The glomerulonephritis disease is characterized by inflammation of glomeruli or small blood vessels in the kidney that causes kidney diseases. The reason of glomerulonephritis disease is to deposit the anti-GBM auto antibody in the glomerular basement membrane. The type IV collagen is the main component of glomerular basement membrane that has α3 chain of type (IV) collagen of non-collagenous domain which contains N-terminal 7S domain, a triple helical collagenous domain and C-terminal non-collagenous glomerular domain (NC1). The amino terminal of α3 (IV) NC1 that induces the Experimental Autoimmuno Glomerulonephritis (EAG) in rat model has been identified. The recombinant rat α3 (IV) NC1 antigen has nine amino acid spans that are consistent with antibody or T cell epitope that induces in EAG. The research is carried out on the recombinant rat α3 (IV) NC1 production, purification, quantification, and characterization. The circulation of anti-GBM antibody in glomerular basement membrane can be measured by the ELISA assay. In addition, the recombinant rat antigen is secreted in HEK293 cell supernatant that is purified by Anti-FLAG M2 monoclonal IgG antibody affinity column and characterized and quantified by SDS-PAGE gel electrophoresis and Western blotting techniques.
References
[1]
Salama, A.D. and Pusey, C.D. (2002) Immunology of Anti-Glomerular Membrane Disease. Current Opinion in Nephrology and Hypertension, 11, 279-286. http://dx.doi.org/10.1097/00041552-200205000-00003
Turner, A.N., Mason, P.J. and Brown, R. (1992) Molecular Cloning of the Human Goodpasture Antigen Demonstrates It to Be the Alpha3 Chain of Type IV Collagen. The Journal of Clinical Investigation, 89, 592-601. http://dx.doi.org/10.1172/JCI115625
[4]
Goodpasture, E.W. (1919) The Pathology of Pneumonia Accompanying Influenza. U.S. Naval Medical Bulletin, 13, 177-197.
[5]
Stanton, M.C. and Tange, J.D. (1958) Goodpasture’s Syndrome: Pulmonary Hemorrhage Associated with Glomerulonephritis. Australasian Annals of Medicine, 7, 132-144.
[6]
Saus, J., Wieslanderm, J. and Langeveld, J.P. (1998) Identification of the Goodpasture Antigen as the Alpha3(IV) Chain of Collagen IV. The Journal of Biological Chemistry, 263, 13374-13380.
[7]
Abbate, M., Kalluri, R., Corna, D., Yamaguchi, N., McCluskey, R.T., Hudson, B.G., Andres, G., Zoja, C. and Remuzzi, G. (1998) Experimental Goodpasture’s Syndrome in Wistar-Kyoto Rats Immunized with Alpha3 Chain of Type IV Collagen. Kidney International, 54, 1550-1561. http://dx.doi.org/10.1046/j.1523-1755.1998.00153.x
[8]
Ryan, J.J., Reynolds, J., Norgan, V.A. and Pusey, C.D. (2001) Expression and Characterization of Recombinant Rat Alpha3(IV)NC1 and Its Use in the Induction of Experimental Autoimmune Glomerulonephritis. Nephrology Dialysis Transplantation, 16, 253-261. http://dx.doi.org/10.1093/ndt/16.2.253
[9]
Hudson, B.G. and Reeders, S.T. (1993) Type IV Collagen: Structure Gene Organization, and Role in Human Diseases, Molecular Basis of Goodpasture and Alport Syndromes and Diffuse Leiomyomatosis. The Journal of Biological Chemistry, 268, 26033-26036.
