CLINICAL SIGNIFICANCE OF ANTIPERINUCLEAR FACTOR AND ANTIKERATIN ANTIBODY FOR RHEUMATOID ARTHRITIS

Abstract

Rheumatoid Factor (RF) is the only serologic marker used in the diagnosis of rheumatoid arthritis (RA). Since it is present in a number of diseases other than RA and found negative in some patients with RA, diagnostic utility of RF has some limitations. Several more specific autoantibodies detected in the sera of RA patients are not routinely tested. Antiperinuclear factor (APF) and antikeratin antibodies (AKA) are two of these antibodies. In previously reported series, the APF was present in 49% and 87% of RA patients with a specificity between 73% and 99%. AKA was detected positive in 36% to 59% of the RA patients, and its specificity was 88% to 99. In this article, we have reviewed characteristics, significance in the pathogenesis and the diagnostic use of these two antibodies in RA.
Key Words: Rheumatoid Arthritis,
Autoantibodies, Antiperinuclear Factor, Antikeratin antibody.

References

1. Firestein OS. Etiology and pathogenesis of rheumatoid arthritis. In: Kelley WM, Ruddy S, Marris ED, Sledge CB, Eds. Textbook of Rheumatology. Fhiledelphia: WB Saunders, 1997:851-897.
2. Shmerling RM, Delbanco TL. The rheumatoid factor: an analysis of clinical utility. The Am J Med 1991;91:528-534.
3. Blackburn WD, Chatham WW. Laboratory findings in rheumatoid arthritis. In: Koopman W, Ed. Arthritis and Allied Conditions. A Textbook of Rheumatology. Maryland: Williams and Wilkins, 1997:1089-1107.
4. Mienhuis RLF, Mandema E, Smids C. A new serum factor in patients with rheumatoid arthritis, the antiperinuclear factor. Ann Rheum Dis 1964;23:302-305.
5. Vivino FB, Mau! QQ. Mistologic and electron microscopic characterization of the antiperinuclear factor antigen. Arthritis Rheum 1990;33:960-969.
6. Youinou F, le Qoft F. The reliability of the antiperinuclear factor test despite the inconstancy of the targeted antigen. J Rheumatol 1994;21:11.
7. Balogh K. Mouth, nose, and paranasal sinuses. In: Stenberg 55, Ed. Histology for pathologists. Fhiledelphia: Lippincott-Raven Publishers, 1997:367-389.
8. Smit JW, Sondag-Tschroots IRM, Aaij C, Feltkamp TEW, Feltkamp-Vroom TM. The antiperinuclear factor. A II. light microscopical and immunofluorescence study on the antigenic substrate. Ann Rheum Dis 1980;39:381-386.

