Abstract
Type 1 diabetes (T1D) is an immune-mediated disease in which the insulin-producing beta cells are selectively targeted for destruction. An important component of this immune destruction is mediated through CD4+ and CD8+ T cells that recognize epitopes derived from beta cell proteins. This chapter addresses the increasingly appreciated role that deimination of self-proteins plays in T1D, based on observations in human subjects and insights gained through the NOD model. After addressing the general phenomenon of determinant spreading we present evidence supporting the enhanced presentation of deiminated peptides by T1D susceptible HLA and the in vivo conversion of arginine to citrulline both in model antigens and beta cell associated proteins. Furthermore, we present evidence that enzymatic deimination of arginine to citrulline is promoted by beta cell stress and that peptides derived from established beta cell antigens are preferentially recognized by T cells in their deiminated form. Finally, we discuss prospects for diagnostic detection of anti-citrulline responses in T1D.
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Almeida, M. H., Dantas, J. R., Barone, B., Serfaty, F. M., Kupfer, R., Albernaz, M., Bencke, M. R., Zajdenverg, L., Rodacki, M., & Oliveira, J. E. (2013). Residual C-peptide in patients with type 1 diabetes and multiethnic backgrounds. Clinics (São Paulo, Brazil), 68, 123–126.
Anderson, M. S., & Bluestone, J. A. (2005). The NOD mouse: A model of immune dysregulation. Annual Review of Immunology, 23, 447–485.
Baekkeskov, S., Aanstoot, H. J., Christgau, S., Reetz, A., Solimena, M., Cascalho, M., Folli, F., Richterolesen, H., & Camilli, P. D. (1990). Identification of the 64k autoantigen in insulin-dependent diabetes as the GABA-synthesizing enzyme glutamic-acid decarboxylase. Nature, 347, 151–156.
Barrett, J. C., Clayton, D. G., Concannon, P., Akolkar, B., Cooper, J. D., Erlich, H. A., Julier, C., Morahan, G., Nerup, J., Nierras, C., Plagnol, V., Pociot, F., Schuilenburg, H., Smyth, D. J., Stevens, H., Todd, J. A., Walker, N. M., Rich, S. S., & Consortium Type 1 Diabetes Genetics. (2009). Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nature Genetics, 41, 703–707.
Bendelac, A., Boitard, C., Bedossa, P., Bazin, H., Bach, J. F., & Carnaud, C. (1988). Adoptive T cell transfer of autoimmune nonobese diabetic mouse diabetes does not require recruitment of host B lymphocytes. Journal of Immunology, 141(8), 2625.
Bhandary, B., Marahatta, A., Kim, H. R., & Chae, H. J. (2013). An involvement of oxidative stress in endoplasmic reticulum stress and its associated diseases. International Journal of Molecular Sciences, 14, 434–456.
