connection between ACPA and rheumatoid arthritis: Important insights to understand
Rewritten Article:
The immune system generates anti-citrullinated protein antibodies (ACPAs) to tackle citrullinated proteins. These ACPAs aid doctors in diagnosing early-stage rheumatoid arthritis (RA) and predicting the likelihood of bone erosion.
RA is an autoimmune disease, where the immune system attacks the body's own tissues in error, leading to joint pain, rigidity, and swelling. Even though the causes of RA remain uncertain, the immune system influences the body by releasing certain substances called antibodies to target tissues.
One of these substances is the ACPA. It disrupts specific cell processes and can fuel a loop of cell damage and autoimmune activity, potentially contributing to RA.
In this write-up, we'll delve into the connection between RA and ACPAs, why ACPAs appear, and how they factor into RA diagnosis.
Does the presence of ACPAs signal rheumatoid arthritis?
Based on a 2021 review of literature, doctors view ACPAs as a specific biological sign, or biomarker, of RA in the blood. However, a positive test for ACPA does not always mean that a person has RA. Levels of rheumatoid factor (RF), another antibody, could also indicate RA.
Medical professionals may take both antibody levels into account when diagnosing RA, as they can signify different aspects of disease progression or outlook. For instance, if an individual tests positive for ACPA and RF, they likely have RA and may experience more severe symptoms. A person who receives a positive ACPA test but not one for RF might have early RA or a risk of developing RA in the future.
But if both ACPA and RF tests come back negative, the individual might still have RA based on other criteria or symptoms, and they may develop ACPAs over time.
If tests are positive for ACPAs and RA, the individual might suffer from a different autoimmune condition, such as systemic lupus erythematosus (SLE) and Sjogren disease. However, this is uncommon.
What distinguishes ACPA-positive from ACPA-negative RA?
An individual develops ACPA-positive RA when they have RA and ACPAs. If they don't have ACPAs, or are ACPA-negative, this might lead to different disease progression.
A 2022 study involving 198 people with RA found that those with ACPA-positive RA had continuously low levels of joint inflammation during periods of remission, but those with ACPA-negative RA responded more to treatment with disease-modifying antirheumatic drugs (DMARDs) in the first year of therapy.
The study also suggests that people with ACPA-negative RA who are in remission have inflammation levels similar to those who do not. However, those with ACPA-positive RA who move into remission exhibit significantly lower inflammation levels from the point of diagnosis onwards.
Some studies concluded that those with ACPA-positive RA demonstrated more severe bone damage than those with ACPA-negative RA. In fact, the scores tracking bone erosion were roughly four times higher in the group with ACPA-positive RA. This erosion most commonly happens in the fifth metatarsophalangeal joint, or little toe joint.
Having ACPA-positive or ACPA-negative RA might impact the influence of environmental risk factors on RA development. For instance, a 2018 study in Sweden discovered that smoking raised a person's risk for RA for both ACPA-positive and ACPA-negative individuals, but it affected ACPA-positive RA more significantly.
What leads to ACPAs?
The immune system creates ACPAs in response to a process called citrullination. Citrullination occurs when an enzyme called peptidyl-arginine deiminase (PAD) swaps arginine, a protein building block (amino acid), into a different amino acid, citrulline.
While this process supports brain development, skin health, and cells dying at their natural point in their life cycle, it occurs too frequently in people with RA. One of the proteins that citrullination affects is collagen, a crucial component of connective tissue, tendons, and ligaments that RA might attack.
Cell damage means that PAD works too hard, leading to excess citrullination. In response, the immune system generates ACPAs to attack the citrullinated proteins. Notably, PAD is found in immune cells, such as neutrophils and monocytes, and ACPAs can reactivate neutrophils, leading to more citrullination.
This feedback loop can raise inflammation and tissue damage in people with RA. Smoking or air pollution could make this worse.
How do doctors test for ACPAs?
Doctors can detect ACPAs using a blood test for CCP antibodies, a type of ACPA. This blood test typically takes no more than 5 minutes.
As these are a type of ACPA, they can help a physician diagnose or rule out RA.
Important: Other conditions can also result in raised CCP antibodies, such as SLE, Sjogren disease, tuberculosis, chronic lung disease, and other health issues. A doctor will take other factors into account when diagnosing RA, including an individual's medical history, physical exam, and the results of other tests."Learn more: How does a doctor diagnose rheumatoid arthritis?
Additional Tests for Diagnosing Rheumatoid Arthritis
Besides focusing on ACPAs, doctors may also test for other antibodies, such as antinuclear antibody (ANA), C-reactive protein (CRP), RF, which demonstrates disease progression, synovial fluid analysis, and X-rays of joints to assess damage.
- In tackling citrullinated proteins, the immune system generates anti-citrullinated protein antibodies (ACPAs), which can help diagnose early-stage rheumatoid arthritis (RA) and predict bone erosion.
- ACPAs are considered a specific biological sign, or biomarker, of RA in the blood, but a positive test does not always mean a person has RA as levels of rheumatoid factor (RF) could also indicate RA.
- Medical professionals might consider both antibody levels when diagnosing RA, as they can signify different aspects of disease progression or outlook, with individuals testing positive for both ACPA and RF likely having RA and possibly experiencing severe symptoms.
- If only a positive ACPA test is received but not one for RF, the individual may have early RA or a risk of developing RA in the future.
- If ACPA and RF tests come back negative, the individual might still have RA based on other criteria or symptoms, and they may develop ACPAs over time.
- A 2022 study found that people with ACPA-positive RA had continuously low levels of joint inflammation during periods of remission, whereas those with ACPA-negative RA responded more to treatment with disease-modifying antirheumatic drugs (DMARDs) in the first year of therapy.
- Inflammation levels can differ between ACPA-positive RA and ACPA-negative RA, with those with ACPA-positive RA displaying significantly lower inflammation levels from the point of diagnosis onwards during remission.
