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Journal of Laboratory Medicine

Official Journal of the German Society of Clinical Chemistry and Laboratory Medicine

Editor-in-Chief: Schuff-Werner, Peter

Ed. by Ahmad-Nejad, Parviz / Bidlingmaier, Martin / Bietenbeck, Andreas / Conrad, Karsten / Findeisen, Peter / Fraunberger, Peter / Ghebremedhin, Beniam / Holdenrieder, Stefan / Kiehntopf, Michael / Klein, Hanns-Georg / Kohse, Klaus P. / Kratzsch, Jürgen / Luppa, Peter B. / Meyer, Alexander von / Nebe, Carl Thomas / Orth, Matthias / Röhrig-Herzog, Gabriele / Sack, Ulrich / Steimer, Werner / Weber, Thomas / Wieland, Eberhard / Winter, Christof / Zettl, Uwe K.


IMPACT FACTOR 2018: 0.389

CiteScore 2018: 0.22

SCImago Journal Rank (SJR) 2018: 0.156
Source Normalized Impact per Paper (SNIP) 2018: 0.089

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2567-9449
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Volume 43, Issue 3

Issues

Clinical significance of anti-DFS70 antibody in antinuclear antibody-positive samples with a dense fine speckled pattern

Sun Hoe Koo
  • Department of Laboratory Medicine, College of Medicine, Chungnam National University Hospital, Daejeon, South Korea
  • Other articles by this author:
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/ Jimyung Kim
  • Corresponding author
  • Department of Laboratory Medicine, College of Medicine, Chungnam National University Hospital, Daejeon, South Korea
  • Email
  • Other articles by this author:
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/ Seon Young Kim
  • Department of Laboratory Medicine, College of Medicine, Chungnam National University Hospital, Daejeon, South Korea
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/ Gye Cheol Kwon
  • Department of Laboratory Medicine, College of Medicine, Chungnam National University Hospital, Daejeon, South Korea
  • Other articles by this author:
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Published Online: 2019-05-22 | DOI: https://doi.org/10.1515/labmed-2019-0036

Abstract

Background

When the dense fine speckled (DFS) pattern-antinuclear antibodies (ANA) are detected in the indirect immunofluorescence (IIF) assay, the presence of anti-dense fine speckles 70 (DFS70) antibodies has been suggested to facilitate the exclusion of ANA-associated rheumatic diseases (AARD). We evaluated the potential use of anti-DFS70 antibodies for verifying AARD in patients with a positive ANA result of the DFS pattern.

Methods

A total of 5509 patients who were requested ANA testing were included. The DFS pattern was confirmed using two IIF assays. Semiquantitative DFS70 ELISA (Euroimmun, Germany) was examined in samples with the DFS pattern.

Results

Among 639 ANA-positive patients, 19.6% displayed the DFS pattern. And 17.6% of patients with the DFS pattern were diagnosed with AARD. The low titer of 1:80 was more prevalent in the non-AARD group than in the AARD group (64.1% vs. 4.5%, p < 0.0001). Anti-DFS70 antibodies were positive in 60.0% of patients with the DFS pattern. The frequency of anti-DFS70 positivity was higher in the non-rheumatic disease (NRD) group (74.2%) than in the other rheumatic disease group (43.2%, p = 0.003) and the AARD group (45.5%, p = 0.019).

Conclusions

The DFS pattern is present in both AARD and non-AARD cases. In the DFS pattern, a low titer of 1:80 and isolated anti-DFS70 antibodies without AARD-associated antibodies represent a low likelihood of AARD. The presence of anti-DFS70 antibodies cannot exclude AARD and should be analyzed in combination with AARD-associated antibodies in the diagnostic algorithm.

Reviewed publication

SackU. ConradK.Edited by:

Keywords: ANA-associated rheumatic diseases; antinuclear antibody; DFS70; indirect immunofluorescence

References

  • 1.

    Meroni PL and Schur PH. ANA screening: an old test with new recommendations. Ann Rheum Dis 2010;69:1420–2.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 2.