Burton, P. R., Clayton, D. G., Cardon, L. R., Craddock, N., Deloukas, P., Duncanson, A., Kwiatkowski, D. P., McCarthy, M. I., Ouwehand, W. H., Samani, N. J., Todd, J. A., Donnelly, P., Barrett, J. C., Burton, P. R., Davison, D., Donnelly, P., Easton, D., Evans, D., Leung, H. T., Marchini, J. L., Morris, A. P., Spencer, C. C., Tobin, M. D., Cardon, L. R., Clayton, D. G., Attwood, A. P., Boorman, J. P., Cant, B., Everson, U., Hussey, J. M., Jolley, J. D., Knight, A. S., Koch, K., Meech, E., Nutland, S., Prowse, C. V., Stevens, H. E., Taylor, N. C., Walters, G. R., Walker, N. M., Watkins, N. A., Winzer, T., Todd, J. A., Ouwehand, W. H., Jones, R. W., McArdle, W. L., Ring, S. M., Strachan, D. P., Pembrey, M., Breen, G., St Clair, D., Caesar, S., Gordon-Smith, K., Jones, L., Fraser, C., Green, E. K., Grozeva, D., Hamshere, M. L., Holmans, P. A., Jones, I. R., Kirov, G., Moskvina, V., Nikolov, I., O’Donovan, M. C., Owen, M. J., Craddock, N., Collier, D. A., Elkin, A., Farmer, A., Williamson, R., McGuffin, P., Young, A. H., Ferrier, I. N., Ball, S. G., Balmforth, A. J., Barrett, J. H., Bishop, D. T., Iles, M. M., Maqbool, A., Yuldasheva, N., Hall, A. S., Braund, P. S., Burton, P. R., Dixon, R. J., Mangino, M., Suzanne, S., Tobin, M. D., Thompson, J. R., Samani, N. J., Bredin, F., Tremelling, M., Parkes, M., Drummond, H., Lees, C. W., Nimmo, E. R., Satsangi, J., Fisher, S. A., Forbes, A., Lewis, C. M., Onnie, C. M., Prescott, N. J., Sanderson, J., Mathew, C. G., Barbour, J., Mohiuddin, M. K., Todhunter, C. E., Mansfield, J. C., Ahmad, T., Cummings, F. R., Jewell, D. P., Webster, J., Brown, M. J., Clayton, D. G., Lathrop, G. M., Connell, J., Dominczak, A., Samani, N. J., Marcano, C. A., Burke, B., Dobson, R., Gungadoo, J., Lee, K. L., Munroe, P. B., Newhouse, S. J., Onipinla, A., Wallace, C., Xue, M., Caulfield, M., Farrall, M., Barton, A., Bruce, I. N., Donovan, H., Eyre, S., Gilbert, P. D., Hider, S. L., Hinks, A. M., John, S. L., Potter, C., Silman, A. J., Symmmons, D. P., Thomson, W., Worthington, J., Clayton, D. G., Dunger, D. B., Nutland, S., Stevens, H. E., Walker, N. M., Widmer, B., Todd, J. A., Frayling, T. A., Freathy, R. M., Lango, H., Perry, J. R., Shields, B. M., Weedon, M. N., Hattersley, A. T., Hitman, G. A., Walker, M., Elliott, K. S., Groves, C. J., Lindgren, C. M., Rayner, N. W., Timpson, N. J., Zeggini, E., McCarthy, M. I., Newport, M., Sirugo, G., Lyons, E., Vannberg, F., Hill, A. V., Bradbury, L. A., Farrar, C., Pointon, J. J., Wordsworth, P., Brown, M. A., Franklyn, J. A., Heward, J. M., Simmonds, M. J., Gough, S. C., Seal, S., Stratton, M. R., Rahman, N., Ban, M., Goris, A., Sawcer, S. J., Compston, A., Conway, D., Jallow, M., Newport, M., Sirugo, G., Rockett, K. A., Kwiatowski, D. P., Bumpstead, S. J., Chaney, A., Downes, K., Ghori, M. J., Gwilliam, R., Hunt, S. E., Inouye, M., Keniry, A., King, E., McGinnis, R., Potter, S., Ravindrarajah, R., Whittaker, P., Widden, C., Withers, D., Deloukas, P., Leung, H. T., Nutland, S., Stevens, H. E., Walker, N. M., Todd, J. A., Easton, D., Clayton, D. G., Burton, P. R., Tobin, M. D., Barrett, J. C., Evans, D., Morris, A. P., Cardon, L. R., Cardin, N. J., Davison, D., Ferreira, T., Pereira-Gale, J., Hallgrimsdottir, I. B., Howie, B. N., Marchini, J. L., Spencer, C. C., Su, Z., Teo, Y. Y., Vukcevic, D., Donnelly, P., Bentley, D., Brown, M. A., Gordon, L. R., Caulfield, M., Clayton, D. G., Compston, A., Craddock, N., Deloukas, P., Donnelly, P., Farrall, M., Gough, S. C., Hall, A. S., Hattersley, A. T., Hill, A. V., Kwiatkowski, D. P., Mathew, C., McCarthy, M. I., Ouwehand, W. H., Parkes, M., Pembrey, M., Rahman, N., Samani, N. J., Stratton, M. R., Todd, J. A., & Worthington, J. (2007). Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature, 447, 661–678.
