• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Jun 1995; 95(6): 2672–2679.
PMCID: PMC295950

The antiperinuclear factor and the so-called antikeratin antibodies are the same rheumatoid arthritis-specific autoantibodies.

Abstract

The so-called antikeratin antibodies (AKA) and the antiperinuclear factor (APF) are the most specific serological markers of RA. Using indirect immunofluorescence, AKA label the stratum corneum of various cornified epithelia and APF the keratohyalin granules of human buccal mucosa epithelium. We recently demonstrated that AKA recognize human epidermal filaggrin. Here, we report the identification of the major APF antigen as a diffuse protein band of 200-400 kD. This protein is seen to be closely related to human epidermal (pro) filaggrin since it was recognized by four antifilaggrin mAbs specific for different epitopes, and since the APF titers of RA sera were found to be correlated to their AKA titers and to their immunoblotting reactivities to filaggrin. Immunoabsorption of RA sera on purified epidermal filaggrin abolished their reactivities to the granules of buccal epithelial cells and to the 200-400-kD antigen. Moreover, antifilaggrin autoantibodies, i.e., AKA, affinity purified from RA sera, were shown to immunodetect the 200-400-kD antigen and to stain these granules. These results indicate that AKA and APF are largely the same autoantibodies. They recognize human epidermal filaggrin and (pro) filaggrin-related proteins of buccal epithelial cells. Identification of the epitopes recognized by these autoantibodies, which we propose to name antifilaggrin autoantibodies, will certainly open new paths of research into the pathophysiology of RA.