9. Young BJJ, Mallya RK, Leslie RDG, Clark CJM, Mamblin TJ. Antikeratin antibodies in rheumatoid arthritis. BMJ 1979;2:97-99.
10. Aho K, Falusuo T, Kurki P. Marker antibodies
11. of rheumatoid arthritis: Diagnostic and
12. pathogenetic implications. Seminars in Arthritis and Rheumatism 1994;23:379-387.
13. Schellekens GA, de Jong BA W, van den Moogen FMJ, van de Futte LBA, van Venrooij WJ. Citrulline is an essential constituent of antigenic determinants recognized by rheumatoid arthritis-specific antibodies. J Clin Invest 1998,101:273-281.
14. Moet RMA, Boerbooms AMT, Arends M, Ruiter DJ, van Venrooij WJ. Antiperinuclear factor, a marker antibody for rheumatoid arthritis: colocalisation of the perinuclear factor and profilaggrin. Ann Rheum Dis 1991;50:611- 618.
15. ¡3. Kubilus J, Scott I, Marding CR, Yendle J, Kvedar J, Baden MP. The occurrence of profilaggrin and its processing in cultured kératinocytes. J Invest Dermatol 1985;85:513-517.
16. Fleckman P, Dale BA, Mol brook RA. Profilaggrin, a high molecular-weight precursor of filaggrin in human epidermis and cultured kératinocytes. J Invest Dermatol 1985;85:507-512.
17. Sebbag M, Simon M, Vincent C, et al. The perinuclear factor and the so-called antikeratin antibodies are the same rheumatoid arthritis-specific autoantibodies. J Clin Invest 1995;95:2672-2679.
18. Berthelot JM, Maugars Y, Prost A, Youinou P. Rheumatoid arthritis and filaggrin. Rev Rhum Engl Ed 1995;62:127-138.
19. Simon M, Girbal E, Sebbag M, et al. The cytokeratin filament-aggregating protein filaggrin is the target of the so-called ‘antikeratin antibodies" autoantibodies speciFic for rheumatoid arthritis. J Clin Invest 1993,92:1387-1393.
20. Vincent C, de Keyser F, Masson-Bessiere M, Sebbag M, Veys EM, Seera G. Anti-perinuclear factor compared with the so called 'antikeratin' antibodies and antibodies to human epidermis filaggrin, in the diagnosis of arthritis. Ann Rheum Dis 1999;58:42-48.
21. Mackenzie 1C, Miles AEW. The effect of chronical frictional stimulation of hamster cheek pouch epithelium. Arch Oral Biol 1973,18:1341-1349.
22. Youinou P, Le Goff P, Dumay A, Lelong A,
23. Fauquert P, Jouguan J. The antiperinuclear factor: I. Clinical and serological
24. associations. Clin Exp Rheumatol 1990;8:259-264.
25. Arnett FC, Edworthy SM, Bloch DA, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315-324.
26. Schrohenloher RE, Bridges SL Jr. Koopman
27. WJ. Rheumatoid factor. In: Koopman W, Ed. Arthritis and Allied Conditions. A Textbook of Rheumatology. Maryland: Williams and
28. Wilkins, 1997:1109-1130.
29. Berthelot JM, Gamier P, Glemarec J, Flipo RM. Diagnostic value for rheumatoid arthritis of antiperinuclear factor at the 1:100 threshold: study of 600 patients and metaanalysis of the literature. Rev Rheum Engl Ed 1998;65:9-14.
30. Feltkamp TEW, Berthelot JM, Boerbooms AMT, et al. Interlaboratory variability of the
31. Antiperinuclear factor and antikeratin antibody for rheumatoid arthritis
32. perinuclear factor test for rheumatoid artritis. Clin Exp Rheumatol 1993;! 1:57-59.
33. Berthelot JM, Castagne A, Maugars Y, Audrain M, Barrier J, Prost A. High diagnostic value of antiperinuclear factor-IgG. Prospective analysis of 1004 sera diluted 1:100 of more. BrJ Rheumatol 1995;34:87-88.
34. Janssens X, Veys EM, Verbruggen G, Declercq
35. L. The diagnostic significance of the antiperinuclear factor for rheumatoid arthritis. J Rheumatol 1988;5:1346-1350.
36. Kerstens PJSM, Boerbooms AMT, Jeurissen MEC, et al. Antiperinuclear factor and disease activity in rheumatoid arthritis. Longitudinal evaluation during methotraxate and azothioprine therapy. J Rheumatol 1994;21:2190-2194.
37. Westgeest AAA, Boerbooms AMT, Jongmans
38. M, Vandenbroucke J, Vierwinden G, van dePutte LBA. Antiperinuclear factor: indicator of more severe disease in seronegative rheumatoid arthritis. J Rheumatol 1987;14:891-897.
39. Berthelot JM, Maugars Y, Castagne A, Audrain M, Prost A. Antiperinuclear factors are present in polyarthritis before ACR criteria for rheumatoid arthritis are fulfilled. Ann Rheum Dis 1997;56:123-125.
40. Vincent C, Serre G, Lapeyre E, et al. High diagnostic value in rheumatoid arthritis of antibodies to the stratum corneum of rat esophagus epithelium, so-called anti-keratin antibodies". Ann Rheum Dis 1989;48:712- 722.
41. Slack SL, Mannik M, Dale BA. Diagnostic value of antibodies to filaggrin in rheumatoid arthritis. J Rheumatol 1998;25:847-850.
42. Alnigenis MHY, Warikoo S, Barland P. Antiperinuclear factor (APE) and antikeratin antibody (AKA): Their diagnostic use in a clinical laboratory setting. J Rheumatol 2000; In press.
43. Schellekens GA, Visser H, DeJong BA W, et al. The dignostic properties of rheumatoid arthritis antibodies recognizing a cyclic citrullinated peptide. Arthritis Rheum 2000;43:155-163.