Logo of annrheumdAnnals of the Rheumatic DiseasesVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
Ann Rheum Dis. 1995 Nov; 54(11): 904–909.
PMCID: PMC1010041

Enhanced membrane expression of the 52 kDa Ro(SS-A) and La(SS-B) antigens by human keratinocytes induced by TNF alpha.


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.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (1.3M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Images in this article

Click on the image to see a larger version.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Wasicek CA, 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 Apr;69(4):835–843. [PMC free article] [PubMed]
  • Smolen JS, Morimoto C, Steinberg AD, Wolf A, Schlossman SF, Steinberg RT, Penner E, Reinherz E, Reichlin M, Chused TM. Systemic lupus erythematosus: delineation of subpopulations by clinical, serologic, and T cell subset analysis. Am J Med Sci. 1985 Apr;289(4):139–147. [PubMed]
  • Hamilton RG, Harley JB, Bias WB, Roebber M, Reichlin M, Hochberg MC, Arnett FC. 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 Apr;31(4):496–505. [PubMed]
  • Harley JB, Sestak AL, Willis LG, Fu SM, Hansen JA, Reichlin M. A model for disease heterogeneity in systemic lupus erythematosus. Relationships between histocompatibility antigens, autoantibodies, and lymphopenia or renal disease. Arthritis Rheum. 1989 Jul;32(7):826–836. [PubMed]
  • Mond CB, Peterson MG, Rothfield NF. Correlation of anti-Ro antibody with photosensitivity rash in systemic lupus erythematosus patients. Arthritis Rheum. 1989 Feb;32(2):202–204. [PubMed]
  • Furukawa F, Kashihara-Sawami M, Lyons MB, Norris DA. 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 Jan;94(1):77–85. [PubMed]
  • Golan TD, Elkon KB, Gharavi AE, Krueger JG. Enhanced membrane binding of autoantibodies to cultured keratinocytes of systemic lupus erythematosus patients after ultraviolet B/ultraviolet A irradiation. J Clin Invest. 1992 Sep;90(3):1067–1076. [PMC free article] [PubMed]
  • Jones SK. The effects of hormonal and other stimuli on cell-surface Ro/SSA antigen expression by human keratinocytes in vitro: their possible role in the induction of cutaneous lupus lesions. Br J Dermatol. 1992 Jun;126(6):554–560. [PubMed]
  • LeFeber WP, Norris DA, Ryan SR, Huff JC, Lee LA, Kubo M, Boyce ST, Kotzin BL, Weston WL. Ultraviolet light induces binding of antibodies to selected nuclear antigens on cultured human keratinocytes. J Clin Invest. 1984 Oct;74(4):1545–1551. [PMC free article] [PubMed]
  • Casciola-Rosen LA, Anhalt G, Rosen A. Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes. J Exp Med. 1994 Apr 1;179(4):1317–1330. [PMC free article] [PubMed]
  • Furukawa F, Lyons MB, Lee LA, Coulter SN, Norris DA. 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 Sep 1;141(5):1480–1488. [PubMed]
  • Baboonian C, Venables PJ, Booth J, Williams DG, Roffe LM, Maini RN. Virus infection induces redistribution and membrane localization of the nuclear antigen La (SS-B): a possible mechanism for autoimmunity. Clin Exp Immunol. 1989 Dec;78(3):454–459. [PMC free article] [PubMed]
  • Mayet WJ, Csernok E, Szymkowiak C, Gross WL, Meyer zum Büschenfelde KH. Human endothelial cells express proteinase 3, the target antigen of anticytoplasmic antibodies in Wegener's granulomatosis. Blood. 1993 Aug 15;82(4):1221–1229. [PubMed]
  • Kato T, Sasakawa H, Suzuki S, Shirako M, Tashiro F, Nishioka K, Yamamoto K. Autoepitopes of the 52-kd SS-A/Ro molecule. Arthritis Rheum. 1995 Jul;38(7):990–998. [PubMed]
  • Chan EK, Hamel JC, Buyon JP, Tan EM. Molecular definition and sequence motifs of the 52-kD component of human SS-A/Ro autoantigen. J Clin Invest. 1991 Jan;87(1):68–76. [PMC free article] [PubMed]
  • Rheinwald JG, Green H. Serial cultivation of strains of human epidermal keratinocytes: the formation of keratinizing colonies from single cells. Cell. 1975 Nov;6(3):331–343. [PubMed]
  • Frampton G, Jayne DR, Perry GJ, Lockwood CM, Cameron JS. Autoantibodies to endothelial cells and neutrophil cytoplasmic antigens in systemic vasculitis. Clin Exp Immunol. 1990 Nov;82(2):227–232. [PMC free article] [PubMed]