    Mariz HA, Sato EL, Barbosa SH, Rodrigues SH, Dellavance A, Andrade LE. Pattern on the antinuclear antibody-HEp-2 test is a critical parameter for discriminating antinuclear antibody-positive healthy individuals and patients with autoimmune rheumatic diseases. Arthritis Rheum 2011;63:191–200.Web of ScienceCrossrefPubMedGoogle Scholar

  • 3.

    Ganapathy V, Casiano CA. Autoimmunity to the nuclear autoantigen DFS70 (LEDGF): what exactly are the autoantibodies trying to tell us? Arthritis Rheum 2004;50:684–8.CrossrefPubMedGoogle Scholar

  • 4.

    Mahler M, Parker T, Peebles CL, Andrade LE, Swart A, Carbone Y, et al. Anti-DFS70/LEDGF antibodies are more prevalent in healthy individuals compared to patients with systemic autoimmune rheumatic diseases. J Rheumatol 2012;39:2104–10.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 5.

    Kang SY, Lee WI. Clinical significance of dense fine speckled pattern in anti-nuclear antibody test using indirect immunofluorescence method. Korean J Lab Med 2009;29:145–51.CrossrefWeb of SciencePubMedGoogle Scholar

  • 6.

    Ge H, Si Y, Roeder RG. Isolation of cDNAs encoding novel transcription coactivators p52 and p75 reveals an alternate regulatory mechanism of transcriptional activation. EMBO J 1998;17:6723–9.CrossrefPubMedGoogle Scholar

  • 7.

    Singh DP, Ohguro N, Kikuchi T, Sueno T, Reddy VN, Yuge K, et al. Lens epithelium-derived growth factor: effects on growth and survival of lens epithelial cells, keratinocytes, and fibroblasts. Biochem Biophys Res Commun 2000;267:373–81.CrossrefPubMedGoogle Scholar

  • 8.

    Infantino M, Shovman O, Pérez D, Grossi V, Manfredi M, Benucci M, et al. A better definition of the anti-DFS70 antibody screening by IIF methods. J Immunol Methods 2018;461:110–6.CrossrefWeb of SciencePubMedGoogle Scholar

  • 9.

    Infantino M, Shovman O, Gilburd B, Manfredi M, Grossi V, Benucci M, et al. Improved accuracy in DFS pattern interpretation using a novel HEp-2 ELITE system. Clin Rheumatol 7 Jan 2019. https://doi.org/10.1007/s10067-018-04412-1 [Epub ahead of print].Web of Science

  • 10.

    Lee H, Kim Y, Han K, Oh EJ. Application of anti-DFS70 antibody and specific autoantibody test algorithms to patients with the dense fine speckled pattern on HEp-2 cells. Scand J Rheumatol 2016;45:122–8.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 11.

    Miyara M, Albesa R, Charuel JL, El Amri M, Fritzler MJ, Ghillani-Dalbin P, et al. Clinical phenotypes of patients with anti-DFS70/LEDGF antibodies in a routine ANA referral cohort. Clin Dev Immunol 2013;2013:703459.Web of ScienceGoogle Scholar

  • 12.

    Conrad K, Röber N, Andrade LE, Mahler M. The clinical relevance of anti-DFS70 autoantibodies. Clin Rev Allergy Immunol 2017;52:202–16.CrossrefPubMedWeb of ScienceGoogle Scholar

  • 13.

    Mahler M, Fritzler MJ. The clinical significance of the dense fine speckled immunofluorescence pattern on HEp-2 Cells for the diagnosis of systemic autoimmune diseases. Clin Dev Immunol 2012;2012:494356.Web of ScienceGoogle Scholar

  • 14.

    Shovman O, Gilburd B, Chayat C, Amital H, Langevitz P, Watad A, et al. Prevalence of anti-DFS70 antibodies in patients with and without systemic autoimmune rheumatic diseases. Clin Exp Rheumatol 2018;36:121–6.PubMedGoogle Scholar

  • 15.

