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    Peptidyl Arginine Deiminase (PAD)
    • Immunology
    • BTK
    • CTLA-4
    • IL-13
    • MK2
    • PAD
    • S1P-1R
    • TLR 7/8
    • TYK2

    PAD

    An essential step in the formation of ACPA autoantibodies is the citrullination of self-protein by peptidyl arginine deiminase (PAD), a family of enzymes that modify proteins by converting arginine to citrulline and conferring antigenic potential.1-3

    • In susceptible individuals, tolerance to citrullinated self-proteins breaks down and these PAD-modified self-proteins become self-antigens, driving T-cell activation, differentiation and consequent inflammation.1,4
    • T-cells in turn promote B-cell maturation and activation of B cells, with ultimate production of autoantibodies to citrullinated self-proteins, which may appear many years prior to onset of disease symptoms.1,4,5
    • Circulating ACPA autoantibodies that enter the joint as well as those generated within the joint induce local inflammation through the formation of immune complexes with PAD-citrullinated proteins.4,6
    • PAD-induced anti-citrullinated protein autoantibodies (ACPAs) have been associated with more aggressive autoimmune disease with a poorer prognosis.3,5

    Peptidyl Arginine Deiminase (PAD)

    References

    1. Klareskog L, Rönnelid J, Lundberg K, et al. Ann Rev Immunol. 2008;26:651-75.
    2. Gudmann NS, Hansen NUB, Jensen ACB, et al. Autoimmunity. 2015;48(2):73-79.
    3. Mowen KA, David M. Nature Immunol. 2014;15(6):512-520.
    4. Catrina AI, Ytterberg J, Reynisdottir G, et al. Nature Reviews/Rheum. 2014;10:645-653.
    5. loan-Facsinay A, el-Bannoudi H, Scherer HU, et al. Ann Rheum Dis. 2011;70:188-193.
    6. Spengler J, Lugonja B, Ytterberg AJ, et al. Arthritis & Rheumatol. 2015;67(12):3135-3145.
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