Chiang, J. L., Kirkman, M. S., Laffel, L. M. B., & Peters, A. L. (2014). Type 1 diabetes through the life span: A position statement of the American Diabetes Association. Diabetes Care, 37, 2034–2054.
Chow, I. T., Yang, J., Gates, T. J., James, E. A., Mai, D. T., Greenbaum, C., & Kwok, W. W. (2014). Assessment of CD4+ T cell responses to glutamic acid decarboxylase 65 using DQ8 tetramers reveals a pathogenic role of GAD65 121-140 and GAD65 250-266 in T1D development. PloS One, 9, e112882.
Clancy, K. W., Weerapana, E., & Thompson, P. R. (2016). Detection and identification of protein citrullination in complex biological systems. Current Opinion in Chemical Biology, 30, 1–6.
Coppieters, K. T., Dotta, F., Amirian, N., Campbell, P. D., Kay, T. W., Atkinson, M. A., Roep, B. O., & von Herrath, M. G. (2012). Demonstration of islet-autoreactive CD8 T cells in insulitic lesions from recent onset and long-term type 1 diabetes patients. The Journal of Experimental Medicine, 209, 51–60.
Couper, J. J. (2001). Environmental triggers of type 1 diabetes. Journal of Paediatrics and Child Health, 37, 218–220.
Dang, M. L., Rockell, J., Wagner, R., Wenzlau, J. M., Yu, L., Hutton, J. C., Gottlieb, P. A., & Davidson, H. W. (2011). Human type 1 diabetes is associated with t cell autoimmunity to zinc transporter 8. Journal of Immunology, 186, 6056–6063.
Danke, N. A., Koelle, D. M., Yee, C., Beheray, S., & Kwok, W. W. (2004). Autoreactive T cells in healthy individuals. Journal of Immunology, 172, 5967–5972.
Defronzo, R. A., Tobin, J. D., & Andres, R. (1979). Glucose clamp technique - method for quantifying insulin-secretion and resistance. American Journal of Physiology, 237, E214–EE23.
Delong, T., Baker, R. L., Reisdorph, N., Reisdorph, R., Powell, R. L., Armstrong, M., Barbour, G., Bradley, B., & Haskins, K. (2011). Islet amyloid polypeptide is a target antigen for diabetogenic CD4+ T cells. Diabetes, 60, 2325–2330.
Delong, T., Baker, R. L., He, J., Barbour, G., Bradley, B., & Haskins, K. (2012). Diabetogenic T-cell clones recognize an altered peptide of chromogranin A. Diabetes, 61, 3239–3246.
Diagnosis and classification of diabetes mellitus. (2012). Diabetes Care, 35(Suppl 1), S64–S71.
Doyle, H. A., & Mamula, M. J. (2012). Autoantigenesis: The evolution of protein modifications in autoimmune disease. Current Opinion in Immunology, 24, 112–118.
Driver, J. P., Chen, Y.-G., & Mathews, C. E. (2012). Comparative genetics: Synergizing human and NOD mouse studies for identifying genetic causation of type 1 diabetes. The Review of Diabetic Studies: RDS, 9, 169–187.
Durinovic-Bello, I., Schlosser, M., Riedl, M., Maisel, N., Rosinger, S., Kalbacher, H., Deeg, M., Ziegler, M., Elliott, J., Roep, B. O., Karges, W., & Boehm, B. O. (2004). Pro- and anti-inflammatory cytokine production by autoimmune T cells against preproinsulin in HLA-DRB1*04, DQ8 type 1 diabetes. Diabetologia, 47, 439–450.
Eisenbarth, G. S. (1986). Type I diabetes mellitus. A chronic autoimmune disease. The New England Journal of Medicine, 314, 1360–1368.
Gough, S. C., & Simmonds, M. J. (2007). The HLA region and autoimmune disease: Associations and mechanisms of action. Current Genomics, 8, 453–465.