    Chan EK, Damoiseaux J, Carballo OG, Conrad K, de Melo Cruvinel W, Francescantonio PLC, et al. Report of the first international consensus on standardized nomenclature of antinuclear antibody HEp-2 cell patterns 2014–2015. Front Immunol 2015;6:412.PubMedWeb of ScienceGoogle Scholar

  • 16.

    Bizzaro N, Tonutti E, Visentini D, Alessio MG, Platzgummer S, Morozzi G, et al. Antibodies to the lens and cornea in anti-DFS70-positive subjects. Ann N Y Acad Sci 2007;1107:174–83.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 17.

    Mutlu E, Eyigör M, Mutlu D, Gültekin M. Confirmation of anti-DFS70 antibodies is needed in routine clinical samples with DFS staining pattern. Cent Eur J Immunol 2016;41:6–11.Web of SciencePubMedGoogle Scholar

  • 18.

    Dellavance A, Viana VS, Leon EP, Bonfa ES, Andrade LE, Leser PG. The clinical spectrum of antinuclear antibodies associated with the nuclear dense fine speckled immunofluorescence pattern. J Rheumatol 2005;32:2144–9.PubMedGoogle Scholar

  • 19.

    Abeles AM, Abeles M. The clinical utility of a positive antinuclear antibody test result. Am J Med 2013;126:342–8.PubMedWeb of ScienceCrossrefGoogle Scholar

  • 20.

    Watanabe A, Kodera M, Sugiura K, Usuda T, Tan EM, Takasaki Y, et al. Anti-DFS70 antibodies in 597 healthy hospital workers. Arthritis Rheum 2004;50:892–900.CrossrefPubMedGoogle Scholar

  • 21.

    Infantino M, Shovman O, Pérez D, Manfredi M, Grossi V, Benucci M, et al. Anti-DFS70 autoantibodies in undifferentiated connective tissue diseases subjects: what’s on the horizon? Rheumatology 2018; Published online: 03 April 2018. https://doi.org/10.1093/rheumatology/key012.Web of SciencePubMed

  • 22.

    Schmeling H, Mahler M, Levy DM, Moore K, Stevens AM, Wick J, et al. Autoantibodies to dense fine speckles in pediatric diseases and controls. J Rheumatol 2015;42:2419–26.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 23.

    Muro Y, Iwata N, Tanaka Y, Kodera M, Kono M, Akiyama M. Anti-dense fine speckled 70 autoantibodies in Japanese children with dermatomyositis, localized scleroderma, and idiopathic arthritis with iridocyclitis. J Rheumatol 2017;44:711–2.PubMedCrossrefWeb of ScienceGoogle Scholar

  • 24.

    Choi MY, Clarke AE, St Pierre Y, Hanly JG, Urowitz MB, Romero-Diaz J, et al. The prevalence and determinants of anti-DFS70 autoantibodies in an international inception cohort of systemic lupus erythematosus patients. Lupus 2017;26:1051–9.CrossrefWeb of ScienceGoogle Scholar

  • 25.

    Carter JB, Carter S, Saschenbrecker S, Goeckeritz BE. Recognition and relevance of anti-DFS70 autoantibodies in routine antinuclear autoantibodies testing at a community hospital. Front Med (Lausanne) 2018;5:88.Web of ScienceGoogle Scholar

About the article

Correspondence: Jimyung Kim, MD, Department of Laboratory Medicine, College of Medicine, Chungnam National University Hospital, 282 Moonhwa-ro, Jung-gu, Daejeon 35015South Korea, Phone: +82-42-280-7998, Fax: +82-42-257-5365


Received: 2019-03-05

Accepted: 2019-05-04

Published Online: 2019-05-22

Published in Print: 2019-06-26


Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.


Citation Information: Journal of Laboratory Medicine, Volume 43, Issue 3, Pages 149–155, ISSN (Online) 2567-9449, ISSN (Print) 2567-9430, DOI: https://doi.org/10.1515/labmed-2019-0036.

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