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Ann Rheum Dis. 1991 Sep; 50(9): 611–618.
PMCID: PMC1004503

Antiperinuclear factor, a marker autoantibody for rheumatoid arthritis: colocalisation of the perinuclear factor and profilaggrin.


The antiperinuclear factor, an autoantibody specific for rheumatoid arthritis, was found in 51/63 (81%) patients with rheumatoid arthritis by indirect immunofluorescence on human buccal mucosa cells. The sensitivity of the antiperinuclear factor test was increased by pretreating the buccal mucosa cells with 0.5% Triton-X100. The specificity of the test for rheumatoid arthritis as compared with control serum samples was maintained. The localisation of the perinuclear factor in the keratohyalin granules of the buccal mucosa cells was verified by immunoelectron microscopy. The perinuclear factor was found to be an insoluble protein whose antigenicity was sensitive to various fixation procedures. In serum samples from patients with rheumatoid arthritis there was a positive correlation between the presence of antiperinuclear factor and the presence of the so called antikeratin antibodies as detected by immunofluorescence on unfixed rat oesophagus cryostat sections. No relation was found between the presence of the perinuclear factor and either the rheumatoid factor, Epstein-Barr virus components, or any cytokeratin. By double immunofluorescence an exact colocalisation of the perinuclear factor and profilaggrin was found. Although the precise biochemical identity of the perinuclear factor remains unclear, our results suggest that it is a protein only present in the fully differentiated squamous epithelial cell layer.