Hawa, M. I., Kolb, H., Schloot, N., Beyan, H., Paschou, S. A., Buzzetti, R., Mauricio, D., De Leiva, A., Yderstraede, K., Beck-Neilsen, H., Tuomilehto, J., Sarti, C., Thivolet, C., Hadden, D., Hunter, S., Schernthaner, G., Scherbaum, W. A., Williams, R., Brophy, S., Pozzilli, P., & Leslie, R. D. (2013). Adult-onset autoimmune diabetes in Europe is prevalent with a broad clinical phenotype: Action LADA 7. Diabetes Care, 36, 908–913.
Hayashi, H., Morioka, M., Ichimiya, S., Yamato, K., Hinode, D., Nagata, A., & Nakamura, R. (1993). Participation of an arginyl residue of insulin chain-B in the inhibition of hemagglutination by porphyromonas-gingivalis. Oral Microbiology and Immunology, 8, 386–389.
Hensen, S. M. M., & Pruijn, G. J. M. (2014). Methods for the detection of peptidylarginine deiminase (PAD) activity and protein citrullination. Molecular & Cellular Proteomics, 13, 388–396.
Herzog, B. A., Ott, P. A., Dittrich, M. T., Quast, S., Karulin, A. Y., Kalbacher, H., Karges, W., Tary-Lehmann, M., Lehmann, P. V., Boehm, B. O., & Durinovic-Bello, I. (2004). Increased in vivo frequency of IA-2 peptide-reactive IFN gamma(+)/IL-4(−) T cells in type 1 diabetic subjects. Journal of Autoimmunity, 23, 45–54.
Hill, J. A., Southwood, S., Sette, A., Jevnikar, A. M., Bell, D. A., & Cairns, E. (2003). Cutting edge: The conversion of arginine to citrulline allows for a high-affinity peptide interaction with the rheumatoid arthritis-associated HLA-DRB1*0401 MHC class II molecule. Journal of Immunology, 171, 538–541.
Ireland, J., Herzog, J., & Unanue, E. R. (2006). Cutting edge: Unique T cells that recognize citrullinated peptides are a feature of protein immunization. Journal of Immunology, 177, 1421–1425.
James, E. A., Moustakas, A. K., Bui, J., Papadopoulos, G. K., Bondinas, G., Buckner, J. H., & Kwok, W. W. (2010). HLA-DR1001 presents “altered-self” peptides derived from joint-associated proteins by accepting citrulline in three of its binding pockets. Arthritis and Rheumatism, 62, 2909–2918.
James, E. A., Rieck, M., Pieper, J., Gebe, J. A., Yue, B. B., Tatum, M., Peda, M., Sandin, C., Klareskog, L., Malmstrom, V., & Buckner, J. H. (2014). Citrulline-specific Th1 cells are increased in rheumatoid arthritis and their frequency is influenced by disease duration and therapy. Arthritis & Rhematology, 66, 1712–1722.
Kachapati, K., Adams, D., Bednar, K., & Ridgway, W. M. (2012). The non-obese diabetic (NOD) mouse as a model of human type 1 diabetes. Methods in Molecular Biology, 933, 3–16.
Koczwara, K., Bonifacio, E., & Ziegler, A. G. (2004). Transmission of maternal islet antibodies and risk of autoimmune diabetes in offspring of mothers with type 1 diabetes. Diabetes, 53, 1–4.
Lee, A. S. (2005). The ER chaperone and signaling regulator GRP78/BiP as a monitor of endoplasmic reticulum stress. Methods, 35, 373–381.
Li, Y., Zhou, L., Li, Y., Zhang, J., Guo, B., Meng, G., Chen, X., Zheng, Q., Zhang, L., Zhang, M., & Wang, L. (2015). Identification of autoreactive CD8(+) T cell responses targeting chromogranin a in humanized NOD mice and type 1 diabetes patients. Clinical Immunology, 159, 63–71.