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 (2.2M), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Terato K, Shimozuru Y, Katayama K, Takemitsu Y, Yamashita I, Miyatsu M, Fujii K, Sagara M, Kobayashi S, Goto M, et al. Specificity of antibodies to type II collagen in rheumatoid arthritis. Arthritis Rheum. 1990 Oct;33(10):1493–1500. [PubMed]
  • Steiner G, Hartmuth K, Skriner K, Maurer-Fogy I, Sinski A, Thalmann E, Hassfeld W, Barta A, Smolen JS. Purification and partial sequencing of the nuclear autoantigen RA33 shows that it is indistinguishable from the A2 protein of the heterogeneous nuclear ribonucleoprotein complex. J Clin Invest. 1992 Sep;90(3):1061–1066. [PMC free article] [PubMed]
  • Tuaillon N, Muller S, Pasquali JL, Bordigoni P, Youinou P, Van Regenmortel MH. Antibodies from patients with rheumatoid arthritis and juvenile chronic arthritis analyzed with core histone synthetic peptides. Int Arch Allergy Appl Immunol. 1990;91(3):297–305. [PubMed]
  • Senécal JL, Oliver JM, Rothfield N. Anticytoskeletal autoantibodies in the connective tissue diseases. Arthritis Rheum. 1985 Aug;28(8):889–898. [PubMed]
  • NIENHUIS RL, MANDEMA E. A NEW SERUM FACTOR IN PATIENTS WITH RHEUMATOID ARTHRITIS; THE ANTIPERINUCLEAR FACTOR. Ann Rheum Dis. 1964 Jul;23:302–305. [PMC free article] [PubMed]
  • Sondag-Tschroots IR, Aaij C, Smit JW, Feltkamp TE. The antiperinuclear factor. 1. The diagnostic significance of the antiperinuclear factor for rheumatoid arthritis. Ann Rheum Dis. 1979 Jun;38(3):248–251. [PMC free article] [PubMed]
  • Smit JW, Sondag-Tschroots IR, Aaij C, Feltkamp TE, Feltkamp-Vroom TM. The antiperinuclear factor: II. A light microscopical and immunofluorescence study on the antigenic substrate. Ann Rheum Dis. 1980 Aug;39(4):381–386. [PMC free article] [PubMed]
  • Johnson GD, Carvalho A, Holborow EJ, Goddard DH, Russell G. Antiperinuclear factor and keratin antibodies in rheumatoid arthritis. Ann Rheum Dis. 1981 Jun;40(3):263–266. [PMC free article] [PubMed]
  • Scherbaum WA, Youinou PY, Le Goff P, Bottazzo GF. Anti-perinuclear and rheumatoid factor in different forms of autoimmune thyroid disease. Clin Exp Immunol. 1984 Mar;55(3):516–518. [PMC free article] [PubMed]
  • Kataaha PK, Mortazavi-Milani SM, Russell G, Holborow EJ. Anti-intermediate filament antibodies, antikeratin antibody, and antiperinuclear factor in rheumatoid arthritis and infectious mononucleosis. Ann Rheum Dis. 1985 Jul;44(7):446–449. [PMC free article] [PubMed]
  • Westgeest AA, Boerbooms AM, Jongmans M, Vandenbroucke JP, Vierwinden G, van de Putte LB. Antiperinuclear factor: indicator of more severe disease in seronegative rheumatoid arthritis. J Rheumatol. 1987 Oct;14(5):893–897. [PubMed]
  • Janssens X, Veys EM, Verbruggen G, Declercq L. The diagnostic significance of the antiperinuclear factor for rheumatoid arthritis. J Rheumatol. 1988 Sep;15(9):1346–1350. [PubMed]
  • Boerbooms AM, Westgeest AA, Reekers P, van de Putte LB. Immunogenetic heterogeneity of seronegative rheumatoid arthritis and the antiperinuclear factor. Ann Rheum Dis. 1990 Jan;49(1):15–17. [PMC free article] [PubMed]
  • Vivino FB, Maul GG. Histologic and electron microscopic characterization of the antiperinuclear factor antigen. Arthritis Rheum. 1990 Jul;33(7):960–969. [PubMed]
  • Youinou P, Le Goff P, Dumay A, Lelong A, Fauquert P, Jouquan J. The antiperinuclear factor. I. Clinical and serologic associations. Clin Exp Rheumatol. 1990 May-Jun;8(3):259–264. [PubMed]
  • Hoet RM, Boerbooms AM, Arends M, Ruiter DJ, van Venrooij WJ. Antiperinuclear factor, a marker autoantibody for rheumatoid arthritis: colocalisation of the perinuclear factor and profilaggrin. Ann Rheum Dis. 1991 Sep;50(9):611–618. [PMC free article] [PubMed]
  • Hoet RM, Voorsmit RA, Van Venrooij WJ. The perinuclear factor, a rheumatoid arthritis-specific autoantigen, is not present in keratohyalin granules of cultured buccal mucosa cells. Clin Exp Immunol. 1991 Apr;84(1):59–65. [PMC free article] [PubMed]
  • Aho K, von Essen R, Kurki P, Palosuo T, Heliövaara M. Antikeratin antibody and antiperinuclear factor as markers for subclinical rheumatoid disease process. J Rheumatol. 1993 Aug;20(8):1278–1281. [PubMed]
  • von Essen R, Kurki P, Isomäki H, Okubo S, Kautiainen H, Aho K. Prospect for an additional laboratory criterion for rheumatoid arthritis. Scand J Rheumatol. 1993;22(6):267–272. [PubMed]
  • Young BJ, Mallya RK, Leslie RD, Clark CJ, Hamblin TJ. Anti-keratin antibodies in rheumatoid arthritis. Br Med J. 1979 Jul 14;2(6182):97–99. [PMC free article] [PubMed]
  • Quismorio FP, Jr, Kaufman RL, Beardmore T, Mongan ES. Reactivity of serum antibodies to the keratin layer of rat esophagus in patients with rheumatoid arthritis. Arthritis Rheum. 1983 Apr;26(4):494–499. [PubMed]