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  • Tan EM. Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol. 1989;44:93–151. [PubMed]
  • Kurki P, Helve T, Virtanen I. Antibodies to cytoplasmic intermediate filaments in rheumatic diseases. J Rheumatol. 1983 Aug;10(4):558–562. [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]
  • Senecal JL, Rothfield NF, Oliver JM. Immunoglobulin M autoantibody to vimentin intermediate filaments. J Clin Invest. 1982 Mar;69(3):716–721. [PMC free article] [PubMed]
  • Kurki P, Virtanen I. The detection of human antibodies against cytoskeletal components. J Immunol Methods. 1984 Mar 16;67(2):209–223. [PubMed]
  • Osung OA, Chandra M, Holborow EJ. Intermediate filaments in synovial lining cells in rheumatoid arthritis and other arthritides are of vimentin type. Ann Rheum Dis. 1982 Feb;41(1):74–77. [PMC free article] [PubMed]
  • Toh BH, Yildiz A, Sotelo J, Osung O, Holborow EJ, Kanakoudi F, Small JV. Viral infections and IgM autoantibodies to cytoplasmic intermediate filaments. Clin Exp Immunol. 1979 Jul;37(1):76–82. [PMC free article] [PubMed]
  • Alcover A, Molano J, Renart J, Gil-Aguado A, Nieto A, Avila J. Antibodies to vimentin intermediate filaments in sera from patients with systemic lupus erythematosus. Arthritis Rheum. 1984 Aug;27(8):922–928. [PubMed]
  • Osung OA, Chandra M, Holborow EJ. Antibody to intermediate filaments of the cytoskeleton. Ann Rheum Dis. 1982 Feb;41(1):69–73. [PMC free article] [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]
  • Kirstein H, Mathiesen FK. Antikeratin antibodies in rheumatoid arthritis. Methods and clinical significance. Scand J Rheumatol. 1987;16(5):331–338. [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]
  • Scott DL, Delamere JP, Jones LJ, Walton KW. Significance of laminar antikeratin antibodies to rat oesophagus in rheumatoid arthritis. Ann Rheum Dis. 1981 Jun;40(3):267–271. [PMC free article] [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]
  • 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]
  • 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]
  • 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]
  • Youinou P, Pennec Y, Le Goff P, Ferec C, Morrow WJ, Le Menn G. Antiperinuclear factor in Sjögren's syndrome in the presence or absence of rheumatoid arthritis. Clin Exp Rheumatol. 1984 Jan-Mar;2(1):5–9. [PubMed]
  • Youinou P, Zabbe C, Eveillaud C, Dewitte JD, Kerbourc'h JF, Ferec C, Clavier J. Antiperinuclear activity in lung carcinoma patients. Cancer Immunol Immunother. 1984;18(2):80–81. [PubMed]
  • Youinou P, Le Goff P, Miossec P, Moineau MP, Ferec C. Untersuchungen zur Beziehung zwischen anti-perinukleären Faktoren, Anti-Keratin-Antikörpern und dem agglutinierenden und nichtagglutinierenden Rheumafaktor bei der chronischen Polyarthritis. Z Rheumatol. 1983 Jan-Feb;42(1):36–39. [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]
  • 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]
  • Youinou P, Le Goff P, Casburn-Budd R, Ferec C, Pennec Y. Evidence for relationships between antiperinuclear and IgG rheumatoid factor. Rheumatol Int. 1984;4(3):111–114. [PubMed]
  • de Rooij DJ, van de Putte LB, Habets WJ, Verbeek AL, van Venrooij WJ. The use of immunoblotting to detect antibodies to nuclear and cytoplasmic antigens. Clinical and serological associations in rheumatic diseases. Scand J Rheumatol. 1988;17(5):353–364. [PubMed]
  • Ramaekers F, Huysmans A, Moesker O, Kant A, Jap P, Herman C, Vooijs P. Monoclonal antibody to keratin filaments, specific for glandular epithelia and their tumors. Use in surgical pathology. Lab Invest. 1983 Sep;49(3):353–361. [PubMed]
  • Ramaekers FC, Puts JJ, Moesker O, Kant A, Huysmans A, Haag D, Jap PH, Herman CJ, Vooijs GP. Antibodies to intermediate filament proteins in the immunohistochemical identification of human tumours: an overview. Histochem J. 1983 Jul;15(7):691–713. [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]
  • Burke B, Tooze J, Warren G. A monoclonal antibody which recognises each of the nuclear lamin polypeptides in mammalian cells. EMBO J. 1983;2(3):361–367. [PMC free article] [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]
  • Murozuka T, Fukuyama K, Epstein WL. Immunochemical comparison of histidine-rich protein in keratohyalin granules and cornified cells. Biochim Biophys Acta. 1979 Aug 28;579(2):334–345. [PubMed]
  • Kim HJ, Bernstein IA. Exposure to 12-O-tetradecanoylphorbol-13-acetate (TPA) induces the synthesis of histidine-rich protein (filaggrin) in monolayer cultures of rat keratinocytes. J Invest Dermatol. 1987 May;88(5):624–629. [PubMed]
  • Woodcock-Mitchell J, Eichner R, Nelson WG, Sun TT. Immunolocalization of keratin polypeptides in human epidermis using monoclonal antibodies. J Cell Biol. 1982 Nov;95(2 Pt 1):580–588. [PMC free article] [PubMed]
  • Lazarides E. Intermediate filaments: a chemically heterogeneous, developmentally regulated class of proteins. Annu Rev Biochem. 1982;51:219–250. [PubMed]
  • Billings PB, Allen RW, Jensen FC, Hoch SO. Anti-RNP monoclonal antibodies derived from a mouse strain with lupus-like autoimmunity. J Immunol. 1982 Mar;128(3):1176–1180. [PubMed]
  • Lerner EA, Lerner MR, Janeway CA, Jr, Steitz JA. Monoclonal antibodies to nucleic acid-containing cellular constituents: probes for molecular biology and autoimmune disease. Proc Natl Acad Sci U S A. 1981 May;78(5):2737–2741. [PMC free article] [PubMed]
  • Habets WJ, Hoet MH, De Jong BA, Van der Kemp A, Van Venrooij WJ. Mapping of B cell epitopes on small nuclear ribonucleoproteins that react with human autoantibodies as well as with experimentally-induced mouse monoclonal antibodies. J Immunol. 1989 Oct 15;143(8):2560–2566. [PubMed]
  • Klein F, Bronsveld W, Norde W, Van Romunde LK, Singer JM. A modified latex-fixation test for the detection of rheumatoid factors. J Clin Pathol. 1979 Jan;32(1):90–92. [PMC free article] [PubMed]
  • Fleckman P, Dale BA, Holbrook KA. Profilaggrin, a high-molecular-weight precursor of filaggrin in human epidermis and cultured keratinocytes. J Invest Dermatol. 1985 Dec;85(6):507–512. [PubMed]
  • Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. [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]
  • Habets WJ, de Rooij DJ, Hoet MH, van de Putte LB, van Venrooij WJ. Quantitation of anti-RNP and anti-Sm antibodies in MCTD and SLE patients by immunoblotting. Clin Exp Immunol. 1985 Feb;59(2):457–466. [PMC free article] [PubMed]
  • Ruiter DJ, Mauw BJ, Beyer-Boon ME. Ultrastructure of normal epithelial cells in Papanicolaou-stained cervical smears. An application of a modified open-face embedding technique for transmission electron microscopy. Acta Cytol. 1979 Nov-Dec;23(6):507–515. [PubMed]
  • Miossec P, Youinou P, Le Goff P, Moineau MP. Clinical relevance of antikeratin antibodies in rheumatoid arthritis. Clin Rheumatol. 1982 Sep;1(3):185–189. [PubMed]
  • Dale BA, Holbrook KA, Kimball JR, Hoff M, Sun TT. Expression of epidermal keratins and filaggrin during human fetal skin development. J Cell Biol. 1985 Oct;101(4):1257–1269. [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]

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