Erosive rheumatoid arthritis is associated with antibodies that activate PAD4 by increasing calcium sensitivity

Science Translational Medicine

Volumn 5, Issue 186, 2013, Pages

  Darrah, Erika ^a   Giles, Jon T ^b   Ols, Michelle L ^a,c   Bull, Herbert G ^d   Andrade, Felipe ^a   Rosen, Antony ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b College of Physicians and Surgeons ^*  (United States)

^c BIOGEN   (United States)

^d NONE

Author keywords

[No Author keywords available]

Indexed keywords

AUTOANTIBODY; CALCIUM ION; CYCLIC CITRULLINATED PEPTIDE ANTIBODY; DISEASE MODIFYING ANTIRHEUMATIC DRUG; GLUCOCORTICOID; PEPTIDYLARGININE DEIMINASE 3; PEPTIDYLARGININE DEIMINASE 3 ANTIBODY; PEPTIDYLARGININE DEIMINASE 4; PEPTIDYLARGININE DEIMINASE 4 ANTIBODY; PROTEIN ARGININE DEIMINASE; UNCLASSIFIED DRUG;

ADULT; ARTICLE; BONE EROSION; CALCIUM BINDING; CLINICAL ARTICLE; CONTROLLED STUDY; CROSS REACTION; DISEASE SEVERITY; ENZYME ACTIVITY; FEMALE; HUMAN; JOINT SPACE NARROWING; MALE; MUSCULOSKELETAL SYSTEM PARAMETERS; PRIORITY JOURNAL; RHEUMATOID ARTHRITIS;

ANTIBODIES; ARTHRITIS, RHEUMATOID; ASPARTIC ACID; AUTOANTIBODIES; CALCIUM; CROSS REACTIONS; DISEASE PROGRESSION; ENZYME ACTIVATION; FEMALE; HISTONES; HUMANS; HYDROLASES; JOINTS; KINETICS; MALE; MIDDLE AGED; SUBSTRATE SPECIFICITY;

EID: 84878321478     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3005370     Document Type: Article

References (30)

