Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Science 25 April 1997:
Vol. 276. no. 5312, pp. 604 - 607
DOI: 10.1126/science.276.5312.604

Reports

Identification of alpha -Fodrin as a Candidate Autoantigen in Primary Sjögren's Syndrome

Norio Haneji, * Takanori Nakamura, * Koji Takio, Kumiko Yanagi, Hiroyuki Higashiyama, Ichiro Saito, Sumihare Noji, Hiromu Sugino, Yoshio Hayashi dagger

It is unclear whether organ-specific autoantigens are critical for the development of primary Sjögren's syndrome (SS). A 120-kilodalton organ-specific autoantigen was purified from salivary gland tissues of an NFS/sld mouse model of human SS. The amino-terminal residues were identical to those of the human cytoskeletal protein alpha -fodrin. The purified antigen induced proliferative T cell responses and production of interleukin-2 and interferon-gamma in vitro. Neonatal immunization with the 120-kilodalton antigen prevented the disease in mice. Sera from patients with SS reacted positively with purified antigen and recombinant human alpha -fodrin protein, whereas those from patients with systemic lupus erythematosus and rheumatoid arthritis did not. Thus, the immune response to 120-kilodalton alpha -fodrin could be important in the initial development of primary SS.

N. Haneji, K. Yanagi, H. Higashiyama, I. Saito, Y. Hayashi, Department of Pathology, Tokushima University School of Dentistry, 3 Kuramotocho, Tokushima 770, Japan.
T. Nakamura and H. Sugino, Institute for Enzyme Research, University of Tokushima, 3 Kuramotocho, Tokushima 770, Japan.
K. Takio, Division of Biomolecular Characterization, The Institute of Physical and Chemical Research, Wako, Saitama 351-01, Japan.
S. Noji, Division of Biological Industry, University of Tokushima, Jyosanjima, Tokushima 770, Japan.
*   These authors contributed equally to this study.

dagger    To whom correspondence should be addressed. E-mail: hayashi{at}dent.tokushima-u.ac.jp


Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Recent advances in autoimmune pancreatitis.
D H Park, M-H Kim, and S T Chari (2009)
Gut 58, 1680-1689
   Abstract »    Full Text »    PDF »
The Role of Fractalkine as an Accelerating Factor on the Autoimmune Exocrinopathy in Mice.
K. Tsubota, T. Nishiyama, K. Mishima, H. Inoue, T. Doi, Y. Hattori, T. Kodama, A. Higuchi, Y. Hayashi, and I. Saito (2009)
Invest. Ophthalmol. Vis. Sci. 50, 4753-4760
   Abstract »    Full Text »    PDF »
Characterization of Effector T Cells in Dry Eye Disease.
J. El Annan, S. K. Chauhan, T. Ecoiffier, Q. Zhang, D. R. Saban, and R. Dana (2009)
Invest. Ophthalmol. Vis. Sci. 50, 3802-3807
   Abstract »    Full Text »    PDF »
Treatment of sicca symptoms with hydroxychloroquine in patients with Sjogren's syndrome.
M. Rihl, K. Ulbricht, R. E. Schmidt, and T. Witte (2009)
Rheumatology 48, 796-799
   Abstract »    Full Text »    PDF »
In Vitro Expanded CD4+CD25+Foxp3+ Regulatory T Cells Maintain a Normal Phenotype and Suppress Immune-Mediated Ocular Surface Inflammation.
K. F. Siemasko, J. Gao, V. L. Calder, R. Hanna, M. Calonge, S. C. Pflugfelder, J. Y. Niederkorn, and M. E. Stern (2008)
Invest. Ophthalmol. Vis. Sci. 49, 5434-5440
   Abstract »    Full Text »    PDF »
Expression of the retinoblastoma protein RbAp48 in exocrine glands leads to Sjogren's syndrome-like autoimmune exocrinopathy.
N. Ishimaru, R. Arakaki, S. Yoshida, A. Yamada, S. Noji, and Y. Hayashi (2008)
J. Exp. Med. 205, 2915-2927
   Abstract »    Full Text »    PDF »
B-cell involvement in chronic graft-versus-host disease.
R. Kapur, S. Ebeling, and A. Hagenbeek (2008)
Haematologica 93, 1702-1711
   Abstract »    Full Text »    PDF »
Absence of 4 1BB Gene Function Exacerbates Lacrimal Gland Inflammation in Autoimmune-Prone MRL-Faslpr Mice.
D. S. Vinay, J. D. Kim, T. Asai, B. K. Choi, and B. S. Kwon (2007)
Invest. Ophthalmol. Vis. Sci. 48, 4608-4615
   Abstract »    Full Text »    PDF »
Autoimmune Dacryoadenitis of NOD/LtJ Mice and Its Subsequent Effects on Tear Protein Composition.
M. E. Doyle, L. Boggs, R. Attia, L. R. Cooper, D. R. Saban, C. Q. Nguyen, and A. B. Peck (2007)
Am. J. Pathol. 171, 1224-1236
   Abstract »    Full Text »    PDF »
IL-4-STAT6 Signal Transduction-Dependent Induction of the Clinical Phase of Sjogren's Syndrome-Like Disease of the Nonobese Diabetic Mouse.
C. Q. Nguyen, J.-h. Gao, H. Kim, D. R. Saban, J. G. Cornelius, and A. B. Peck (2007)
J. Immunol. 179, 382-390
   Abstract »    Full Text »    PDF »
Clinical and immunological characteristics of patients with Sjogren's syndrome in relation to {alpha}-fodrin antibodies.
P. Willeke, M. Gaubitz, H. Schotte, H. Becker, E. Mickholz, W. Domschke, and B. Schluter (2007)
Rheumatology 46, 479-483
   Abstract »    Full Text »    PDF »
Novel Role for RbAp48 in Tissue-Specific, Estrogen Deficiency-Dependent Apoptosis in the Exocrine Glands.
N. Ishimaru, R. Arakaki, F. Omotehara, K. Yamada, K. Mishima, I. Saito, and Y. Hayashi (2006)
Mol. Cell. Biol. 26, 2924-2935
   Abstract »    Full Text »    PDF »
Antibodies to {alpha}-fodrin derived peptide in Sjogren's syndrome.
J He, Q L Chen, and Z G Li (2006)
Ann Rheum Dis 65, 549-550