[10]
Borza, D.B., Bondar, O., Colon, S., Todd, P., Sado, Y., Neilson, E.G. and Hudson, B.G. (2000) The Goodpasture Autoantigen. Identification of Multiple Cryptic Epitopes on the NC1 Domain of the Alpha3(IV) Collagen Chain. The Journal of Biological Chemistry, 275, 6030-6037. http://dx.doi.org/10.1074/jbc.275.8.6030
[11]
Borza, D.B., Bondar, O., Colon, S., Todd, P., Sado, Y., Neilson, E.G. and Hudson, B.G. (2005) Goodpasture Autoantibodies Unmask Cryptic Epitopes by Selectively Dissociating Autoantigen Complexes Lacking Structural Reinforcement: Novel Mechanisms for Immune Privilege and Autoimmune Pathogenesis. The Journal of Biological Chemistry, 280, 27147-27154. http://dx.doi.org/10.1074/jbc.M504050200
[12]
Reynolds, J., Mavromatidis, K., Cashman, S.J., Evans, D.J. and Pusey, C.D. (1998) Experimental Autoimmune Glomerulonephritis (EAG) Induced by Homologous Glomerular Basement Membrane in Two Sub Strains of Wistar-Kyoto Rat. Nephrology Dialysis Transplantation, 13, 44-52. http://dx.doi.org/10.1093/ndt/13.1.44
[13]
Hudson, B.G. (1998) Induction of Anti-GBM Nephritis in Rats by Recombinant Alpha3(IV) and Alpha4(IV)NC1 of Type IV Collagen. Kidney International, 53, 664-671. http://dx.doi.org/10.1046/j.1523-1755.1998.00795.x
[14]
Hellmark, T., Brunmark, C., Trojnar, J. and Wieslander, J. (1996) Epitope Mapping of Anti-Glomerular Basement Membrane (GBM) Antibodies with Synthetic Peptides. Clinical & Experimental Immunology, 105, 504-510. http://dx.doi.org/10.1046/j.1365-2249.1996.119808.x
[15]
Kalluri, R., Gunwar, S. and Reders, S.T. (1991) Goodpasture Syndrome. Localization of the Epitope for the Autoantibodies to the Carboxyl Terminal Region of the α3(IV) Chain Basement Collagen. The Journal of Biological Chemistry, 266, 24018-24024.
[16]
Kefalides, N.A., Ohno, N. and Wilson, C.B. (1993) Heterogeneity of Antibodies in Goodpasture Syndrome Reacting with Type IV Collagen. Kidney International, 43, 85-93. http://dx.doi.org/10.1038/ki.1993.15
[17]
Levy, J.B., Coulhart, A. and Pusey, C.D. (1997) Mapping B Cell Epitopes in Goodpasture’s Disease. Journal of the American Society of Nephrology, 8, 1698-1705.
[18]
Hellmark, T., Segelmark, M. and Unger, C. (1999) Identification of a Clinically Relevant Immunodominant Region of Collagen IV in Goodpasture Disease. Kidney International, 55, 936-944. http://dx.doi.org/10.1046/j.1523-1755.1999.055003936.x
[19]
Borza, D.B., Bondar, O., Todd, P., Sundaramoorthy, M., Sado, Y., Ninomiya, Y. and Hudson, B.G. (2002) Quaternary Organization of the Goodpasture Autoantigen, the Alpha3(IV) Collagen Chain. Sequestration of Two Cryptic Autoepitopes by Intraprotomer Interactions with the Alpha4 and Alpha5NC1 Domains. The Journal of Biological Chemistry, 277, 40075-40083. http://dx.doi.org/10.1074/jbc.M207769200
[20]
Leinonen, A., Netzer, K.O. and Boutaud, A. (1999) Goodpasture Antigen: Expression of the Full Length α3(IV) Chain of Collagen IV and Localization of Epitopes Exclusively of the Noncollagenous Domain. Kidney International, 55, 926-935. http://dx.doi.org/10.1046/j.1523-1755.1999.055003926.x
[21]
Steblay, R.W. (1962) Glomerulonephritis Induced in Sheep by Injections of Heterologous Glomerular Basement Membrane and Freund’s Complete Adjuvant. The Journal of Experimental Medicine, 116, 253-271. http://dx.doi.org/10.1084/jem.116.2.253
[22]
Sado, Y., Naito, I. and Okigaki, T. (1989) Transfer of Anti-Glomerular Basement Membrane Antibody-Induced Glomerulonephritis in Inbred Rats with Isologous Antibodies from the Urine of Nephritic Rats. The Journal of Pathology, 159, 325-332. http://dx.doi.org/10.1002/path.1711580410
Yokoyama, H., Wada, T., Zhang, W., Yamaya, H. and Asaka, M. (2007) Advance in Apheresis Therapy for Glomerular Diseases. Clinical and Experimental Nephrology, 11, 122-127. http://dx.doi.org/10.1007/s10157-007-0462-y
[25]
Johnson, J.P., Moore Jr., J., Austin, H.A.III, Antonovych, T.T. and Wilson, C.B. (1985) Therapy of Anti-Glomerular Basement Membrane Antibody Disease: Analysis of Prognostic Significance of Clinical, Pathologic and Treatment Factors. Medicine (Baltimore), 64, 219-227. http://dx.doi.org/10.1097/00005792-198507000-00003
[26]
Levy, J.B., Turner A.N., Rees, A.J. and Pusey, C.D. (2001) Long Term Outcome of Anti-Glomerular Basement Membrane Antibody Disease Treated with Plasma Exchange and Immunosuppression. Annals of Internal Medicine, 134, 1033-1042. http://dx.doi.org/10.7326/0003-4819-134-11-200106050-00009
[27]
Kalluri, R., Danoff, T.M., Okada, H. and Neilson, E.G. (1997) Susceptibility to Anti-Glomerular Basement Disease and Goodpasture’s Syndrome Is Linked to MHC Class II Genes and the Emergence of T Cell-Mediated Immunity in Mice. The Journal of Clinical Investigation, 100, 2263-2275. http://dx.doi.org/10.1172/JCI119764
[28]
Fritze, C.E. and Anderson, T.R. (2000) Epitope Tagging: General Method for Tracking Recombinant Proteins. Methods in Enzymology, 327, 3-16. http://dx.doi.org/10.1016/S0076-6879(00)27263-7
[29]
Einhauer, A. and Jungbauer, A. (2001) The FLAG Peptide, a Versatile Fusion Tag for the Purification of Recombinant Proteins. Journal of Biochemical and Biophysical Methods, 49, 455-465. http://dx.doi.org/10.1016/S0165-022X(01)00213-5
[30]
Kalluri, R., Gattone, V.H.II, Noelken, M.E. and Hudson, B.G. (1994) The α3 Chain of Type IV Collagen Induces Autoimmune Goodpasture Syndrome. Proceedings of the National Academy of Sciences of the United States of America, 91, 6201-6205.