  • Mallya RK, Young BJ, Pepys MB, Hamblin TJ, Mace BE, Hamilton EB. Anti-keratin antibodies in rheumatoid arthritis: frequency and correlation with other features of the disease. Clin Exp Immunol. 1983 Jan;51(1):17–20. [PMC free article] [PubMed]
  • Ordeig J, Guardia J. Diagnostic value of antikeratin antibodies in rheumatoid arthritis. J Rheumatol. 1984 Oct;11(5):602–604. [PubMed]
  • Hajiroussou VJ, Skingle J, Gillett AP, Webley M. Significance of antikeratin antibodies in rheumatoid arthritis. J Rheumatol. 1985 Feb;12(1):57–59. [PubMed]
  • Youinou P, Le Goff P, Colaco CB, Thivolet J, Tater D, Viac J, Shipley M. Antikeratin antibodies in serum and synovial fluid show specificity for rheumatoid arthritis in a study of connective tissue diseases. Ann Rheum Dis. 1985 Jul;44(7):450–454. [PMC free article] [PubMed]
  • Kirstein H, Mathiesen FK. Antikeratin antibodies in rheumatoid arthritis. Methods and clinical significance. Scand J Rheumatol. 1987;16(5):331–338. [PubMed]
  • Vincent C, Serre G, Lapeyre F, Fournié B, Ayrolles C, Fournié A, Soleilhavoup JP. High diagnostic value in rheumatoid arthritis of antibodies to the stratum corneum of rat oesophagus epithelium, so-called 'antikeratin antibodies'. Ann Rheum Dis. 1989 Sep;48(9):712–722. [PMC free article] [PubMed]
  • Kirstein H, Hjarvard K, Hansen TM. Antikeratin antibodies in synovial fluid in rheumatoid arthritis. APMIS. 1989 Feb;97(2):185–189. [PubMed]
  • Vincent C, Serre G, Basile JP, Lestra HC, Girbal E, Sebbag M, Soleilhavoup JP. Subclass distribution of IgG antibodies to the rat oesophagus stratum corneum (so-called anti-keratin antibodies) in rheumatoid arthritis. Clin Exp Immunol. 1990 Jul;81(1):83–89. [PMC free article] [PubMed]
  • Vincent C, Serre G, Fournié B, Fournié A, Soleilhavoup JP. Natural IgG to epidermal cytokeratins vs IgG to the stratum corneum of the rat oesophagus epithelium, so-called 'antikeratin antibodies', in rheumatoid arthritis and other rheumatic diseases. J Autoimmun. 1991 Jun;4(3):493–505. [PubMed]
  • Kurki P, Aho K, Palosuo T, Heliövaara M. Immunopathology of rheumatoid arthritis. Antikeratin antibodies precede the clinical disease. Arthritis Rheum. 1992 Aug;35(8):914–917. [PubMed]
  • Paimela L, Gripenberg M, Kurki P, Leirisalo-Repo M. Antikeratin antibodies: diagnostic and prognostic markers for early rheumatoid arthritis. Ann Rheum Dis. 1992 Jun;51(6):743–746. [PMC free article] [PubMed]
  • Girbal E, Sebbag M, Gomès-Daudrix V, Simon M, Vincent C, Serre G. Characterisation of the rat oesophagus epithelium antigens defined by the so-called 'antikeratin antibodies', specific for rheumatoid arthritis. Ann Rheum Dis. 1993 Oct;52(10):749–757. [PMC free article] [PubMed]
  • Simon M, Girbal E, Sebbag M, Gomès-Daudrix V, Vincent C, Salama G, Serre G. The cytokeratin filament-aggregating protein filaggrin is the target of the so-called "antikeratin antibodies," autoantibodies specific for rheumatoid arthritis. J Clin Invest. 1993 Sep;92(3):1387–1393. [PMC free article] [PubMed]
  • Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988 Mar;31(3):315–324. [PubMed]
  • Dale BA, Gown AM, Fleckman P, Kimball JR, Resing KA. Characterization of two monoclonal antibodies to human epidermal keratohyalin: reactivity with filaggrin and related proteins. J Invest Dermatol. 1987 Mar;88(3):306–313. [PubMed]
  • van Muijen GN, Ruiter DJ, Franke WW, Achtstätter T, Haasnoot WH, Ponec M, Warnaar SO. Cell type heterogeneity of cytokeratin expression in complex epithelia and carcinomas as demonstrated by monoclonal antibodies specific for cytokeratins nos. 4 and 13. Exp Cell Res. 1986 Jan;162(1):97–113. [PubMed]
  • Gomès-Daudrix V, Sebbag M, Girbal E, Vincent C, Simon M, Rakotoarivony J, Abbal M, Fournié B, Serre G. Immunoblotting detection of so-called 'antikeratin antibodies': a new assay for the diagnosis of rheumatoid arthritis. Ann Rheum Dis. 1994 Nov;53(11):735–742. [PMC free article] [PubMed]
  • Simon M, Vincent C, Haftek M, Girbal E, Sebbag M, Gomès-Daudrix V, Serre G. The rheumatoid arthritis-associated autoantibodies to filaggrin label the fibrous matrix of the cornified cells but not the profilaggrin-containing keratohyalin granules in human epidermis. Clin Exp Immunol. 1995 Apr;100(1):90–98. [PMC free article] [PubMed]
  • Smith SA, Dale BA. Immunologic localization of filaggrin in human oral epithelia and correlation with keratinization. J Invest Dermatol. 1986 Feb;86(2):168–172. [PubMed]
  • Chan KW, Felson DT, Yood RA, Walker AM. The lag time between onset of symptoms and diagnosis of rheumatoid arthritis. Arthritis Rheum. 1994 Jun;37(6):814–820. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

Formats:

Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...

Links

  • MedGen
    MedGen
    Related information in MedGen
  • PubMed
    PubMed
    PubMed citations for these articles
  • Substance
    Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...