Liao, K. P., Gunnarsson, M., Kallberg, H., Ding, B., Plenge, R. M., Padyukov, L., Karlson, E. W., Klareskog, L., Askling, J., & Alfredsson, L. (2009). Specific association of type 1 diabetes mellitus with anti-cyclic citrullinated peptide-positive rheumatoid arthritis. Arthritis and Rheumatism, 60, 653–660.
Lieberman, S. M., Evans, A. M., Han, B. Y., Takaki, T., Vinnitskaya, Y., Caldwell, J. A., Serreze, D. V., Shabanowitz, J., Hunt, D. F., Nathenson, S. G., Santamaria, P., & DiLorenzo, T. P. (2003). Identification of the beta cell antigen targeted by a prevalent population of pathogenic CD8(+) T cells in autoimmune diabetes. Proceedings of the National Academy of Sciences of the United States of America, 100, 8384–8388.
Lipson, K. L., Fonseca, S. G., & Urano, F. (2006). Endoplasmic reticulum stress-induced apoptosis and auto-immunity in diabetes. Current Molecular Medicine, 6, 71–77.
Lohmann, T., Leslie, R. D. G., Hawa, M., Geysen, M., Rodda, S., & Londei, M. (1994). Immunodominant epitopes of glutamic-acid decarboxylase-65 and decarboxylase-67 in insulin-dependent diabetes-mellitus. Lancet, 343, 1607–1608.
Maahs, D. M., West, N. A., Lawrence, J. M., & Mayer-Davis, E. J. (2010). Epidemiology of type 1 diabetes. Endocrinology and Metabolism Clinics of North America, 39, 481–497.
Mannering, S. I., Harrison, L. C., Williamson, N. A., Morris, J. S., Thearle, D. J., Jensen, K. P., Kay, T. W., Rossjohn, J., Falk, B. A., Nepom, G. T., & Purcell, A. W. (2005). The insulin A-chain epitope recognized by human T cells is posttranslationally modified. The Journal of Experimental Medicine, 202, 1191–1197.
Mannering, S. I., Wong, F. S., Durinovic-Bello, I., Brooks-Worrell, B., Tree, T. I., Cilio, C. M., Schloot, N. C., & Mallone, R. (2010). Current approaches to measuring human islet-antigen specific T cell function in type 1 diabetes. Clinical and Experimental Immunology, 162, 197–209.
Marre, M. L., Profozich, J. L., Coneybeer, J. T., Geng, X., Bertera, S., Ford, M. J., Trucco, M., & Piganelli, J. D. (2016). Inherent ER stress in pancreatic islet beta cells causes self-recognition by autoreactive T cells in type 1 diabetes. Journal of Autoimmunity, 72, 33–46.
McGinty, J. W., Chow, I. T., Greenbaum, C., Odegard, J., Kwok, W. W., & James, E. A. (2014). Recognition of posttranslationally modified GAD65 epitopes in subjects with type 1 diabetes. Diabetes, 63, 3033–3040.
Nakayama, M., Abiru, N., Moriyama, H., Babaya, N., Liu, E., Miao, D. M., Yu, L. P., Wegmann, D. R., Hutton, J. C., Elliott, J. F., & Eisenbarth, G. S. (2005). Prime role for an insulin epitope in the development of type 1 diabetes in NOD mice. Nature, 435, 220–223.
Pathiraja, V., Kuehlich, J. P., Campbell, P. D., Krishnamurthy, B., Loudovaris, T., Coates, P. T., Brodnicki, T. C., O’Connell, P. J., Kedzierska, K., Rodda, C., Bergman, P., Hill, E., Purcell, A. W., Dudek, N. L., Thomas, H. E., Kay, T. W., & Mannering, S. I. (2015). Proinsulin-specific, HLA-DQ8, and HLA-DQ8-transdimer-restricted CD4+ T cells infiltrate islets in type 1 diabetes. Diabetes, 64, 172–182.