  • Habets WJ, de Rooij DJ, Salden MH, Verhagen AP, van Eekelen CA, van de Putte LB, van Venrooij WJ. Antibodies against distinct nuclear matrix proteins are characteristic for mixed connective tissue disease. Clin Exp Immunol. 1983 Oct;54(1):265–276. [PMC free article] [PubMed]
  • Deng JS, Sontheimer RD, Gilliam JN. Expression of Ro/SS-A antigen in human skin and heart. J Invest Dermatol. 1985 Nov;85(5):412–416. [PubMed]
  • Ben-Chetrit E, Chan EK, Sullivan KF, Tan EM. A 52-kD protein is a novel component of the SS-A/Ro antigenic particle. J Exp Med. 1988 May 1;167(5):1560–1571. [PMC free article] [PubMed]
  • Harmon CE, Deng JS, Peebles CL, Tan EM. The importance of tissue substrate in the SS-A/Ro antigen-antibody system. Arthritis Rheum. 1984 Feb;27(2):166–173. [PubMed]
  • Rosario MO, Fox OF, Koren E, Harley JB. Anti-Ro (SS-A) antibodies from Ro (SS-A)-immunized mice. Arthritis Rheum. 1988 Feb;31(2):227–237. [PubMed]
  • Lerner MR, Steitz JA. Antibodies to small nuclear RNAs complexed with proteins are produced by patients with systemic lupus erythematosus. Proc Natl Acad Sci U S A. 1979 Nov;76(11):5495–5499. [PMC free article] [PubMed]
  • Slobbe RL, Pluk W, van Venrooij WJ, Pruijn GJ. Ro ribonucleoprotein assembly in vitro. Identification of RNA-protein and protein-protein interactions. J Mol Biol. 1992 Sep 20;227(2):361–366. [PubMed]
  • Bachmann M, Zaubitzer T, Müller WE. The autoantigen La/SSB: detection on and uptake by mitotic cells. Exp Cell Res. 1992 Aug;201(2):387–398. [PubMed]
  • Rieber M, Urbina C, Rieber MS. DNA on membrane receptors: a target for monoclonal anti-DNA antibody induced by a nucleoprotein shed in systemic lupus erythematosus. Biochem Biophys Res Commun. 1989 Mar 31;159(3):1441–1447. [PubMed]
  • Mécheri S, Dannecker G, Dennig D, Poncet P, Hoffmann MK. Anti-histone autoantibodies react specifically with the B cell surface. Mol Immunol. 1993 Apr;30(6):549–557. [PubMed]
  • Prabhakar BS, Allaway GP, Srinivasappa J, Notkins AL. Cell surface expression of the 70-kD component of Ku, a DNA-binding nuclear autoantigen. J Clin Invest. 1990 Oct;86(4):1301–1305. [PMC free article] [PubMed]
  • Casciola-Rosen LA, Miller DK, Anhalt GJ, Rosen A. Specific cleavage of the 70-kDa protein component of the U1 small nuclear ribonucleoprotein is a characteristic biochemical feature of apoptotic cell death. J Biol Chem. 1994 Dec 9;269(49):30757–30760. [PubMed]
  • Grell M, Zimmermann G, Hülser D, Pfizenmaier K, Scheurich P. TNF receptors TR60 and TR80 can mediate apoptosis via induction of distinct signal pathways. J Immunol. 1994 Sep 1;153(5):1963–1972. [PubMed]
  • Robaye B, Mosselmans R, Fiers W, Dumont JE, Galand P. Tumor necrosis factor induces apoptosis (programmed cell death) in normal endothelial cells in vitro. Am J Pathol. 1991 Feb;138(2):447–453. [PMC free article] [PubMed]
  • Larrick JW, Wright SC. Cytotoxic mechanism of tumor necrosis factor-alpha. FASEB J. 1990 Nov;4(14):3215–3223. [PubMed]
  • Trefzer U, Brockhaus M, Lötscher H, Parlow F, Budnik A, Grewe M, Christoph H, Kapp A, Schöpf E, Luger TA, et al. The 55-kD tumor necrosis factor receptor on human keratinocytes is regulated by tumor necrosis factor-alpha and by ultraviolet B radiation. J Clin Invest. 1993 Jul;92(1):462–470. [PMC free article] [PubMed]
  • Lee LA, Weston WL, Krueger GG, Emam M, Reichlin M, Stevens JO, Surbrugg SK, Vasil A, Norris DA. An animal model of antibody binding in cutaneous lupus. Arthritis Rheum. 1986 Jun;29(6):782–788. [PubMed]
  • Molina R, Provost TT, Alexander EL. 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 Nov;28(11):1251–1258. [PubMed]
  • Alexander EL, Provost TT. Cutaneous manifestations of primary Sjögren's syndrome: a reflection of vasculitis and association with anti-Ro(SSA) antibodies. J Invest Dermatol. 1983 May;80(5):386–391. [PubMed]

Articles from Annals of the Rheumatic Diseases are provided here courtesy of BMJ Group


Save items

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • PubMed
    PubMed citations for these articles
  • Substance
    PubChem chemical substance records that cite the current articles. These references are taken from those provided on submitted PubChem chemical substance records.

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...