Enhanced Membrane Expression of the 52 KDa Ro(SS-A) and La(SS-B) Antigens by Human Keratinocytes Induced by TNF Alpha

Overview

Journal Ann Rheum Dis

Specialty Rheumatology

Date 1995 Nov 1

PMID 7492240

Citations 16

Authors

T Dorner

M Hucko

W J Mayet

U Trefzer

G R Burmester

F Hiepe

Affiliations

Soon will be listed here.

Abstract

Objective: To investigate the membrane expression of the 52 kDa Ro(SS-A) and La(SS-B) antigens in human keratinocytes under the influence of an important mediator of inflammation, TNF alpha.

Methods: Keratinocytes, isolated from human skins obtained at circumcision and identified using monoclonal antibodies, were treated with tumour necrosis factor alpha (TNF alpha) and incubated with antibodies to 52 kDa Ro(SS-A) isolated and purified from patients with systemic lupus erythematosus or Sjögren's syndrome, with mouse monoclonal antibody to La(SS-B), and (as controls) with sera from normal healthy blood donors and a mouse monoclonal antibody to U1RNP 68 kDa. Membrane expression of the 52 kDa Ro(SS-A) and La(SS-B) antigens was detected using cyto enzyme linked immunosorbent assays (ELISAs), laser scanning microscopy, and indirect immunofluorescence.

Results: After the incubation with TNF alpha, cyto ELISA revealed a significantly increased membrane binding of 52 kDa Ro(SS-A) antibodies, with a maximum after two hours, followed by enhanced 52 kDa Ro(SS-A) expression during the subsequent 24 hours. The La(SS-B) antigen was expressed rapidly after TNF alpha treatment (within one hour), with a fast decrease to the preincubation value within three hours. Indirect immunofluorescence with fixed normal human keratinocytes confirmed increased 52 kDa Ro(SS-A) and La(SS-B) antigen expression after the incubation with TNF alpha.

Conclusions: TNF alpha mediates 52 kDa Ro(SS-A) and La(SS-B) autoantigen surface expression on human keratinocytes, and may be an important factor both in antibody induction and in the initiation of immunopathogenic processes which occur after antibody binding in autoimmune dermatitis.

Citing Articles

Aged regulatory T cells fail to control autoimmune lacrimal gland pathogenic CD4 T cells.

Scholand K, Schaefer L, Govindarajan G, Yu Z, Galletti J, de Paiva C Geroscience. 2025; .

PMID: 40053297 DOI: 10.1007/s11357-025-01576-y.

Current concepts of photosensitivity in cutaneous lupus erythematosus.

Klein B, Kunz M Front Med (Lausanne). 2022; 9:939594.

PMID: 36091671 PMC: 9452788. DOI: 10.3389/fmed.2022.939594.

Molecular Mechanism of Sphingosine-1-Phosphate Receptor 1 Regulating CD4 Tissue Memory in situ T Cells in Primary Sjogren's Syndrome.

Yang X, Yang C, Wang L, Zhou Y, Yuan X, Xiang N Int J Gen Med. 2021; 14:6177-6188.

PMID: 34611431 PMC: 8485922. DOI: 10.2147/IJGM.S327304.

Immunobiology of T Cells in Sjögren's Syndrome.

Yao Y, Ma J, Chang C, Xu T, Gao C, Gershwin M Clin Rev Allergy Immunol. 2020; 60(1):111-131.

PMID: 32390096 DOI: 10.1007/s12016-020-08793-7.

Inhibition of Cathepsin S Reduces Lacrimal Gland Inflammation and Increases Tear Flow in a Mouse Model of Sjögren's Syndrome.

Klinngam W, Janga S, Lee C, Ju Y, Yarber F, Shah M Sci Rep. 2019; 9(1):9559.

PMID: 31267034 PMC: 6606642. DOI: 10.1038/s41598-019-45966-7.

References

Furukawa F, Lyons M, Norris D . Binding of antibodies to the extractable nuclear antigens SS-A/Ro and SS-B/La is induced on the surface of human keratinocytes by ultraviolet light (UVL): implications for the pathogenesis of photosensitive cutaneous lupus. J Invest Dermatol. 1990; 94(1):77-85. DOI: 10.1111/1523-1747.ep12873930. View

Baboonian C, Venables P, Booth J, Williams D, Roffe L, Maini R . Virus infection induces redistribution and membrane localization of the nuclear antigen La (SS-B): a possible mechanism for autoimmunity. Clin Exp Immunol. 1989; 78(3):454-9. PMC: 1534804. View

Prabhakar B, Allaway G, Srinivasappa J, Notkins A . Cell surface expression of the 70-kD component of Ku, a DNA-binding nuclear autoantigen. J Clin Invest. 1990; 86(4):1301-5. PMC: 296862. DOI: 10.1172/JCI114838. View