1. W. P. Arend, G. S. Firestein, Pre-rheumatoid arthritis: Predisposition and transition to clinical synovitis. Nat. Rev. Rheumatol. 8, 573-586 (2012).
2. E. R. Vossenaar, A. J. Zendman, W. J. van Venrooij, G. J. Pruijn, PAD, a growing family of citrullinating enzymes: Genes, features and involvement in disease. Bioessays 25, 1106-1118 (2003).
3. A. Willemze, L. A. Trouw, R. E. Toes, T. W. Huizinga, The influence of ACPA status and characteristics on the course of RA. Nat. Rev. Rheumatol. 8, 144-152 (2012).
4. K. Nakashima, T. Hagiwara, M. Yamada, Nuclear localization of peptidylarginine deiminase V and histone deimination in granulocytes. J. Biol. Chem. 277, 49562-49568 (2002).
5. C. Foulquier, M. Sebbag, C. Clavel, S. Chapuy-Regaud, R. Al Badine, M. C. Méchin, C. Vincent, R. Nachat, M. Yamada, H. Takahara, M. Simon, M. Guerrin, G. Serre, Peptidyl arginine deiminase type 2 (PAD-2) and PAD-4 but not PAD-1, PAD-3, and PAD-6 are expressed in rheumatoid arthritis synovium in close association with tissue inflammation. Arthritis Rheum. 56, 3541-3553 (2007).
6. P. L. Kearney, M. Bhatia, N. G. Jones, L. Yuan, M. C. Glascock, K. L. Catchings, M. Yamada, P. R. Thompson, Kinetic characterization of protein arginine deiminase 4: A transcriptional corepressor implicated in the onset and progression of rheumatoid arthritis. Biochemistry 44, 10570-10582 (2005).
7. I. Auger, M. Martin, N. Balandraud, J. Roudier, Rheumatoid arthritis-specific autoantibodies to peptidyl arginine deiminase type 4 inhibit citrullination of fibrinogen. Arthritis Rheum. 62, 126-131 (2010).
8. S. Pollmann, M. Stensland, E. H. Halvorsen, L. M. Sollid, T. K. Kvien, B. Fleckenstein, O. Molberg, Anti-PAD4 autoantibodies in rheumatoid arthritis: Levels in serum over time and impact on PAD4 activity as measured with a small synthetic substrate. Rheumatol. Int. 32, 1271-1276 (2012).
9. W. G. Robertson, R. W. Marshall, Ionized calcium in body fluids. Crit. Rev. Clin. Lab. Sci. 15, 85-125 (1981).
10. H. R. Hill, N. H. Augustine, H. S. Jaffe, Human recombinant interferon γ enhances neonatal polymorphonuclear leukocyte activation and movement, and increases free intracellular calcium. J. Exp. Med. 173, 767-770 (1991).
11. K. Wong, L. Kwan-Yeung, Sphingosine mobilizes intracellular calcium in human neutrophils. Cell Calcium 14, 493-505 (1993).
12. E. H. Halvorsen, S. Pollmann, I. M. Gilboe, D. van der Heijde, R. Landewé, S. Ødegård, T. K. Kvien, Ø. Molberg, Serum IgG antibodies to peptidylarginine deiminase 4 in rheumatoid arthritis and associations with disease severity. Ann. Rheum. Dis. 67, 414-417 (2008).
13. M. L. Harris, E. Darrah, G. K. Lam, S. J. Bartlett, J. T. Giles, A. V. Grant, P. Gao, W. W. Scott Jr., H. El-Gabalawy, L. Casciola-Rosen, K. C. Barnes, J. M. Bathon, A. Rosen, Association of autoimmunity to peptidyl arginine deiminase type 4 with genotype and disease severity in rheumatoid arthritis. Arthritis Rheum. 58, 1958-1967 (2008).
14. J. Zhao, Y. Zhao, J. He, R. Jia, Z. Li, Prevalence and significance of anti-peptidylarginine deiminase 4 antibodies in rheumatoid arthritis. J. Rheumatol. 35, 969-974 (2008).
15. J. R. Kolfenbach, K. D. Deane, L. A. Derber, C. I. O'Donnell, W. R. Gilliland, J. D. Edison, A. Rosen, E. Darrah, J. M. Norris, V. M. Holers, Autoimmunity to peptidyl arginine deiminase type 4 precedes clinical onset of rheumatoid arthritis. Arthritis Rheum. 62, 2633-2639 (2010).
16. E. H. Halvorsen, E. A. Haavardsholm, S. Pollmann, A. Boonen, D. van der Heijde, T. K. Kvien, Ø. Molberg, Serum IgG antibodies to peptidylarginine deiminase 4 predict radiographic progression in patients with rheumatoid arthritis treated with tumour necrosis factor-α blocking agents. Ann. Rheum. Dis. 68, 249-252 (2009).
17. E. Darrah, A. Rosen, J. T. Giles, F. Andrade, Peptidylarginine deiminase 2, 3 and 4 have distinct specificities against cellular substrates: Novel insights into autoantigen selection in rheumatoid arthritis. Ann. Rheum. Dis. 71, 92-98 (2012).
18. D. van der Heijde, How to read radiographs according to the Sharp/van der Heijde method. J. Rheumatol. 26, 743-745 (1999).
19. 2+-induced activation of human PAD4. Nat. Struct. Mol. Biol. 11, 777-783 (2004).
20. N. A. Thornberry, T. A. Rano, E. P. Peterson, D. M. Rasper, T. Timkey, M. Garcia-Calvo, V. M. Houtzager, P. A. Nordstrom, S. Roy, J. P. Vaillancourt, K. T. Chapman, D. W. Nicholson, A combinatorial approach defines specificities of members of the caspase family and granzyme B. Functional relationships established for key mediators of apoptosis. J. Biol. Chem. 272, 17907-17911 (1997).
21. L. Casciola-Rosen, F. Andrade, D. Ulanet, W. B. Wong, A. Rosen, Cleavage by granzyme B is strongly predictive of autoantigen status: Implications for initiation of autoimmunity. J. Exp. Med. 190, 815-826 (1999).
22. D. B. Ulanet, M. Torbenson, C. V. Dang, L. Casciola-Rosen, A. Rosen, Unique conformation of cancer autoantigen B23 in hepatoma: A mechanism for specificity in the autoimmune response. Proc. Natl. Acad. Sci. U.S.A. 100, 12361-12366 (2003).
23. A. Kinloch, K. Lundberg, R. Wait, N. Wegner, N. H. Lim, A. J. Zendman, T. Saxne, V. Malmström, P. J. Venables, Synovial fluid is a site of citrullination of autoantigens in inflammatory arthritis. Arthritis Rheum. 58, 2287-2295 (2008).
24. I. Neeli, S. N. Khan, M. Radic, Histone deimination as a response to inflammatory stimuli in neutrophils. J. Immunol. 180, 1895-1902 (2008).
25. A. Rosen, L. Casciola-Rosen, Autoantigens in systemic autoimmunity: Critical partner in pathogenesis. J. Intern. Med. 265, 625-631 (2009).
26. B. Knuckley, C. P. Causey, J. E. Jones, M. Bhatia, C. J. Dreyton, T. C. Osborne, H. Takahara, P. R. Thompson, Substrate specificity and kinetic studies of PADs 1, 3, and 4 identify potent and selective inhibitors of protein arginine deiminase 3. Biochemistry 49, 4852-4863 (2010).
27. V. C. Willis, A. M. Gizinski, N. K. Banda, C. P. Causey, B. Knuckley, K. N. Cordova, Y. Luo, B. Levitt, M. Glogowska, P. Chandra, L. Kulik, W. H. Robinson, W. P. Arend, P. R. Thompson, V. M. Holers, N-α-benzoyl-N5-(2- chloro-1-iminoethyl)-L-ornithine amide, a protein arginine deiminase inhibitor, reduces the severity of murine collagen-induced arthritis. J. Immunol. 186, 4396-4404 (2011).
28. F. Andrade, E. Darrah, M. Gucek, R. N. Cole, A. Rosen, X. Zhu, Autocitrullination of human peptidyl arginine deiminase type 4 regulates protein citrullination during cell activation. Arthritis Rheum. 62, 1630-1640 (2010).
29. I. H. Segel, Enzyme Kinetics (John Wiley and Sons, New York, 1975), chap. 360-361.
30. W. DeLano, The PyMOL Molecular Graphics System (DeLano Scientific, Palo Alto, CA, 2002); http://www.pymol.org.