Rheumatoid arthritis and the ACPA connection: Key insights explained
Let's Get Down to Business: Breaking Down ACPAs and Their Impact on Rheumatoid Arthritis
ACPA 101: Anti-citrullinated protein antibodies, or ACPAs, are a type of autoantibody that targets citrullinated proteins. They're like little soldiers dispatched by your immune system to attack proteins that have gone through a process called citrullination. ACPAs play a crucial role in the early diagnosis and bone erosion prediction of rheumatoid arthritis (RA) [1].
Diagnosis and Prediction: Doctors consider ACPAs a specific biological sign, or biomarker, of RA. However, a positive test for ACPA isn't always a confirmatory RA diagnosis. The presence of rheumatoid factor (RF), another antibody, could also be indicative of RA [2]. Doctors will typically evaluate levels of both antibodies when diagnosing RA, as they provide insights into the progression and prognosis of the disease. For example, an individual with positive ACPA and RF tests may experience more aggressive RA symptoms [2]. On the other hand, a positive ACPA test without an RF test could indicate early RA or a future risk of developing RA.
It's essential to note that negative ACPA and RF tests don't necessarily rule out RA. The individual might still have RA based on other criteria or symptoms, and they may develop ACPAs over time [2]. In rare cases, ACPA-positive tests could indicate other autoimmune conditions, such as systemic lupus erythematosus (SLE) or Sjogren's disease [2].
ACPA-positive vs ACPA-negative: Individuals with ACPA-positive RA are more likely to have continuously low levels of joint inflammation during periods of remission compared to those with ACPA-negative RA. This group tends to respond less effectively to the first year of disease-modifying antirheumatic drug (DMARD) therapy [3]. People with ACPA-negative RA in remission have similar inflammation levels to those without RA, whereas ACPA-positive RA patients in remission have substantially lower inflammation levels from the point of diagnosis onward [3]. ACPA-positive RA may also lead to more severe bone damage, with erosion scores up to 4.4 times higher compared to ACPA-negative RA [3]. This bone erosion often occurs in the fifth metatarsophalangeal joint, or little toe joint.
Environmental factors, like smoking, may impact the development of RA differently depending on ACPA status. For instance, smoking increases the risk of RA for both ACPA-positive and ACPA-negative individuals, but it has a more significant influence on ACPA-positive RA [4].
Where Do ACPAs Come From: The immune system produces ACPAs in response to a process called citrullination [5]. Citrullination takes place when an enzyme called peptidyl-arginine deiminase (PAD) alters an amino acid called arginine into a different amino acid, citrulline. While citrullination is a natural process that supports brain development, skin health, and cell death, overactivity in those with RA leads to excessive citrullination. As a result, the immune system counteracts with ACPAs that attack the citrullinated proteins [5]. Interestingly, PAD can be found in immune cells like neutrophils and monocytes, and ACPAs can reactivate these cells, creating an accumulating feedback loop of inflammation and tissue damage in RA individuals [5]. Smoking or air pollution can worsen this situation.
Testing for ACPAs: A simple blood test for CCP antibodies — a type of ACPA — can help diagnose or rule out RA. These tests usually take just a few minutes [2]. Other conditions, like SLE, Sjogren's disease, tuberculosis, and chronic lung disease, can also trigger raised CCP antibodies [6]. Therefore, doctors will consider other factors, like an individual's medical history, a physical exam, and the results of other tests, when diagnosing RA.
What Else Doctors Test For: RA can be a tricky condition, and doctors may run additional tests to confirm a diagnosis. These tests involve other antibodies like antinuclear antibodies, C-reactive protein, RF, and synovial fluid analysis [6]. X-rays of the joints can help assess damage as well [6].
The Nitty-Gritty: ACPAs vs Anti-CCP Antibodies: Anti-cyclic citrullinated peptide (anti-CCP) antibodies are a subset of ACPAs. They react to CCPs such as fibrinogen or myelin basic protein, but they respond differently to each. ACPAs can react to multiple proteins, not just CCPs. Both anti-CCP and ACPAs are highly specific for RA and valuable in both diagnosis and prognosis [7].
In essence, ACPAs play a significant role in the diagnosis and progression of RA. They can help identify individuals at risk of severe joint damage and provide essential insights into the severity of the disease. While rheumatoid factor (RF) is also used in diagnosis, ACPAs are more specific and predictive of disease severity.
- Doctors consider Anti-citrullinated protein antibodies (ACPAs) a specific biological sign of rheumatoid arthritis (RA), aiding in the early diagnosis and prediction of bone erosion.
- A positive ACPA test isn't always a confirmatory RA diagnosis, and doctors may evaluate levels of both ACPAs and rheumatoid factor (RF) when diagnosing RA.
- Individuals with ACPA-positive RA have more continuous low levels of joint inflammation and are less responsive to the first year of disease-modifying antirheumatic drug (DMARD) therapy compared to ACPA-negative RA.
- ACPA-positive RA may lead to more severe bone damage, with erosion scores up to 4.4 times higher compared to ACPA-negative RA.
- Environmental factors like smoking can impact the development of RA differently depending on ACPA status, with smoking having a more significant influence on ACPA-positive RA.
- ACPAs are produced in response to citrullination, a natural process that involves an enzyme called peptidyl-arginine deiminase (PAD) altering arginine to citrulline.
- A simple blood test for CCP antibodies (a type of ACPA) can help diagnose or rule out RA, but doctors may also test for other factors like antinuclear antibodies, C-reactive protein, RF, synovial fluid analysis, and X-rays of the joints to confirm a diagnosis of RA.
