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Annals of the Rheumatic Diseases logoLink to Annals of the Rheumatic Diseases
. 1991 Sep;50(9):611–618. doi: 10.1136/ard.50.9.611

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

R M Hoet 1, A M Boerbooms 1, M Arends 1, D J Ruiter 1, W J van Venrooij 1
PMCID: PMC1004503  PMID: 1718228

Abstract

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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Selected References

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  1. 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. doi: 10.1002/art.1780270812. [DOI] [PubMed] [Google Scholar]
  2. Billings P. B., Allen R. W., Jensen F. C., Hoch S. O. Anti-RNP monoclonal antibodies derived from a mouse strain with lupus-like autoimmunity. J Immunol. 1982 Mar;128(3):1176–1180. [PubMed] [Google Scholar]
  3. 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. doi: 10.1002/j.1460-2075.1983.tb01431.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dale B. A., Gown A. M., Fleckman P., Kimball J. R., Resing K. A. Characterization of two monoclonal antibodies to human epidermal keratohyalin: reactivity with filaggrin and related proteins. J Invest Dermatol. 1987 Mar;88(3):306–313. doi: 10.1111/1523-1747.ep12466185. [DOI] [PubMed] [Google Scholar]
  5. Dale B. A., Holbrook K. A., Kimball J. R., Hoff M., Sun T. T. Expression of epidermal keratins and filaggrin during human fetal skin development. J Cell Biol. 1985 Oct;101(4):1257–1269. doi: 10.1083/jcb.101.4.1257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Fleckman P., Dale B. A., Holbrook K. A. Profilaggrin, a high-molecular-weight precursor of filaggrin in human epidermis and cultured keratinocytes. J Invest Dermatol. 1985 Dec;85(6):507–512. doi: 10.1111/1523-1747.ep12277306. [DOI] [PubMed] [Google Scholar]
  7. Habets W. J., Hoet M. H., De Jong B. A., Van der Kemp A., Van Venrooij W. J. 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] [Google Scholar]
  8. Habets W. J., de Rooij D. J., Hoet M. H., van de Putte L. B., van Venrooij W. J. 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] [Google Scholar]
  9. Habets W. J., de Rooij D. J., Salden M. H., Verhagen A. P., van Eekelen C. A., van de Putte L. B., van Venrooij W. J. 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] [Google Scholar]
  10. Hoet R. M., Voorsmit R. A., Van Venrooij W. J. 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. doi: 10.1111/j.1365-2249.1991.tb08124.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Janssens X., Veys E. M., Verbruggen G., Declercq L. The diagnostic significance of the antiperinuclear factor for rheumatoid arthritis. J Rheumatol. 1988 Sep;15(9):1346–1350. [PubMed] [Google Scholar]
  12. Kataaha P. K., Mortazavi-Milani S. M., Russell G., Holborow E. J. Anti-intermediate filament antibodies, antikeratin antibody, and antiperinuclear factor in rheumatoid arthritis and infectious mononucleosis. Ann Rheum Dis. 1985 Jul;44(7):446–449. doi: 10.1136/ard.44.7.446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kim H. J., Bernstein I. A. 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. doi: 10.1111/1523-1747.ep12470230. [DOI] [PubMed] [Google Scholar]
  14. Kirstein H., Mathiesen F. K. Antikeratin antibodies in rheumatoid arthritis. Methods and clinical significance. Scand J Rheumatol. 1987;16(5):331–338. doi: 10.3109/03009748709102504. [DOI] [PubMed] [Google Scholar]
  15. Klein F., Bronsveld W., Norde W., Van Romunde L. K., Singer J. M. A modified latex-fixation test for the detection of rheumatoid factors. J Clin Pathol. 1979 Jan;32(1):90–92. doi: 10.1136/jcp.32.1.90. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kurki P., Helve T., Virtanen I. Antibodies to cytoplasmic intermediate filaments in rheumatic diseases. J Rheumatol. 1983 Aug;10(4):558–562. [PubMed] [Google Scholar]
  17. Kurki P., Virtanen I. The detection of human antibodies against cytoskeletal components. J Immunol Methods. 1984 Mar 16;67(2):209–223. doi: 10.1016/0022-1759(84)90462-9. [DOI] [PubMed] [Google Scholar]
  18. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  19. Lazarides E. Intermediate filaments: a chemically heterogeneous, developmentally regulated class of proteins. Annu Rev Biochem. 1982;51:219–250. doi: 10.1146/annurev.bi.51.070182.001251. [DOI] [PubMed] [Google Scholar]
  20. Lerner E. A., Lerner M. R., Janeway C. A., Jr, Steitz J. A. 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. doi: 10.1073/pnas.78.5.2737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mallya R. K., Young B. J., Pepys M. B., Hamblin T. J., Mace B. E., Hamilton E. B. 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] [Google Scholar]
  22. Miossec P., Youinou P., Le Goff P., Moineau M. P. Clinical relevance of antikeratin antibodies in rheumatoid arthritis. Clin Rheumatol. 1982 Sep;1(3):185–189. doi: 10.1007/BF02042772. [DOI] [PubMed] [Google Scholar]
  23. Murozuka T., Fukuyama K., Epstein W. L. Immunochemical comparison of histidine-rich protein in keratohyalin granules and cornified cells. Biochim Biophys Acta. 1979 Aug 28;579(2):334–345. doi: 10.1016/0005-2795(79)90061-8. [DOI] [PubMed] [Google Scholar]