Pearson, J. A., Wong, F. S., & Wen, L. (2016). The importance of the non obese diabetic (NOD) mouse model in autoimmune diabetes. Journal of Autoimmunity, 66, 76–88.
Peng, H., & Hagopian, W. (2006). Environmental factors in the development of type 1 diabetes. Reviews in Endocrine & Metabolic Disorders, 7, 149–162.
Petersen, J., Purcell, A. W., & Rossjohn, J. (2009). Post-translationally modified T cell epitopes: Immune recognition and immunotherapy. Journal of Molecular Medicine (Berlin), 87, 1045–1051.
Reed, J. C., & Herold, K. C. (2015). Thinking bedside at the bench: The NOD mouse model of T1DM. Nature Reviews Endocrinology, 11, 308–314.
Reijonen, H., Mallone, R., Heninger, A. K., Laughlin, E. M., Kochik, S. A., Falk, B., Kwok, W. W., Greenbaum, C., & Nepom, G. T. (2004). GAD65-specific CD4(+) T-cells with high antigen avidity are prevalent in peripheral blood of patients with type 1 diabetes. Diabetes, 53, 1987–1994.
Roep, B. O., & Tree, T. I. M. (2014). Immune modulation in humans: Implications for type 1 diabetes mellitus. Nature Reviews Endocrinology, 10, 229–242.
Romero, V., Fert-Bober, J., Nigrovic, P. A., Darrah, E., Haque, U. J., Lee, D. M., van Eyk, J., Rosen, A., & Andrade, F. (2013). Immune-mediated pore-forming pathways induce cellular hypercitrullination and generate citrullinated autoantigens in rheumatoid arthritis. Science Translational Medicine, 5, 209ra150.
Ronda, D., Crèvecoeur, I., D’Hertog, W., Ferreira, G. B., Staes, A., Garg, A. D., Eizirik, D. L., Agostinis, P., Gevaert, K., Overbergh, L., & Mathieu, C. (2015). Citrullinated glucose-regulated protein 78 is an autoantigen in type 1 diabetes. Diabetes, 64, 573–586.
Sabbah, E., Savola, K., Kulmala, P., Veijola, R., Vahasalo, P., Karjalainen, J., Akerblom, H. K., Knip, M., & Grp Childhood Diabetes Finland Study. (1999). Diabetes-associated autoantibodies in relation to clinical characteristics and natural course in children with newly diagnosed type 1 diabetes. The childhood diabetes in Finland study group. Journal of Clinical Endocrinology & Metabolism, 84, 1534–1539.
Scally, S. W., Petersen, J., Law, S. C., Dudek, N. L., Nel, H. J., Loh, K. L., Wijeyewickrema, L. C., Eckle, S. B. G., van Heemst, J., Pike, R. N., McCluskey, J., Toes, R. E., La Gruta, N. L., Purcell, A. W., Reid, H. H., Thomas, R., & Rossjohn, J. (2013). A molecular basis for the association of the HLA-DRB1 locus, citrullination, and rheumatoid arthritis. Journal of Experimental Medicine, 210, 2569–2582.
Schloot, N. C., Willemen, S., Duinkerken, G., de Vries, R. R. P., & Roep, B. O. (1998). Cloned T cells from a recent onset IDDM patient reactive with insulin B-chain. Journal of Autoimmunity, 11, 169–175.
Scotto, M., Afonso, G., Larger, E., Raverdy, C., Lemonnier, F. A., Carel, J. C., Dubois-Laforgue, D., Baz, B., Levy, D., Gautier, J. F., Launay, O., Bruno, G., Boitard, C., Sechi, L. A., Hutton, J. C., Davidson, H. W., & Mallone, R. (2012). Zinc transporter (ZnT)8(186-194) is an immunodominant CD8(+) T cell epitope in HLA-A2(+) type 1 diabetic patients. Diabetologia, 55, 2026–2031.
