Rheumatoid Arthritis and the ACPA Connection: Essential Facts to Understand
The immune system generates antibodies known as anti-citrullinated protein antibodies (ACPAs) to fight citrullinated proteins. These ACPAs can aid doctors in detecting early signs of rheumatoid arthritis (RA) and predicting whether it's likely to cause joint bone erosion.
RA is an autoimmune illness, meaning the immune system attacks the body's own tissues unintentionally, leading to pain, stiffness, and inflammation in the joints. While the root causes of RA remain elusive, the immune system harms the body through the release of specific chemicals called antibodies that target specific tissues.
Among these antibodies is the ACPA. It disrupts cell processes and can trigger a cycle of cell damage and autoimmune activity that might contribute to the onset and progression of RA.
Let's dive into the connection between RA and ACPAs, why ACPAs come about, and how they factor into RA diagnosis.
Do ACPAs Point to Rheumatoid Arthritis?
A 2021 analysis of numerous literature sources reveals that ACPAs serve as a specific biological marker, or biomarker, of RA in the blood for doctors.
That said, a positive ACPA test doesn't automatically mean an individual has RA. Levels of rheumatoid factor (RF), another antibody, might also indicate RA.
Medical professionals may consider both antibody levels when diagnosing RA, as they provide insights into the progression or outlook of the disease. For instance, an individual who tests positive for both ACPA and RF might have more severe RA symptoms. A person with a positive ACPA test but negative RF result may have early-stage RA or an increased risk of developing RA in the future.
However, if neither ACPA nor RF tests come back positive, the individual might still have RA based on other criteria or physical symptoms, and they could still develop ACPAs over time.
If tests indicate the presence of ACPAs and RA, the individual may suffer from a different autoimmune condition, such as systemic lupus erythematosus (SLE) or Sjögren's disease. This is rare.
ACPA-Positive vs. ACPA-Negative RA
ACPA-positive RA develops when someone with RA has ACPAs. If they do not have ACPAs, or are ACPA-negative, this might lead to different disease progression.
A 2022 study involving 198 individuals with RA found that those with ACPA-positive RA had persistently low levels of joint inflammation during remission. However, those with ACPA-negative RA were more responsive to treatment with disease-modifying antirheumatic drugs (DMARDs) in the first year of therapy.
The study also suggested that people with ACPA-negative RA who are in remission have inflammation levels similar to those who do not suffer from RA. In contrast, those with ACPA-positive RA who move into remission have significantly lower inflammation levels from the start.
Some research involving 108 individuals with RA found that those with ACPA-positive RA exhibited more severe bone damage than people with ACPA-negative RA. The scores tracking bone erosion were 3.7 to 4.4 times higher in the group with ACPA-positive RA, often occurring in the fifth metatarsophalangeal joint, or little toe joint.
Having ACPA-positive or ACPA-negative RA might also influence the impact of environmental risk factors on RA development. For example, a 2018 study in Sweden revealed that smoking increased a person's risk of RA for both ACPA-positive and ACPA-negative individuals. However, smoking had a more significant effect on ACPA-positive RA.
What Causes ACPAs?
The immune system produces ACPAs as a response to citrullination, which is a process that transforms an essential protein building block called arginine into citrulline. This process occurs in people with RA at an elevated rate. One of the proteins that citrullination affects is collagen, a crucial component of connective tissue, tendons, and ligaments that RA may damage.
Cell damage might cause PAD to work too hard, leading to excess citrullination. In response, the immune system generates ACPAs that attack the citrullinated proteins. However, PAD resides in immune cells like neutrophils and monocytes, and ACPAs may reactivate neutrophils, causing further citrullination.
This feedback loop can boost inflammation and tissue damage in people with RA. Factors like smoking or air pollution might exacerbate this.
Testing for ACPAs
Doctors can detect ACPAs using a blood test for CCP antibodies, a type of ACPA. This blood test usually takes no more than 5 minutes. As these are a type of ACPA, they can help a physician diagnose or rule out RA.
However, other conditions can also result in elevated CCP antibody levels. These include SLE, Sjögren's disease, tuberculosis, and chronic lung disease. A doctor will consider other factors when diagnosing RA, including an individual's medical history, a physical exam, and the results of other tests.
"Learn more:How does a doctor diagnose rheumatoid arthritis?## Additional Tests for Diagnosing RA
RA is complex, and doctors often test for other antibodies to confirm a diagnosis. These include antinuclear antibodies, C-reactive protein, RF, synovial fluid analysis, and X-rays of the joints to assess damage.
ACPA vs. CCP Antibodies
According to a 2022 review, anti-cyclic citrullinated peptides (anti-CCP) antibodies are a type of ACPA. Anti-CCP antibodies react to CCPs such as fibrinogen or myelin basic protein but respond differently to each. In contrast, ACPAs can react to more than just CCPs.
- A 2021 analysis of various literature sources indicates that ACPAs, or anti-citrullinated protein antibodies, serve as a specific biomarker, or biomarker, of rheumatoid arthritis (RA) in the blood for doctors.
- A positive ACPA test might suggest an increased risk of developing RA or early-stage RA, but a positive test result alone does not confirm an RA diagnosis.
- Medical professionals may consider both ACPA and rheumatoid factor (RF) levels when diagnosing RA, as these antibody levels can provide insights into the progression or outlook of the disease.
- The presence of ACPAs and RA might indicate a different autoimmune condition, such as systemic lupus erythematosus (SLE) or Sjögren's disease, which is rare.
- ACPAs are generated by the immune system in response to citrullination, a process that affects proteins like collagen, contributing to the onset and progression of rheumatoid arthritis and aiding doctors in detecting early signs of the disease.