   Full Text »    PDF »
Clinical significance of quantitative immunohistology in labial salivary glands for diagnosing Sjogren's syndrome.
J. M. van Woerkom, A. A. Kruize, P. J. Barendregt, L. Kater, R. Hene, H. Bootsma, R. J. H. Custers, J. W. G. Jacobs, and J. W. J. Bijlsma (2006)
Rheumatology 45, 470-477
   Abstract »    Full Text »    PDF »
The wide spectrum of clinical manifestations in Sjogren's syndrome-associated neuropathy.
K. Mori, M. Iijima, H. Koike, N. Hattori, F. Tanaka, H. Watanabe, M. Katsuno, A. Fujita, I. Aiba, A. Ogata, et al. (2005)
Brain 128, 2518-2534
   Abstract »    Full Text »    PDF »
Analysis of in Vivo Role of {alpha}-Fodrin Autoantigen in Primary Sjogren's Syndrome.
K. Miyazaki, N. Takeda, N. Ishimaru, F. Omotehara, R. Arakaki, and Y. Hayashi (2005)
Am. J. Pathol. 167, 1051-1059
   Abstract »    Full Text »    PDF »
Anti-{alpha}-fodrin autoantibodies are not useful diagnostic markers of primary Sjogren's syndrome.
C Sordet, J E Gottenberg, J Goetz, D Bengoufa, R-L Humbel, X Mariette, and J Sibilia (2005)
Ann Rheum Dis 64, 1244-1245
   Full Text »    PDF »
Enhanced autoantigen expression in regenerating muscle cells in idiopathic inflammatory myopathy.
L. Casciola-Rosen, K. Nagaraju, P. Plotz, K. Wang, S. Levine, E. Gabrielson, A. Corse, and A. Rosen (2005)
J. Exp. Med. 201, 591-601
   Abstract »    Full Text »    PDF »
Development of Autoimmunity against Transcriptionally Unrepressed Target Antigen in the Thymus of Aire-Deficient Mice.
N. Kuroda, T. Mitani, N. Takeda, N. Ishimaru, R. Arakaki, Y. Hayashi, Y. Bando, K. Izumi, T. Takahashi, T. Nomura, et al. (2005)
J. Immunol. 174, 1862-1870
   Abstract »    Full Text »    PDF »
Autoimmunity against a Tissue Kallikrein in IQI/Jic Mice: A MODEL FOR SJOGREN'S SYNDROME.
K. Takada, M. Takiguchi, A. Konno, and M. Inaba (2005)
J. Biol. Chem. 280, 3982-3988
   Abstract »    Full Text »    PDF »
E2f1 Mutation Induces Early Onset of Diabetes and Sjogren's Syndrome in Nonobese Diabetic Mice.
M. A. Salam, K. Matin, N. Matsumoto, Y. Tsuha, N. Hanada, and H. Senpuku (2004)
J. Immunol. 173, 4908-4918
   Abstract »    Full Text »    PDF »
Molecular Analysis of the Human Autoantibody Response to {alpha}-Fodrin in Sjogren's Syndrome Reveals Novel Apoptosis-Induced Specificity.
T. Maruyama, I. Saito, Y. Hayashi, E. Kompfner, R. I. Fox, D. R. Burton, and H. J. Ditzel (2004)
Am. J. Pathol. 165, 53-61
   Abstract »    Full Text »    PDF »
ALTERED AUTOANTIGEN STRUCTURE IN SJoGREN'S SYNDROME: IMPLICATIONS FOR THE PATHOGENESIS OF AUTOIMMUNE TISSUE DAMAGE.
A. Rosen and L. Casciola-Rosen (2004)
Critical Reviews in Oral Biology & Medicine 15, 156-164
   Abstract »    Full Text »    PDF »
Use of localised gene transfer to develop new treatment strategies for the salivary component of Sjogren's syndrome.
M R Kok, B J Baum, P P Tak, and S R Pillemer (2003)
Ann Rheum Dis 62, 1038-1046
   Abstract »    Full Text »    PDF »
Development of Autoimmune Exocrinopathy Resembling Sjogren's Syndrome in Estrogen-Deficient Mice of Healthy Background.
N. Ishimaru, R. Arakaki, M. Watanabe, M. Kobayashi, K. Miyazaki, and Y. Hayashi (2003)
Am. J. Pathol. 163, 1481-1490
