What is the function of citrullination?

Citrullination has an important role in the normal function of the immune system, skin keratinization, the insulation of neurons and the plasticity of the central nervous system including its essential role in gene regulation.

How does citrullination cause rheumatoid arthritis?

Citrullination, the post-translational conversion of arginine to citrulline residues by peptidylarginine deiminase enzymes (PADs), is thought to be an essential contributor to the rheumatoid arthritis (RA) disease pathogenesis.

What causes citrullination?

Histone citrullination occurs by enzymatic conversion of arginine residue to citrulline. This leads to chromatin relaxation and enables activation of transcription.

What is protein citrullination?

Citrullination or deimination is the conversion of the amino acid arginine in a protein into the amino acid citrulline. The immune system can attack citrullinated proteins, leading to autoimmune diseases such as rheumatoid arthritis (RA) and multiple sclerosis (MS).

Is citrullination reversible?

In contrast to many other posttranslational modification (PTM), citrullination appears to be an irreversible process.

Is citrullination a normal process?

The irreversible citrullination reaction is not limited to a specific protein, cell, or tissue. It can target a wide range of proteins in the cell membrane, cytoplasm, nucleus, and mitochondria. Citrullination is a normal reaction during cell death.

Is anti-CCP and ACPA?

Newer assays detect non-cyclic citrullinated peptides (41); the term anti-citrullinated peptide antibody (ACPA) has thus replaced anti-cyclic citrullinated peptide (anti-CCP) antibody. Citrullinated vimentin is present in synovial fluid.

What is ACPA positive rheumatoid arthritis?

Rheumatoid arthritis (RA) is associated with HLA-DRB1 shared epitope (HLA-DRB1SE) and anti-citrullinated protein autoantibodies (ACPAs). ACPAs precedes the onset of clinical and subclinical RA.

Which antibodies are most diagnostic for rheumatoid arthritis?

With their excellent specificity, anti‐CCP antibodies can be useful in establishing the diagnosis of RA, but IgM RF is a better predictor of disease severity. Rheumatoid arthritis, Anti‐cyclic citrullinated peptide antibodies, Anti‐keratin antibodies, IgM rheumatoid factor.

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What is the function of Citrullination?

What is TNC in synovial fluid?

Tenascin-C (TNC) is a large multimodular glycoprotein of the extracellular matrix that consists of four distinct domains. Emerging evidence suggests that TNC may be involved in the pathogenesis of osteoarthritis (OA) and rheumatoid arthritis (RA).

Is rheumatoid Arthritis a disease?

Rheumatoid arthritis, or RA, is an autoimmune and inflammatory disease, which means that your immune system attacks healthy cells in your body by mistake, causing inflammation (painful swelling) in the affected parts of the body.

What does rheumatoid Arthritis affect?

The joints most often affected by RA are in the hands, wrists, feet, ankles, knees, shoulders, and elbows. Symptoms may include joint pain, stiffness, and swelling; decreased and painful movement; bumps over small joints; and fatigue or fever.

How does citrullination cause RA?

ACPAs and citrullinated antigens form immune complexes which stimulate the inflammatory process. Continuous production of such immune complexes ultimately results in the chronic inflammation, characteristic for RA (Figure 1).

What is citrullination in rheumatoid arthritis?

What does high WBC in synovial fluid mean?

The synovial fluid may be cloudy or thick. A high white blood cell count could mean you have an infection or another medical condition. A high uric acid level and crystals could signal gout.

What is the function of articular cartilage?

Articular cartilage is the smooth, white tissue that covers the ends of bones where they come together to form joints. Healthy cartilage in our joints makes it easier to move. It allows the bones to glide over each other with very little friction.

Where does citrullination happen?

This form of post-translational protein modification creates novel epitopes on common proteins, providing ‘neoantigens’ that are now known to be important in autoimmune disease. Citrullination can occur outside of the cell, in the cytoplasm, and in the nucleus.

Is citrullinated tenascin-C a target for autoantibodies in rheumatoid arthritis?

Schwenzer, A. et al. Identification of an immunodominant peptide from citrullinated tenascin-C as a major target for autoantibodies in rheumatoid arthritis. Ann. Rheum. Dis. 75, 1876–1883 (2016).

Which tenascin C peptides give the most robust T cell responses?

One of the Tenascin C peptides, cit-TNC22, gave the most robust T cell responses including biased TCR gene usage patterns. The shared TCR-beta chain signature among the cit-TNC22-specific TCRs was evident in blood and synovial fluid of different patients.

What is tenascin-C?

Tenascin-C is a large, multimodular, extracellular matrix glycoprotein that exhibits a very restricted pattern of expression but an enormously diverse range of functions.

Is tenascin-C a toll-like receptor 4 activator?

Midwood, K. et al. Tenascin-C is an endogenous activator of Toll-like receptor 4 that is essential for maintaining inflammation in arthritic joint disease. Nat. Med. 15, 774–780 (2009).

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