretion from keratinocytes and dysregulated immune cell subsets like Th cells and macrophages contribute to PsA by producing inflammatory cytokines.
- Reduced numbers and impaired suppressive function of T-regulatory cells in PsA lead to loss of immune regulation and persistent inflammation.
- Genetic and environmental factors, including infections and genetic predispositions, can influence the development of autoimmunity in PsA.
- Treatment for PsA focuses on slowing disease progression using drugs like Non-Steroidal Anti-Inflammatory Drugs (NSAIDs), corticosteroids, Disease-Modifying Anti-Rheumatic Drugs (DMARDs), and biologics.
- The risk of serious infections may be higher with biologics used to treat PsA; certain precautions can reduce this risk, such as antiviral treatment for people with hepatitis B, updating vaccinations, and discontinuing certain DMARDs during active infections.
- Targeting key inflammatory pathways like TNF-α and IL-17A, and using JAK-STAT pathway inhibitors, have become important strategies in PsA therapy.
- Adults with psoriatic arthritis and obesity who follow a calorie-restricted diet and increase physical activity levels may experience a reduction in disease activity, inflammation, and pain.
- People with psoriatic arthritis are at an increased risk of developing health complications such as inflammatory bowel disease, autoimmune eye diseases, heart disease, metabolic diseases like diabetes, and cancer.
