Logo of jclinpathJournal of Clinical PathologyVisit this articleSubmit a manuscriptReceive email alertsContact usBMJ
J Clin Pathol. Mar 2001; 54(3): 187–190.
PMCID: PMC1731369

Antibodies to extractable nuclear antigens. Has technological drift affected clinical interpretation?


Precipitating antibodies to extractable nuclear antigens are important in the diagnosis of connective tissue diseases. Disease associations are defined using gel based techniques. Alternative technologies have been introduced, including passive haemagglutination, enzyme linked immunosorbent assay, and western blotting. This leader contains a review of the literature on the clinical usefulness of these assays, together with knowledge gained from personal experience. Using the example of systemic lupus erythematosus, the sensitivity, specificity, and positive predictive value of the assays for disease is discussed, as is their differences in performance. The conclusion drawn is that disease specificity is method dependent. Validation and audit of performance of the method selected by the investigation laboratory is essential.

Key Words: extractable nuclear antigen • gel precipitation • enzyme linked immunosorbent assay

Full Text

The Full Text of this article is available as a PDF (96K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • HOLMAN HR, DEICHER HR, KUNKEL HG. The L. E. cell and the L. E. serum factors. Bull N Y Acad Med. 1959 Jul;35(7):409–418. [PMC free article] [PubMed]
  • Tan EM, Kunkel HG. Characteristics of a soluble nuclear antigen precipitating with sera of patients with systemic lupus erythematosus. J Immunol. 1966 Mar;96(3):464–471. [PubMed]
  • Tan EM, Fritzler MJ, McDougal JS, McDuffie FC, Nakamura RM, Reichlin M, Reimer CB, Sharp GC, Schur PH, Wilson MR, et al. Reference sera for antinuclear antibodies. I. Antibodies to native DNA, Sm, nuclear RNP, and SS-B/La. Arthritis Rheum. 1982 Aug;25(8):1003–1005. [PubMed]
  • Tan EM, Cohen AS, Fries JF, Masi AT, McShane DJ, Rothfield NF, Schaller JG, Talal N, Winchester RJ. The 1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1982 Nov;25(11):1271–1277. [PubMed]
  • Isenberg DA, Maddison PJ. Detection of antibodies to double stranded DNA and extractable nuclear antigen. J Clin Pathol. 1987 Nov;40(11):1374–1381. [PMC free article] [PubMed]
  • Charles PJ, van Venrooij WJ, Maini RN. The Consensus Workshops for the Detection of Autoantibodies to Intracellular Antigens in Rheumatic Diseases: 1989-1992. Clin Exp Rheumatol. 1992 Sep-Oct;10(5):507–511. [PubMed]
  • Arnett FC, Hamilton RG, Roebber MG, Harley JB, Reichlin M. Increased frequencies of Sm and nRNP autoantibodies in American blacks compared to whites with systemic lupus erythematosus. J Rheumatol. 1988 Dec;15(12):1773–1776. [PubMed]
  • Field M, Williams DG, Charles P, Maini RN. Specificity of anti-Sm antibodies by ELISA for systemic lupus erythematosus: increased sensitivity of detection using purified peptide antigens. Ann Rheum Dis. 1988 Oct;47(10):820–825. [PMC free article] [PubMed]
  • Notman DD, Kurata N, Tan EM. Profiles of antinuclear antibodies in systemic rheumatic diseases. Ann Intern Med. 1975 Oct;83(4):464–469. [PubMed]
  • Siracusano A, Agelli M, Ioppolo S, Quintieri F, Bombardieri S. Detection of anti-extractable nuclear antigens in connective tissue diseases: comparison between passive hemagglutination, counterimmunoelectrophoresis and double immunodiffusion. Ric Clin Lab. 1985 Jan-Mar;15(1):33–38. [PubMed]
  • McCain GA, Bell DA, Chodirker WB, Komar RR. Antibody to extractable nuclear antigen in the rheumatic diseases. J Rheumatol. 1978 Winter;5(4):399–406. [PubMed]
  • Hamburger M, Hodes S, Barland P. The incidence and clinical significance of antibodies to extractable nuclear antigens. Am J Med Sci. 1977 Jan-Feb;273(1):21–28. [PubMed]
  • Venables PJ, Charles PJ, Buchanan RR, Yi T, Mumford PA, Schrieber L, Room GR, Maini RN. Quantitation and detection of isotypes of anti-SS-B antibodies by ELISA and Farr assays using affinity purified antigens. An approach to the investigation of Sjögren's syndrome and systemic lupus erythematosus. Arthritis Rheum. 1983 Feb;26(2):146–155. [PubMed]
  • Yamagata H, Harley JB, Reichlin M. Molecular properties of the Ro/SSA antigen and enzyme-linked immunosorbent assay for quantitation of antibody. J Clin Invest. 1984 Aug;74(2):625–633. [PMC free article] [PubMed]
  • Maddison PJ, Skinner RP, Vlachoyiannopoulos P, Brennand DM, Hough D. Antibodies to nRNP, Sm, Ro(SSA) and La(SSB) detected by ELISA: their specificity and inter-relations in connective tissue disease sera. Clin Exp Immunol. 1985 Nov;62(2):337–345. [PMC free article] [PubMed]