  24. NIENHUIS R. L., MANDEMA E. A NEW SERUM FACTOR IN PATIENTS WITH RHEUMATOID ARTHRITIS; THE ANTIPERINUCLEAR FACTOR. Ann Rheum Dis. 1964 Jul;23:302–305. doi: 10.1136/ard.23.4.302. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Osung O. A., Chandra M., Holborow E. J. Antibody to intermediate filaments of the cytoskeleton. Ann Rheum Dis. 1982 Feb;41(1):69–73. doi: 10.1136/ard.41.1.69. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Osung O. A., Chandra M., Holborow E. J. 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. doi: 10.1136/ard.41.1.74. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ramaekers F. C., Puts J. J., Moesker O., Kant A., Huysmans A., Haag D., Jap P. H., Herman C. J., Vooijs G. P. Antibodies to intermediate filament proteins in the immunohistochemical identification of human tumours: an overview. Histochem J. 1983 Jul;15(7):691–713. doi: 10.1007/BF01002988. [DOI] [PubMed] [Google Scholar]
  28. 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] [Google Scholar]
  29. Ruiter D. J., Mauw B. J., Beyer-Boon M. E. 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] [Google Scholar]
  30. Scherbaum W. A., Youinou P. Y., Le Goff P., Bottazzo G. F. 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] [Google Scholar]
  31. Scott D. L., Delamere J. P., Jones L. J., Walton K. W. Significance of laminar antikeratin antibodies to rat oesophagus in rheumatoid arthritis. Ann Rheum Dis. 1981 Jun;40(3):267–271. doi: 10.1136/ard.40.3.267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Senecal J. L., Rothfield N. F., Oliver J. M. Immunoglobulin M autoantibody to vimentin intermediate filaments. J Clin Invest. 1982 Mar;69(3):716–721. doi: 10.1172/JCI110500. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Sondag-Tschroots I. R., Aaij C., Smit J. W., Feltkamp T. E. The antiperinuclear factor. 1. The diagnostic significance of the antiperinuclear factor for rheumatoid arthritis. Ann Rheum Dis. 1979 Jun;38(3):248–251. doi: 10.1136/ard.38.3.248. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tan E. M. Antinuclear antibodies: diagnostic markers for autoimmune diseases and probes for cell biology. Adv Immunol. 1989;44:93–151. doi: 10.1016/s0065-2776(08)60641-0. [DOI] [PubMed] [Google Scholar]
  35. Toh B. H., Yildiz A., Sotelo J., Osung O., Holborow E. J., Kanakoudi F., Small J. V. Viral infections and IgM autoantibodies to cytoplasmic intermediate filaments. Clin Exp Immunol. 1979 Jul;37(1):76–82. [PMC free article] [PubMed] [Google Scholar]
  36. Vincent C., Serre G., Lapeyre F., Fournié B., Ayrolles C., Fournié A., Soleilhavoup J. P. 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. doi: 10.1136/ard.48.9.712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. WALLER M., TOONE E. C., VAUGHAN E. STUDY OF RHEUMATOID FACTOR IN A NORMAL POPULATION. Arthritis Rheum. 1964 Oct;7:513–520. doi: 10.1002/art.1780070507. [DOI] [PubMed] [Google Scholar]
  38. Westgeest A. A., Boerbooms A. M., Jongmans M., Vandenbroucke J. P., Vierwinden G., van de Putte L. B. Antiperinuclear factor: indicator of more severe disease in seronegative rheumatoid arthritis. J Rheumatol. 1987 Oct;14(5):893–897. [PubMed] [Google Scholar]
  39. Woodcock-Mitchell J., Eichner R., Nelson W. G., Sun T. T. Immunolocalization of keratin polypeptides in human epidermis using monoclonal antibodies. J Cell Biol. 1982 Nov;95(2 Pt 1):580–588. doi: 10.1083/jcb.95.2.580. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. 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. doi: 10.1007/BF00541178. [DOI] [PubMed] [Google Scholar]
  41. Youinou P., Le Goff P., Colaco C. B., 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. doi: 10.1136/ard.44.7.450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Youinou P., Le Goff P., Miossec P., Moineau M. P., 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] [Google Scholar]
  43. Youinou P., Pennec Y., Le Goff P., Ferec C., Morrow W. J., 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] [Google Scholar]
  44. Youinou P., Zabbe C., Eveillaud C., Dewitte J. D., Kerbourc'h J. F., Ferec C., Clavier J. Antiperinuclear activity in lung carcinoma patients. Cancer Immunol Immunother. 1984;18(2):80–81. doi: 10.1007/BF00205738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Young B. J., Mallya R. K., Leslie R. D., Clark C. J., Hamblin T. J. Anti-keratin antibodies in rheumatoid arthritis. Br Med J. 1979 Jul 14;2(6182):97–99. doi: 10.1136/bmj.2.6182.97. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. de Rooij D. J., van de Putte L. B., Habets W. J., Verbeek A. L., van Venrooij W. J. 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. doi: 10.3109/03009748809105271. [DOI] [PubMed] [Google Scholar]
  47. van Muijen G. N., Ruiter D. J., Franke W. W., Achtstätter T., Haasnoot W. H., Ponec M., Warnaar S. O. 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. doi: 10.1016/0014-4827(86)90429-5. [DOI] [PubMed] [Google Scholar]

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