Rheumatoid Arthritis and the ACPA Connection: Essential Facts Explained
Let's Talk Rheumatoid Arthritis (RA): An In-depth Look at ACPAs
Anti-citrullinated protein antibodies (ACPAs) are proteins that the immune system produces to target proteins after a process called citrullination. These antibodies can help doctors diagnose early RA and predict the severity of the disease.
RA, an autoimmune disorder, is characterized by the immune system attacking the body's own tissues, resulting in pain, stiffness, and swelling in the joints. ACPAs, like other antibodies, disrupt cell processes, contributing to a cycle of cell damage and autoimmune activity that may aggravate RA.
While the causes of RA remain unclear, the immune system affects the body by releasing certain chemicals, including ACPAs.
ACPAs: A Biomarker for RA Diagnosis
According to a 2021 literature review, ACPAs serve as a specific biological sign or biomarker in the blood for RA. However, a positive ACPA test does not always indicate an RA diagnosis. Levels of rheumatoid factor (RF), another antibody, could also point towards RA. Doctors may consider both antibodies when diagnosing RA, as they offer different insights into the disease's progression or outlook.
For example, a person with a positive ACPA and RF test may have more aggressive RA symptoms. A person with a positive ACPA test but negative RF could have early RA or a higher risk of developing RA in the future. On the other hand, if both tests are negative, the individual might still have RA based on other criteria or symptoms.
ACPA-Positive vs ACPA-Negative RA
RA can be either ACPA-positive or ACPA-negative, which can lead to different disease progressions.
A 2022 study involving 198 people with RA found that those with ACPA-positive RA had lower levels of joint inflammation during periods of remission compared to those with ACPA-negative RA. This group also responded less to treatment with disease-modifying antirheumatic drugs (DMARDs) in the first year of therapy.
The study suggests that ACPA-negative RA patients in remission have similar inflammation levels to those who do not have RA. In contrast, ACPA-positive RA patients who achieve remission have significantly lower inflammation levels from the point of diagnosis onward.
ACPA-positive RA patients also tend to show more severe bone damage than ACPA-negative patients, with higher scores tracking bone erosion[4]. This erosion often occurs in the fifth metatarsophalangeal joint, or little toe joint.
What Causes ACPAs?
The immune system produces ACPAs in response to a process called citrullination, which occurs when an enzyme called peptidyl-arginine deiminase (PAD) converts arginine, a protein building block called an amino acid, into citrulline. While citrullination usually supports brain development, skin health, and cell death at the natural point in their life cycle, it happens too much in people with RA, particularly in the connective tissue, tendons, and ligaments that RA may affect[5].
This excess citrullination leads to cell damage, which causes PAD to work harder and produce more ACPAs, creating an inflammatory feedback loop that contributes to tissue damage in people with RA. Smoking or air pollution may exacerbate this process[5].
Testing for ACPAs
Doctors can identify ACPAs using a simple blood test for cyclic citrullinated peptides (anti-CCP) antibodies, a type of ACPA. Other conditions such as SLE, Sjogren's disease, tuberculosis, and chronic lung disease can also lead to raised CCP antibodies[6]. A doctor will consider other factors when diagnosing RA, including a person's medical history, physical exam, and results from other tests.
Other Tests for RA Diagnosis
Apart from ACPA tests, doctors may also test for other antibodies like antinuclear antibodies, C-reactive protein, RF, and examine synovial fluid analysis to confirm a RA diagnosis. X-rays of the joints may be requested to assess damage[6].
ACPAs vs CCP Antibodies
Anti-CCP antibodies are a type of ACPA. They react to cyclic citrullinated peptides such as fibrinogen or myelin basic protein differently. ACPAs can react to more than just CCPs[7].
[1] https://pubmed.ncbi.nlm.nih.gov/34595050/[2] https://pubmed.ncbi.nlm.nih.gov/22726908/[3] https://journals.sagepub.com/doi/10.1177/0026744517704640[4] https://pubmed.ncbi.nlm.nih.gov/34028543/[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8491107/[6] https://www.mayoclinic.org/tests-procedures/ccp-blood-test/about/pac-20394934[7] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9320607/
- Rheumatoid arthritis (RA), a chronic disease, is characterized by the immune system targeting its own tissues, causing pain, stiffness, and swelling in the joints.
- Anti-citrullinated protein antibodies (ACPAs) are proteins produced by the immune system to target proteins after citrullination, aiding in RA diagnosis and predicting its severity.
- ACPAs serve as a biomarker for RA, but a positive ACPA test does not always indicate an RA diagnosis, as levels of rheumatoid factor (RF) could also point towards RA.
- RA can be either ACPA-positive or ACPA-negative, leading to different disease progressions and responses to therapies and treatments.
- A 2022 study found that ACPA-positive RA patients during remission had lower levels of joint inflammation compared to ACPA-negative patients and were less responsive to disease-modifying antirheumatic drugs (DMARDs).
- ACPA-positive RA patients tend to show more severe bone damage, with higher scores tracking bone erosion in the fifth metatarsophalangeal joint.
- Doctors can identify ACPAs using a simple blood test for cyclic citrullinated peptides (anti-CCP) antibodies, but other medical conditions like SLE, Sjogren's disease, tuberculosis, and chronic lung disease can also lead to raised CCP antibodies.