  • Meilof JF, Bantjes I, De Jong J, Van Dam AP, Smeenk RJ. The detection of anti-Ro/SS-A and anti-La/SS-B antibodies. A comparison of counterimmunoelectrophoresis with immunoblot, ELISA, and RNA-precipitation assays. J Immunol Methods. 1990 Oct 19;133(2):215–226. [PubMed]
  • Bizzaro N, Tozzoli R, Tonutti E, Piazza A, Manoni F, Ghirardello A, Bassetti D, Villalta D, Pradella M, Rizzotti P. Variability between methods to determine ANA, anti-dsDNA and anti-ENA autoantibodies: a collaborative study with the biomedical industry. J Immunol Methods. 1998 Oct 1;219(1-2):99–107. [PubMed]
  • Abu-Shakrah M, Krupp M, Argov S, Buskila D, Slor H, Shoenfeld Y. The detection of anti-Sm-RNP activity in sera of patients with monoclonal gammopathies. Clin Exp Immunol. 1989 Mar;75(3):349–353. [PMC free article] [PubMed]
  • Hardiman KL, Horn S, Manoharan A, Phadke K, Gibson J, McGuigan L, Sturgess A. Rheumatic autoantibodies in the sera of patients with paraproteins. Clin Exp Rheumatol. 1994 Jul-Aug;12(4):363–368. [PubMed]
  • van Venrooij WJ, Charles P, Maini RN. The consensus workshops for the detection of autoantibodies to intracellular antigens in rheumatic diseases. J Immunol Methods. 1991 Jul 5;140(2):181–189. [PubMed]
  • Boire G, Lopez-Longo FJ, Lapointe S, Ménard HA. Sera from patients with autoimmune disease recognize conformational determinants on the 60-kd Ro/SS-A protein. Arthritis Rheum. 1991 Jun;34(6):722–730. [PubMed]
  • Itoh Y, Itoh K, Frank MB, Reichlin M. Autoantibodies to the Ro/SSA autoantigen are conformation dependent. II: Antibodies to the denatured form of 52 kD Ro/SSA are a cross reacting subset of antibodies to the native 60 kD Ro/SSA molecule. Autoimmunity. 1992;14(2):89–95. [PubMed]
  • Reichlin M, Rader M, Harley JB. Autoimmune response to the Ro/SSA particle is directed to the human antigen. Clin Exp Immunol. 1989 Jun;76(3):373–377. [PMC free article] [PubMed]
  • Van Duijnhoven HL, Van De Warenburg FJ, Willems RJ, Ermens AM. A comparison of ELISA assays as routine diagnostic test for detection of autoantibodies against extractable nuclear antigens. Clin Biochem. 1999 Apr;32(3):179–183. [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]
  • Ben-Chetrit E, Fox RI, Tan EM. Dissociation of immune responses to the SS-A (Ro) 52-kd and 60-kd polypeptides in systemic lupus erythematosus and Sjögren's syndrome. Arthritis Rheum. 1990 Mar;33(3):349–355. [PubMed]
  • García Lerma JG, Mendoza AZ, Ramos MJ, Sequí J. Evaluation of recombinant Ro/SSA, La/SSB, Sm, and U1 RNP autoantigens in clinical diagnosis. J Clin Lab Anal. 1995;9(1):52–58. [PubMed]
  • Smolen JS, Butcher B, Fritzler MJ, Gordon T, Hardin J, Kalden JR, Lahita R, Maini RN, Reeves W, Reichlin M, et al. Reference sera for antinuclear antibodies. II. Further definition of antibody specificities in international antinuclear antibody reference sera by immunofluorescence and western blotting. Arthritis Rheum. 1997 Mar;40(3):413–418. [PubMed]
  • de Vlam K, De Keyser F, Verbruggen G, Vandenbossche M, Vanneuville B, D'Haese D, Veys EM. Detection and identification of antinuclear autoantibodies in the serum of normal blood donors. Clin Exp Rheumatol. 1993 Jul-Aug;11(4):393–397. [PubMed]
  • Ermens AA, Bayens AJ, van Gemert AC, van Duijnhoven JL. Simple dot-blot method evaluated for detection of antibodies against extractable nuclear antigens. Clin Chem. 1997 Dec;43(12):2420–2422. [PubMed]
  • Sulcebe G, Morcka K. Diagnostic and prognostic significance of different antinuclear antibodies in more than 1000 consecutive Albanian patients with rheumatic diseases. Clin Exp Rheumatol. 1992 May-Jun;10(3):255–261. [PubMed]
  • Sánchez-Guerrero J, Lew RA, Fossel AH, Schur PH. Utility of anti-Sm, anti-RNP, anti-Ro/SS-A, and anti-La/SS-B (extractable nuclear antigens) detected by enzyme-linked immunosorbent assay for the diagnosis of systemic lupus erythematosus. Arthritis Rheum. 1996 Jun;39(6):1055–1061. [PubMed]
  • Zimmermann-Górska I, Potocka-Michajluk U. Comparative evaluation of various methods of detecting antibodies against soluble nuclear antigens. Arch Immunol Ther Exp (Warsz) 1982;30(1-2):89–94. [PubMed]
  • Bresnihan B, Bunn C, Snaith ML, Hughes GR. Antiribonucleoprotein antibodies in connective tissue diseases: estimation by counterimmunoelectrophoresis. Br Med J. 1977 Mar 5;1(6061):610–611. [PMC free article] [PubMed]
  • Struckmann J, Worning P, Manthorpe R, Bendixen G. Detection of antibody against extractable nuclear antigen by an enzyme-linked immuno-sorbent assay. Results from patients with rheumatic and internal medical diseases. Allergy. 1985 Aug;40(6):442–446. [PubMed]
  • White PJ, Hoch SO. Definition of the antigenic polypeptides in the Sm and RNP ribonucleoprotein complexes. Biochem Biophys Res Commun. 1981 Sep 16;102(1):365–371. [PubMed]

Articles from Journal of Clinical Pathology are provided here courtesy of BMJ Group


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...