Autoantibodies to the Heat-shock Protein Hsp90 in Systemic Lupus Erythematosus

Overview

Journal J Clin Invest

Specialty General Medicine

Date 1988 Jan 1

PMID 3335628

Citations 34

Authors

S Minota

S Koyasu

I YAHARA

J Winfield

Affiliations

Soon will be listed here.

Abstract

Patients with systemic lupus erythematosus (SLE) develop multiple autoantibodies to self-antigens. Analysis of autoantibody systems in this and related autoimmune disorders can provide information of etiologic and pathogenetic significance. We report here a previously unrecognized autoantibody to the 90,000-D heat-shock protein, hsp90, a molecule thought to have important functions in the cellular response to stress, virus-induced transformation, steroid hormone receptor action, and cellular activation. Autoantibodies to hsp90 were exclusively of the IgG class, and were detected in approximately 50% of unselected patients with SLE and 2/6 patients with idiopathic polymyositis. Anti-hsp90 antibodies were not detected in sera from 10 normal subjects, 10 patients with rheumatoid arthritis, or 7 patients with scleroderma. The identity of this major intracytoplasmic antigen was established by its specific removal from nonionic detergent cell lysates following immunoabsorption with monospecific rabbit anti-hsp90, and by demonstration of increased synthesis following a 10-min 45 degrees C heat shock. These data define the frequent occurrence of a novel autoantibody to a major heat-shock protein in patients with SLE.

Citing Articles

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The role of lysosomes in metabolic and autoimmune diseases.

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Heat Shock Protein 90 (Hsp90) and Hsp70 as Potential Therapeutic Targets in Autoimmune Skin Diseases.

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Untangling COVID-19 and autoimmunity: Identification of plausible targets suggests multi organ involvement.

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Focal adhesion ribonucleoprotein complex proteins are major humoral cancer antigens and targets in autoimmune diseases.

Atsumi S, Katoh H, Komura D, Hashimoto I, Furuya G, Koda H Commun Biol. 2020; 3(1):588.

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References

Shapiro A, Vinuela E, Maizel Jr J . Molecular weight estimation of polypeptide chains by electrophoresis in SDS-polyacrylamide gels. Biochem Biophys Res Commun. 1967; 28(5):815-20. DOI: 10.1016/0006-291x(67)90391-9. View

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

Dickler H . Studies of the human lymphocyte receptor for heat-aggregated or antigen-complexed immunoglobulin. J Exp Med. 1974; 140(2):508-22. PMC: 2139583. DOI: 10.1084/jem.140.2.508. View

Jasin H, ZIFF M . Immunoglobulin synthesis by peripheral blood cells in systemic lupus erythematosus. Arthritis Rheum. 1975; 18(3):219-28. DOI: 10.1002/art.1780180305. View

Cadman E, Bostwick J, EICHBERG J . Determination of protein by a modified Lowry procedure in the presence of some commonly used detergents. Anal Biochem. 1979; 96(1):21-3. DOI: 10.1016/0003-2697(79)90548-7. View

Towbin H, Staehelin T, Gordon J . Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A. 1979; 76(9):4350-4. PMC: 411572. DOI: 10.1073/pnas.76.9.4350. View

Yu D, Winchester R, Fu S, Gibofsky A, Ko H, KUNKEL H . Peripheral blood Ia-positive T cells. Increases in certain diseases and after immunization. J Exp Med. 1980; 151(1):91-100. PMC: 2185766. DOI: 10.1084/jem.151.1.91. View

Oppermann H, Levinson W, Bishop J . A cellular protein that associates with the transforming protein of Rous sarcoma virus is also a heat-shock protein. Proc Natl Acad Sci U S A. 1981; 78(2):1067-71. PMC: 319947. DOI: 10.1073/pnas.78.2.1067. View

Okudaira K, Searles R, Tanimoto K, Horiuchi Y, Williams Jr R . T lymphocyte interaction with immunoglobulin G antibody in systemic lupus erythematosus. J Clin Invest. 1982; 69(4):1026-38. PMC: 370158. DOI: 10.1172/jci110506. View

10.

Adkins B, Hunter T, Sefton B . The transforming proteins of PRCII virus and Rous sarcoma virus form a complex with the same two cellular phosphoproteins. J Virol. 1982; 43(2):448-55. PMC: 256147. DOI: 10.1128/JVI.43.2.448-455.1982. View

11.

Tan E . Autoantibodies to nuclear antigens (ANA): their immunobiology and medicine. Adv Immunol. 1982; 33:167-240. DOI: 10.1016/s0065-2776(08)60836-6. View

12.

Tan E, Cohen A, Fries J, MASI A, McShane D, Rothfield N . The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982; 25(11):1271-7. DOI: 10.1002/art.1780251101. View

13.

Kammer G . Impaired T cell capping and receptor regeneration in active systemic lupus erythematosus. Evidence for a disorder intrinsic to the T lymphocyte. J Clin Invest. 1983; 72(5):1686-97. PMC: 370457. DOI: 10.1172/JCI111128. View

14.

Morimoto C, Reinherz E, Distaso J, Steinberg A, Schlossman S . Relationship between systemic lupus erythematosus T cell subsets, anti-T cell antibodies, and T cell functions. J Clin Invest. 1984; 73(3):689-700. PMC: 425070. DOI: 10.1172/JCI111261. View

15.

Iida H, YAHARA I . Durable synthesis of high molecular weight heat shock proteins in G0 cells of the yeast and other eucaryotes. J Cell Biol. 1984; 99(1 Pt 1):199-207. PMC: 2275615. DOI: 10.1083/jcb.99.1.199. View

16.

Schuh S, Yonemoto W, Brugge J, Bauer V, Riehl R, SULLIVAN W . A 90,000-dalton binding protein common to both steroid receptors and the Rous sarcoma virus transforming protein, pp60v-src. J Biol Chem. 1985; 260(26):14292-6. View

17.

Winfield J . Anti-lymphocyte antibodies in systemic lupus erythematosus. Clin Rheum Dis. 1985; 11(3):523-49. View

18.

Srinivasappa J, Saegusa J, Prabhakar B, Gentry M, Buchmeier M, WIKTOR T . Molecular mimicry: frequency of reactivity of monoclonal antiviral antibodies with normal tissues. J Virol. 1986; 57(1):397-401. PMC: 252745. DOI: 10.1128/JVI.57.1.397-401.1986. View

19.

Koyasu S, Nishida E, Kadowaki T, Matsuzaki F, Iida K, Harada F . Two mammalian heat shock proteins, HSP90 and HSP100, are actin-binding proteins. Proc Natl Acad Sci U S A. 1986; 83(21):8054-8. PMC: 386865. DOI: 10.1073/pnas.83.21.8054. View

20.

Nishida E, Koyasu S, Sakai H, YAHARA I . Calmodulin-regulated binding of the 90-kDa heat shock protein to actin filaments. J Biol Chem. 1986; 261(34):16033-6. View