   Abstract »    Full Text »    PDF »
{alpha}-Fodrin autoantibodies in the differential diagnosis of MS and Sjogren syndrome.
J. de Seze, S. Dubucquoi, A. L. Fauchais, T. Matthias, D. Devos, G. Castelnovo, T. Stojkovic, D. Ferriby, E. Hachulla, P. Labauge, et al. (2003)
Neurology 61, 268-269
   Full Text »    PDF »
Benefit of IVIG for long-standing ataxic sensory neuronopathy with Sjogren's syndrome.
Y. Takahashi, T. Takata, M. Hoshino, M. Sakurai, and I. Kanazawa (2003)
Neurology 60, 503-505
   Abstract »    Full Text »    PDF »
Pathological lymphocyte activation by defective clearance of self-ligands in systemic lupus erythematosus.
K. Yasutomo (2003)
Rheumatology 42, 214-222
   Abstract »    Full Text »    PDF »
Prevention and Induction of Autoimmune Exocrinopathy Is Dependent on Pathogenic Autoantigen Cleavage in Murine Sjogren's Syndrome.
K. Saegusa, N. Ishimaru, K. Yanagi, K. Mishima, R. Arakaki, T. Suda, I. Saito, and Y. Hayashi (2002)
J. Immunol. 169, 1050-1057
   Abstract »    Full Text »    PDF »
Autoimmune related pancreatitis.
K Okazaki and T Chiba (2002)
Gut 51, 1-4
   Abstract »    Full Text »    PDF »
Activated caspase 3 and cleaved poly(ADP-ribose)polymerase in salivary epithelium suggest a pathogenetic mechanism for Sjogren's syndrome.
F. Jimenez, S. Aiba-Masago, I. Al Hashimi, N. Vela-Roch, G. Fernandes, C.-K. Yeh, N. Talal, and H. Dang (2002)
Rheumatology 41, 338-342
   Abstract »    Full Text »    PDF »
PROGRESS IN UNDERSTANDING AUTOIMMUNE EXOCRINOPATHY USING THE NON-OBESE DIABETIC MOUSE: AN UPDATE.
S. Cha, A.B. Peck, and M.G. Humphreys-Beher (2002)
Critical Reviews in Oral Biology & Medicine 13, 5-16
   Abstract »    Full Text »    PDF »
Possible Role of Organ-Specific Autoantigen for Fas Ligand-Mediated Activation-Induced Cell Death in Murine Sjogren's Syndrome.
N. Ishimaru, K. Yanagi, K. Ogawa, T. Suda, I. Saito, and Y. Hayashi (2001)
J. Immunol. 167, 6031-6037
   Abstract »    Full Text »    PDF »
Autoantibodies to the Amino-Terminal Fragment of {beta}-Fodrin Expressed in Glandular Epithelial Cells in Patients with Sjogren's Syndrome.
M. Kuwana, T. Okano, Y. Ogawa, J. Kaburaki, and Y. Kawakami (2001)
J. Immunol. 167, 5449-5456
   Abstract »    Full Text »    PDF »
Possible Involvement of EBV-Mediated {{alpha}}-Fodrin Cleavage for Organ-Specific Autoantigen in Sjogren's Syndrome.
H. Inoue, K. Tsubota, M. Ono, Y. Kizu, F. Mizuno, K. Takada, K. Yamada, K. Yanagi, Y. Hayashi, and I. Saito (2001)
J. Immunol. 166, 5801-5809
   Abstract »    Full Text »    PDF »
Impaired Neurotransmitter Release from Lacrimal and Salivary Gland Nerves of a Murine Model of Sjogren's Syndrome.
D. Zoukhri and C. L. Kublin (2001)
Invest. Ophthalmol. Vis. Sci. 42, 925-932
   Abstract »    Full Text »
Improvement of Lacrimal Function by Topical Application of CyA in Murine Models of Sjogren's Syndrome.
K. Tsubota, H. Fujita, K. Tadano, T. Takeuchi, T. Murakami, I. Saito, and Y. Hayashi (2001)
Invest. Ophthalmol. Vis. Sci. 42, 101-110
   Abstract »    Full Text »
Autoantigen-Specific CD4+CD28low T Cell Subset Prevents Autoimmune Exocrinopathy in Murine Sjogren's Syndrome.
K. Saegusa, N. Ishimaru, K. Yanagi, N. Haneji, M. Nishino, M. Azuma, I. Saito, and Y. Hayashi (2000)
