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How citrullination invaded rheumatoid arthritis research.

van Venrooij WJ, Pruijn GJ - Arthritis Res. Ther. (2014)

Bottom Line: In the first years after the initial publications, the focus was on the antibodies directed to citrullinated proteins.It is now realized that citrullinating enzymes and citrullinated proteins may have important roles in the maintenance of the inflammatory processes in the joints.There is also accumulating evidence for a direct role of citrullination in tissue destruction in the rheumatoid synovium.

View Article: PubMed Central - HTML - PubMed

ABSTRACT
Citrullination and the immune response to citrullinated proteins have been fundamental for the early recognition of rheumatoid arthritis by serological tests and a better understanding of its pathophysiology. In the first years after the initial publications, the focus was on the antibodies directed to citrullinated proteins. It is now realized that citrullinating enzymes and citrullinated proteins may have important roles in the maintenance of the inflammatory processes in the joints. There is also accumulating evidence for a direct role of citrullination in tissue destruction in the rheumatoid synovium. Here we will discuss the development and importance of anti-citrullinated protein antibodies in rheumatoid arthritis as well as recent findings implicating citrullination in the pathophysiology of rheumatoid arthritis.

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Citrullination-related immunity and pathophysiology in rheumatoidarthritis. In genetically susceptible individuals, an environmental factormay initiate a primary inflammation, which can occur in various tissues, andtrigger the immune response to citrullinated proteins (left). The resultinganti-citrullinated protein/peptide antibodies (ACPAs) are distributed through thecirculation and may form immune complexes with citrullinated proteins produced inan inflamed synovium, thereby boosting the inflammatory process. This will beassociated with the infiltration and activation of neutrophils, macrophages, andlymphocytes; cell death; extracellular DNA trap formation; the activation andrelease of peptidylarginine deiminases (PADs); de novo citrullination;and diversification of the ACPA response. Besides the commoninflammation-associated mediators of tissue destruction (not shown), ACPAs andPADs can be directly involved in these processes. HLA, human leukocyteantigen.
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Figure 1: Citrullination-related immunity and pathophysiology in rheumatoidarthritis. In genetically susceptible individuals, an environmental factormay initiate a primary inflammation, which can occur in various tissues, andtrigger the immune response to citrullinated proteins (left). The resultinganti-citrullinated protein/peptide antibodies (ACPAs) are distributed through thecirculation and may form immune complexes with citrullinated proteins produced inan inflamed synovium, thereby boosting the inflammatory process. This will beassociated with the infiltration and activation of neutrophils, macrophages, andlymphocytes; cell death; extracellular DNA trap formation; the activation andrelease of peptidylarginine deiminases (PADs); de novo citrullination;and diversification of the ACPA response. Besides the commoninflammation-associated mediators of tissue destruction (not shown), ACPAs andPADs can be directly involved in these processes. HLA, human leukocyteantigen.

Mentions: 8. ACPAs and citrullinated antigens form immune complexes which stimulate theinflammatory process. Continuous production of such immune complexes ultimately resultsin the chronic inflammation, characteristic for RA (FigureĀ 1).


How citrullination invaded rheumatoid arthritis research.

van Venrooij WJ, Pruijn GJ - Arthritis Res. Ther. (2014)

Citrullination-related immunity and pathophysiology in rheumatoidarthritis. In genetically susceptible individuals, an environmental factormay initiate a primary inflammation, which can occur in various tissues, andtrigger the immune response to citrullinated proteins (left). The resultinganti-citrullinated protein/peptide antibodies (ACPAs) are distributed through thecirculation and may form immune complexes with citrullinated proteins produced inan inflamed synovium, thereby boosting the inflammatory process. This will beassociated with the infiltration and activation of neutrophils, macrophages, andlymphocytes; cell death; extracellular DNA trap formation; the activation andrelease of peptidylarginine deiminases (PADs); de novo citrullination;and diversification of the ACPA response. Besides the commoninflammation-associated mediators of tissue destruction (not shown), ACPAs andPADs can be directly involved in these processes. HLA, human leukocyteantigen.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4061769&req=5

Figure 1: Citrullination-related immunity and pathophysiology in rheumatoidarthritis. In genetically susceptible individuals, an environmental factormay initiate a primary inflammation, which can occur in various tissues, andtrigger the immune response to citrullinated proteins (left). The resultinganti-citrullinated protein/peptide antibodies (ACPAs) are distributed through thecirculation and may form immune complexes with citrullinated proteins produced inan inflamed synovium, thereby boosting the inflammatory process. This will beassociated with the infiltration and activation of neutrophils, macrophages, andlymphocytes; cell death; extracellular DNA trap formation; the activation andrelease of peptidylarginine deiminases (PADs); de novo citrullination;and diversification of the ACPA response. Besides the commoninflammation-associated mediators of tissue destruction (not shown), ACPAs andPADs can be directly involved in these processes. HLA, human leukocyteantigen.
Mentions: 8. ACPAs and citrullinated antigens form immune complexes which stimulate theinflammatory process. Continuous production of such immune complexes ultimately resultsin the chronic inflammation, characteristic for RA (FigureĀ 1).

Bottom Line: In the first years after the initial publications, the focus was on the antibodies directed to citrullinated proteins.It is now realized that citrullinating enzymes and citrullinated proteins may have important roles in the maintenance of the inflammatory processes in the joints.There is also accumulating evidence for a direct role of citrullination in tissue destruction in the rheumatoid synovium.

View Article: PubMed Central - HTML - PubMed

ABSTRACT
Citrullination and the immune response to citrullinated proteins have been fundamental for the early recognition of rheumatoid arthritis by serological tests and a better understanding of its pathophysiology. In the first years after the initial publications, the focus was on the antibodies directed to citrullinated proteins. It is now realized that citrullinating enzymes and citrullinated proteins may have important roles in the maintenance of the inflammatory processes in the joints. There is also accumulating evidence for a direct role of citrullination in tissue destruction in the rheumatoid synovium. Here we will discuss the development and importance of anti-citrullinated protein antibodies in rheumatoid arthritis as well as recent findings implicating citrullination in the pathophysiology of rheumatoid arthritis.

Show MeSH
Related in: MedlinePlus