Filaggrin is a protein found within the human body, playing a specific role in certain tissues. The immune system typically produces antibodies to identify and neutralize foreign substances. However, sometimes the immune system mistakenly creates antibodies that target the body’s own healthy proteins. These self-targeting antibodies are called autoantibodies. An antibody against filaggrin is an example of such an autoantibody.
Understanding Filaggrin: The Protein Target
Filaggrin is a structural protein found in the outermost layer of the skin, the stratum corneum. It is initially produced as a large precursor molecule called profilaggrin. During skin maturation, profilaggrin undergoes processing to yield individual filaggrin units. These units then bind to and compact keratin filaments, helping to organize them into a dense, protective barrier.
This aggregation of keratin filaments by filaggrin is important for maintaining the skin’s barrier function. A healthy skin barrier prevents excessive water loss and blocks the entry of external allergens, irritants, and pathogens. Filaggrin also breaks down into smaller, water-attracting molecules that contribute to the skin’s natural moisturizing factor, helping to keep the skin hydrated. A deficiency in filaggrin can lead to a compromised skin barrier, making the skin more susceptible to environmental factors.
How Filaggrin Antibodies Form
The formation of antibodies against filaggrin involves the immune system misidentifying its own proteins as foreign. This often begins with a chemical change called citrullination. In this process, the amino acid arginine is converted into citrulline by enzymes called peptidylarginine deiminases (PADs). This alteration changes the protein’s shape and charge, potentially making it appear unfamiliar to the immune system.
When filaggrin, or other proteins, undergo citrullination, the immune system can mistakenly recognize these modified “self” proteins as threats. This leads to the production of autoantibodies that specifically target the citrullinated forms. These autoantibodies are known as anti-citrullinated protein antibodies (ACPAs). An exaggerated or dysregulated citrullination can fuel the generation of these autoantibodies.
Filaggrin Antibodies and Their Link to Autoimmune Disease
Filaggrin antibodies are significant due to their strong association with Rheumatoid Arthritis (RA), a chronic autoimmune condition affecting joints. Anti-citrullinated protein antibodies (ACPAs), which target modified proteins like filaggrin, are recognized as a specific marker for RA. The presence of ACPAs in the blood can precede the onset of RA symptoms by several years.
ACPAs are detected in approximately two-thirds of individuals with RA and show high diagnostic specificity. Their presence is consistently linked to a more severe disease course in RA, including greater structural damage to joints and a poorer response to certain therapies. These antibodies can contribute to inflammation and bone erosion. While primarily associated with RA, ACPAs have also been detected in a smaller percentage of individuals with other autoimmune disorders, such as Sjögren’s syndrome or systemic lupus erythematosus.
Detecting and Interpreting Filaggrin Antibody Levels
The detection of filaggrin antibodies typically occurs through a blood test, often as part of an anti-citrullinated peptide antibody (ACPA) panel. The most common method used is an enzyme-linked immunosorbent assay (ELISA), which can identify antibodies that react with citrullinated peptides. This test helps in diagnosing or ruling out rheumatoid arthritis, especially when combined with other clinical evaluations.
A positive result for filaggrin antibodies, often reported as positive ACPA, indicates the presence of these autoantibodies in the blood. If a person has symptoms of rheumatoid arthritis and a positive ACPA test, it strongly suggests they have RA or are likely to develop it. A negative result means these antibodies were not detected, making RA less likely, though it does not entirely rule out the disease. Healthcare professionals interpret these results alongside a person’s symptoms, medical history, and other laboratory tests to reach a comprehensive diagnosis.