J. Immunol. 165, 2251-2257
   Abstract »    Full Text »    PDF »
Age-related Alterations in IL-1{beta}, TNF-{alpha}, and IL-6 Concentrations in Parotid Acinar Cells from BALB/c and Non-obese Diabetic Mice.
M. Yamakawa, R. Weinstein, T. Tsuji, J. McBride, D. T. W. Wong, and G. R. Login (2000)
J. Histochem. Cytochem. 48, 1033-1042
   Abstract »    Full Text »
Severe Destructive Autoimmune Lesions with Aging in Murine Sjogren's Syndrome through Fas-Mediated Apoptosis.
N. Ishimaru, T. Yoneda, K. Saegusa, K. Yanagi, N. Haneji, K. Moriyama, I. Saito, and Y. Hayashi (2000)
Am. J. Pathol. 156, 1557-1564
   Abstract »    Full Text »    PDF »
Apoptosis--new clues to the pathogenesis of Sjogren's syndrome?.
Y. I. Patel and N. J. McHugh (2000)
Rheumatology 39, 119-121
   Full Text »    PDF »
Preferential Localization of CD8+ {alpha}E{beta}7+ T Cells Around Acinar Epithelial Cells with Apoptosis in Patients with Sjogren's Syndrome.
T. Fujihara, H. Fujita, K. Tsubota, K. Saito, K. Tsuzaka, T. Abe, and T. Takeuchi (1999)
J. Immunol. 163, 2226-2235
   Abstract »    Full Text »    PDF »
Transforming Growth Factor beta Induces Caspase 3-independent Cleavage of alpha II-Spectrin (alpha -Fodrin) Coincident with Apoptosis.
T. L. Brown, S. Patil, C. D. Cianci, J. S. Morrow, and P. H. Howe (1999)
J. Biol. Chem. 274, 23256-23262
   Abstract »    Full Text »    PDF »
Estrogen Deficiency Accelerates Autoimmune Exocrinopathy in Murine Sjogren's Syndrome through Fas-Mediated Apoptosis.
N. Ishimaru, K. Saegusa, K. Yanagi, N. Haneji, I. Saito, and Y. Hayashi (1999)
Am. J. Pathol. 155, 173-181
   Abstract »    Full Text »    PDF »
Anti-{alpha}-Fodrin Antibodies in Sjogren Syndrome and Lupus Erythematosus.
T. Watanabe, T. Tsuchida, N. Kanda, K. Mori, Y. Hayashi, and K. Tamaki (1999)
Arch Dermatol 135, 535-539
   Abstract »    Full Text »    PDF »
Fas Ligand-Mediated Exocrinopathy Resembling Sjogren's Syndrome in Mice Transgenic for IL-10.
I. Saito, K. Haruta, M. Shimuta, H. Inoue, H. Sakurai, K. Yamada, N. Ishimaru, H. Higashiyama, T. Sumida, H. Ishida, et al. (1999)
J. Immunol. 162, 2488-2494
   Abstract »    Full Text »    PDF »
The 72-kDa Component of Signal Recognition Particle Is Cleaved during Apoptosis.
P. J. Utz, M. Hottelet, T. M. Le, S. J. Kim, M. E. Geiger, W. J. van Venrooij, and P. Anderson (1998)
J. Biol. Chem. 273, 35362-35370
   Abstract »    Full Text »    PDF »
Transfer of human serum IgG to nonobese diabetic Igµnull mice reveals a role for autoantibodies in the loss of secretory function of exocrine tissues in Sjogren's syndrome.
C. P. Robinson, J. Brayer, S. Yamachika, T. R. Esch, A. B. Peck, C. A. Stewart, E. Peen, R. Jonsson, and M. G. Humphreys-Beher (1998)
PNAS 95, 7538-7543
   Abstract »    Full Text »    PDF »
Association of Phosphorylated Serine/Arginine (SR) Splicing Factors With The U1-Small Ribonucleoprotein (snRNP) Autoantigen Complex Accompanies Apoptotic Cell Death.
P. J. Utz, M. Hottelet, W. J. van Venrooij, and P. Anderson (1998)
J. Exp. Med. 187, 547-560
   Abstract »    Full Text »    PDF »



To Advertise     Find Products


Science. ISSN 0036-8075 (print), 1095-9203 (online)