[31]
Hellmark, T., Johansson, C. and Wieslander, J. (1994) Characterization of Anti-GBM Antibodies Involved in Goodpasture’s Syndrome. Kidney International, 46, 823-829. http://dx.doi.org/10.1038/ki.1994.338
[32]
Dehan, P., Weber, M., Zhang, X., Reeders, S.T., Foidart, J.M. and Tryggvason, K. (1996) Sera from Patients with Anti-GBM Nephritis Including Goodpasture’s Syndrome Show Heterogenous Reactivity to Recombinant NC1 Domain of Type IV Collagen Alpha Chains. Nephrology Dialysis Transplantation, 11, 2215-2222. http://dx.doi.org/10.1093/oxfordjournals.ndt.a027139
[33]
Chen, L., Hellmark, T. and Bolton, W.K. (2003) Immunodominant Epitopes of α3(IV)NC1 Induce Autoimmune Glomerulonephritis in Rats. Kidney International, 64, 2108-2120. http://dx.doi.org/10.1046/j.1523-1755.2003.00332.x
[34]
Reynolds, J., Prodromidi, I.E., Juggapah, K.J., Abbott, S.D., Holthaus, A.K., Kalluri, R. and Pusy, D.C. (2005) Nasal Administration of Recombinant Rat α3(IV)NC1 Prevents the Development of Experimental Autoimmune Glomerulonephritis in the WKY Rat. Journal of the American Society of Nephrology, 16, 1350-1359. http://dx.doi.org/10.1681/ASN.2004121026
[35]
Myers, L.K., Stuart, J.M., Seyer, J.M. and Kang, A.H. (1989) Identification of an Immunosuppressive Epitope of Type II Collagen That Confers Protection against Collagen-Induced Arthritis. The Journal of Experimental Medicine, 170, 1999-20104. http://dx.doi.org/10.1084/jem.170.6.1999
[36]
Gaur, A., Wiers, B., Liu, A., Rothbard, J. and Fathman, C.G. (1992) Amelioration of Autoimmune Encephalomyelitis by Myelin Basic Protein Synthetic Peptide-Induced Anergy. Science, 258, 1491-1494. http://dx.doi.org/10.1126/science.1279812
[37]
Mukasa, A., Itoh, M., Tokunaga, Y., Hiramine, C. and Hojo, K. (1992) Inhibition of a Novel Model of Murine Experimental Autoimmune Orchitis by Intravenous Administration with a Soluble Testicular Antigen: Participation of CD8+ Regulatory T Cells. Clinical Immunology and Immunopathology, 62, 210-219. http://dx.doi.org/10.1016/0090-1229(92)90074-X
[38]
Sasamoto, Y., Kawano, Y.I., Bouligny, R., Wiggert, B., Chader, G.J. and Gery, I. (1992) Immunomodulation of Experimental Autoimmune Uveoretinitis by Intravenous Injection of Uveitogenic Peptides. Investigative Ophthalmology & Visual Science, 33, 2641-2649.
[39]
Fuller, B.E., Okayasu, I., Simon, L.L., Giraldo, A.A. and Kong, Y.M. (1993) Characterization of Resistance to Murine Experimental Autoimmune Thyroiditis: Duration and Afferent Action of Thyroglobulin-and TSH-Induced Suppression. Clinical Immunology and Immunopathology, 69, 60-68. http://dx.doi.org/10.1006/clin.1993.1150