Sette, A., Moutaftsi, M., Moyron-Quiroz, J., McCausland, M. M., Davies, D. H., Johnston, R. J., Peters, L., Rafii-El-Idrissi Benhnia, M., Hoffmann, J., Su, H.-P., Singh, K., Garboczi, D. N., Head, S., Grey, H., Felgner, P. L., & Crotty, S. (2008). Selective CD4(+) T cell help for antibody responses to a large viral pathogen: Deterministic linkage of specificities. Immunity, 28, 847–858.
Shoda, H., Fujio, K., Sakurai, K., Ishigaki, K., Nagafuchi, Y., Shibuya, M., Sumitomo, S., Okamura, T., & Yamamoto, K. (2015). Autoantigen BiP-derived HLA-DR4 epitopes differentially recognized by effector and regulatory T cells in rheumatoid arthritis. Arthritis & Rhematology, 67, 1171–1181.
Snir, O., Widhe, M., von Spee, C., Lindberg, J., Padyukov, L., Lundberg, K., Engstrom, A., Venables, P. J., Lundeberg, J., Holmdahl, R., Klareskog, L., & Malmstrom, V. (2009). Multiple antibody reactivities to citrullinated antigens in sera from patients with rheumatoid arthritis: Association with HLA-DRB1 alleles. Annals of the Rheumatic Diseases, 68, 736–743.
Stadinski, B. D., Delong, T., Reisdorph, N., Reisdorph, R., Powell, R. L., Armstrong, M., Piganelli, J. D., Barbour, G., Bradley, B., Crawford, F., Marrack, P., Mahata, S. K., Kappler, J. W., & Haskins, K. (2010). Chromogranin a is an autoantigen in type 1 diabetes. Nature Immunology, 11, 225–2U5.
Strollo, R., Vinci, C., Arshad, M. H., Perrett, D., Tiberti, C., Chiarelli, F., Napoli, N., Pozzilli, P., & Nissim, A. (2015). Antibodies to post-translationally modified insulin in type 1 diabetes. Diabetologia, 58, 2851–2860.
Szekanecz, Z., Soos, L., Szabo, Z., Fekete, A., Kapitany, A., Vegvari, A., Sipka, S., Szucs, G., Szanto, S., & Lakos, G. (2008). Anti-citrullinated protein antibodies in rheumatoid arthritis: As good as it gets? Clinical Reviews in Allergy & Immunology, 34, 26–31.
Uchtenhagen, H., Rims, C., Blahnik, G., Chow, I. T., Kwok, W. W., Buckner, J. H., & James, E. A. (2016). Efficient ex vivo analysis of CD4+ T-cell responses using combinatorial HLA class II tetramer staining. Nature Communications, 7, 12614.
van Belle, T. L., Coppieters, K. T., & von Herrath, M. G. (2011). Type 1 diabetes: Etiology, immunology, and therapeutic strategies. Physiological Reviews, 91, 79–118.
van Kuppeveld, F. J. M., Hoenderop, J. G. J., Smeets, R. L. L., Willems, P., Dijkman, H., Galama, J. M. D., & Melchers, W. J. G. (1997). Coxsackievirus protein 2B modifies endoplasmic reticulum membrane and plasma membrane permeability and facilitates virus release. EMBO Journal, 16, 3519–3532.
van Kuppeveld, F. J., de Jong, A. S., Melchers, W. J., & Willems, P. H. (2005). Enterovirus protein 2B po(u)res out the calcium: A viral strategy to survive? Trends in Microbiology, 13, 41–44.
van Lummel, M., Duinkerken, G., van Veelen, P. A., de Ru, A., Cordfunke, R., Zaldumbide, A., Gomez-Touriño, I., Arif, S., Peakman, M., Drijfhout, J. W., & Roep, B. O. (2014). Posttranslational modification of HLA-DQ binding islet autoantigens in type 1 diabetes. Diabetes, 63, 237–247.
Vossenaar, E. R., Zendman, A. J. W., van Venrooij, W. J., & Pruijn, G. J. M. (2003). PAD, a growing family of citrullinating enzymes: Genes, features and involvement in disease. BioEssays, 25, 1106–1118.