Larrick J, Wright S . Cytotoxic mechanism of tumor necrosis factor-alpha. FASEB J. 1990; 4(14):3215-23. DOI: 10.1096/fasebj.4.14.2172061. View

Frampton G, Jayne D, Perry G, Lockwood C, Cameron J . Autoantibodies to endothelial cells and neutrophil cytoplasmic antigens in systemic vasculitis. Clin Exp Immunol. 1990; 82(2):227-32. PMC: 1535114. DOI: 10.1111/j.1365-2249.1990.tb05431.x. View

Rheinwald J, Green H . Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell. 1975; 6(3):331-43. DOI: 10.1016/s0092-8674(75)80001-8. View

Lerner M, Steitz J . Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus. Proc Natl Acad Sci U S A. 1979; 76(11):5495-9. PMC: 411675. DOI: 10.1073/pnas.76.11.5495. View

Wasicek C, Reichlin M . Clinical and serological differences between systemic lupus erythematosus patients with antibodies to Ro versus patients with antibodies to Ro and La. J Clin Invest. 1982; 69(4):835-43. PMC: 370138. DOI: 10.1172/jci110523. View

Alexander E, Provost T . Cutaneous manifestations of primary Sjögren's syndrome: a reflection of vasculitis and association with anti-Ro(SSA) antibodies. J Invest Dermatol. 1983; 80(5):386-91. DOI: 10.1111/1523-1747.ep12552002. View

10.

Habets W, de Rooij D, Salden M, Verhagen A, Van Eekelen C, van de Putte L . Antibodies against distinct nuclear matrix proteins are characteristic for mixed connective tissue disease. Clin Exp Immunol. 1983; 54(1):265-76. PMC: 1536194. View

11.

Harmon C, Deng J, Peebles C, Tan E . The importance of tissue substrate in the SS-A/Ro antigen-antibody system. Arthritis Rheum. 1984; 27(2):166-73. DOI: 10.1002/art.1780270207. View

12.

Lefeber W, Norris D, Ryan S, Huff J, Lee L, Kubo M . Ultraviolet light induces binding of antibodies to selected nuclear antigens on cultured human keratinocytes. J Clin Invest. 1984; 74(4):1545-51. PMC: 425326. DOI: 10.1172/JCI111569. View

13.

Smolen J, Morimoto C, Steinberg A, Wolf A, Schlossman S, Steinberg R . Systemic lupus erythematosus: delineation of subpopulations by clinical, serologic, and T cell subset analysis. Am J Med Sci. 1985; 289(4):139-47. DOI: 10.1097/00000441-198504000-00003. View

14.

Deng J, Sontheimer R, Gilliam J . Expression of Ro/SS-A antigen in human skin and heart. J Invest Dermatol. 1985; 85(5):412-6. DOI: 10.1111/1523-1747.ep12277079. View

15.

Molina R, Provost T, Alexander E . Two types of inflammatory vascular disease in Sjögren's syndrome. Differential association with seroreactivity to rheumatoid factor and antibodies to Ro (SS-A) and with hypocomplementemia. Arthritis Rheum. 1985; 28(11):1251-8. DOI: 10.1002/art.1780281109. View

16.

Lee L, Weston W, Krueger G, Emam M, Reichlin M, Stevens J . An animal model of antibody binding in cutaneous lupus. Arthritis Rheum. 1986; 29(6):782-8. DOI: 10.1002/art.1780290612. View

17.

Rosario M, Fox O, Koren E, Harley J . Anti-Ro (SS-A) antibodies from Ro (SS-A)-immunized mice. Arthritis Rheum. 1988; 31(2):227-37. DOI: 10.1002/art.1780310211. View

18.

Hamilton R, Harley J, Bias W, Roebber M, Reichlin M, Hochberg M . Two Ro (SS-A) autoantibody responses in systemic lupus erythematosus. Correlation of HLA-DR/DQ specificities with quantitative expression of Ro (SS-A) autoantibody. Arthritis Rheum. 1988; 31(4):496-505. DOI: 10.1002/art.1780310406. View

19.

Ben-Chetrit E, Chan E, Sullivan K, Tan E . A 52-kD protein is a novel component of the SS-A/Ro antigenic particle. J Exp Med. 1988; 167(5):1560-71. PMC: 2188933. DOI: 10.1084/jem.167.5.1560. View

20.

Furukawa F, Lyons M, Lee L, Coulter S, Norris D . Estradiol enhances binding to cultured human keratinocytes of antibodies specific for SS-A/Ro and SS-B/La. Another possible mechanism for estradiol influence of lupus erythematosus. J Immunol. 1988; 141(5):1480-8. View