Vossenaar, E. R., Radstake, T. R., van der Heijden, A., van Mansum, M. A., Dieteren, C., de Rooij, D. J., Barrera, P., Zendman, A. J., & van Venrooij, W. J. (2004). Expression and activity of citrullinating peptidylarginine deiminase enzymes in monocytes and macrophages. Annals of the Rheumatic Diseases, 63, 373–381.
Wang, Q., Zhang, H., Zhao, B., & Fei, H. (2009). IL-1beta caused pancreatic beta-cells apoptosis is mediated in part by endoplasmic reticulum stress via the induction of endoplasmic reticulum Ca2+ release through the c-Jun N-terminal kinase pathway. Molecular and Cellular Biochemistry, 324, 183–190.
Wegmann, D. R., Norburyglaser, M., & Daniel, D. (1994). Insulin-specific T-cells are a predominant component of islet infiltrates in prediabetic NOD mice. European Journal of Immunology, 24, 1853–1857.
Willcox, A., Richardson, S. J., Bone, A. J., Foulis, A. K., & Morgan, N. G. (2009). Analysis of islet inflammation in human type 1 diabetes. Clinical and Experimental Immunology, 155, 173–181.
Wong, S. L., Demers, M., Martinod, K., Gallant, M., Wang, Y., Goldfine, A. B., Kahn, C. R., & Wagner, D. D. (2015). Diabetes primes neutrophils to undergo NETosis, which impairs wound healing. Nature Medicine, 21, 815–819.
Wu, J., & Kaufman, R. J. (2006). From acute ER stress to physiological roles of the unfolded protein response. Cell Death and Differentiation, 13, 374–384.
Yang, J. B., Danke, N. A., Berger, D., Reichstetter, S., Reijonen, H., Greenbaum, C., Pihoker, C., James, E. A., & Kwok, W. W. (2006). Islet-specific glucose-6-phosphatase catalytic subunit-related protein-reactive CD4(+) T cells in human subjects. Journal of Immunology, 176, 2781–2789.
Yang, J., Danke, N., Roti, M., Huston, L., Greenbaum, C., Pihoker, C., James, E. A., & Kwok, W. W. (2008). CD4+ T cells from type 1 diabetic and healthy subjects exhibit different thresholds of activation to a naturally processed proinsulin epitope. Journal of Autoimmunity, 31, 30–41.
Yang, J., James, E. A., Sanda, S., Greenbaum, C., & Kwok, W. W. (2013). CD4+ T cells recognize diverse epitopes within GAD65: Implications for repertoire development and diabetes monitoring. Immunology, 138, 269–279.
Yang, J., Chow, I. T., Sosinowski, T., Torres-Chinn, N., Greenbaum, C. J., James, E. A., Kappler, J. W., Davidson, H. W., & Kwok, W. W. (2014). Autoreactive T cells specific for insulin B:11-23 recognize a low-affinity peptide register in human subjects with autoimmune diabetes. Proceedings of the National Academy of Sciences of the United States of America, 111, 14840–14845.
Yu, L. P., Dong, F., Miao, D. M., Fouts, A. R., Wenzlau, J. M., & Steck, A. K. (2013). Proinsulin/insulin autoantibodies measured with electrochemiluminescent assay are the earliest indicator of prediabetic islet autoimmunity. Diabetes Care, 36, 2266–2270.
Zhao, Z., Miao, D., Michels, A., Steck, A., Dong, F., Rewers, M., & Yu, L. (2016). A multiplex assay combining insulin, GAD, IA-2 and transglutaminase autoantibodies to facilitate screening for pre-type 1 diabetes and celiac disease. Journal of Immunological Methods, 430, 28–32.
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Nguyen, H., James, E.A. (2017). Antigen Deimination in Human Type 1 Diabetes and Nonobese Diabetic Mice. In: Nicholas, A., Bhattacharya, S., Thompson, P. (eds) Protein Deimination in Human Health and Disease. Springer, Cham. https://doi.org/10.1007/978-3-319-58244-3_10
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