Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter February 10, 2018

The importance of detecting anti-DFS70 in routine clinical practice: comparison of different care settings

  • Carolien Bonroy EMAIL logo , Sofie Schouwers , Mario Berth , Muriel Stubbe , Yves Piette , Ilse Hoffman , Katrien Devreese and Lieve Van Hoovels

Abstract

Background:

Screening for antinuclear antibodies by indirect immunofluorescence (ANA-IIF) is essential in the diagnostic workup of ANA-associated autoimmune rheumatic diseases (AARDs). However, also healthy individuals may test positive, making the interpretation challenging. Recent reports suggest that dense fine speckled 70 antibodies (anti-DFS70) may facilitate this challenge. Here, we investigate their clinical importance based on data from four Belgian laboratories (one primary, two secondary and one tertiary care).

Methods:

At least one specific DFS70 assay (DFS70 IgG ELISA or lineblot [Euroimmun, full length antigen] and/or DFS70 IgG CLIA [Inova Diagnostics, truncated antigen]) was performed on four consecutive cohorts of homogeneous-like ANA-IIF samples (n=697). Co-occurrence with AARD-specific ANA and clinical information were documented in the anti-DFS70-positive samples.

Results:

Using a combination of solid phase techniques, we found between 7.6% and 26% anti-DFS70 in the different cohorts. Focusing on anti-DFS70 CLIA-positive samples without co-occurrence of AARD-specific ANA, we observed a trend towards lower frequency in tertiary (8% [p=0.0786]) and secondary care (12% [p=0.1275] and 6% [p<0.001]) compared to primary care (21%). Moreover, in this specific subpopulation, AARD was less frequent (0%–50% compared to 6%–77% in the total anti-DFS70-positive group).

Conclusions:

Anti-DFS70 prevalence depends on the applied assay and care setting. Our data suggest that, for an ANA-IIF-positive patient, it is rather the absence of AARD-associated ANA and clinical symptoms that contribute to the exclusion of AARD than the presence of anti-DFS70. Nevertheless, isolated anti-DFS70 helps to clarify positive ANA-IIF results, especially if pretest probability for AARD is low.

Acknowledgments

We thank Euroimmun and Werfen/Inova Diagnostics for the donation of the assays. We are grateful to Julie Jacobs and Jelle Smet (OLVA), Astrid Muyldermans (GZA) and the laboratory technicians of the different participating centers for their most valuable efforts.

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

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. 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.

References

1. Mahler M, Meroni PL, Bossuyt X, Fritzler MJ. Current concepts and future directions for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies. J Immunol Res 2014;2014:315179.10.1155/2014/315179Search in Google Scholar

2. 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;39:2104–10.10.3899/jrheum.120598Search in Google Scholar

3. Agmon-Levin N, Damoiseaux J, Kallenberg C, Sack U, Witte T, Herold M, et al. International recommendations for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies. Ann Rheum Dis 2014;73:17–23.10.1136/annrheumdis-2013-203863Search in Google Scholar

4. Op De Beeck K, Vermeersch P, Verschueren P, Westhovens R, Marien G, Blockmans D, et al. Detection of antinuclear antibodies by indirect immunofluorescence and by solid phase assay. Autoimmun Rev 2011;10:801–8.10.1016/j.autrev.2011.06.005Search in Google Scholar

5. Bonroy C, Smith V, Van Steendam K, Van Praet J, Deforce D, Devreese K, et al. The integration of the detection of systemic sclerosis-associated antibodies in a routine laboratory setting: comparison of different strategies. Clin Chem Lab Med 2013;51:2151–60.10.1515/cclm-2013-0211Search in Google Scholar

6. 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;2013:703759.10.1155/2013/703759Search in Google Scholar

7. Seelig CA, Bauer O, Seelig HP. Autoantibodies against DFS70/LEDGF exclusion markers for systemic autoimmune rheumatic diseases (SARD). Clin Lab 2016;62:499–517.10.7754/Clin.Lab.2015.150905Search in Google Scholar

8. Ochs RL, Mahler M, Basu A, Rios-Colon L, Sanchez TW, Andrade LE, et al. The significance of autoantibodies to DFS70/LEDGFp75 in health and disease: integrating basic science with clinical understanding. Clin Exp Med 2016;16:273–93.10.1007/s10238-015-0367-0Search in Google Scholar

9. Chan EK, Damoiseaux J, de Melo Cruvinel W, Carballo OG, Conrad K, Francescantonio PL, et al. Report on the second International Consensus on ANA Pattern (ICAP) workshop in Dresden 2015. Lupus 2016;25:797–804.10.1177/0961203316640920Search in Google Scholar

10. Ochs RL. Autoantibodies and interstitial cystitis. Clin Lab Med 1997;17:571–9.10.1016/S0022-5347(17)35023-1Search in Google Scholar

11. Yamada K, Senju S, Shinohara T, Nakatsura T, Murata Y, Ishihara M, et al. Humoral immune response directed against LEDGF in patients with VKH. Immunol Lett 2001;78:161–8.10.1016/S0165-2478(01)00243-7Search in Google Scholar

12. Ochs RL, Muro Y, Si Y, Ge H, Chan EK, Tan EM. Autoantibodies to DFS 70 kd/transcription coactivator p75 in atopic dermatitis and other conditions. J Allergy Clin Immunol 2000;105(6 Pt 1):1211–20.10.1067/mai.2000.107039Search in Google Scholar

13. Muro Y, Sugiura K, Morita Y, Tomita Y. High concomitance of disease marker autoantibodies in anti-DFS70/LEDGF autoantibody-positive patients with autoimmune rheumatic disease. Lupus 2008;17:171–6.10.1177/0961203307086311Search in Google Scholar

14. Ayaki M, Ohoguro N, Azuma N, Majima Y, Yata K, Ibaraki N, et al. Detection of cytotoxic anti-LEDGF autoantibodies in atopic dermatitis. Autoimmunity 2002;35:319–27.10.1080/0891693021000003198Search in Google Scholar

15. 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;50:892–900.10.1002/art.20096Search in Google Scholar

16. Ochs RL, Stein TW, Jr., Peebles CL, Gittes RF, Tan EM. Autoantibodies in interstitial cystitis. J Urol 1994;151:587–92.10.1016/S0022-5347(17)35023-1Search in Google Scholar

17. Mariz HA, Sato EI, 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;63:191–200.10.1002/art.30084Search in Google Scholar PubMed

18. Kuwabara N, Itoh Y, Igarshi T, Fukunaga Y. Autoantibodies to lens epithelium-derived growth factor/transcription co-activator P75 (LEDGF/P75) in children with chronic nonspecific complaints and with positive antinuclear antibodies. Autoimmunity 2009;42:492–6.10.1080/08916930902736663Search in Google Scholar PubMed

19. Bizzaro N, Tonutti E, Villalta D. Recognizing the dense fine speckled/lens epithelium-derived growth factor/p75 pattern on HEP-2 cells: not an easy task! Comment on the article by Mariz et al. Arthritis Rheum 2011;63:4036–7; author reply 7–8.10.1002/art.30621Search in Google Scholar PubMed

20. Bizzaro N, Pesente F, Cucchiaro F, Infantino M, Tampoia M, Villalta D, et al. Anti-DFS70 antibodies detected by immunoblot methods: A reliable tool to confirm the dense fine speckles ANA pattern. J Immunol Methods 2016;436:50–3.10.1016/j.jim.2016.06.008Search in Google Scholar PubMed

21. 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 Rheum 2015;42:2419–26.10.3899/jrheum.150567Search in Google Scholar PubMed

22. 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 Rheum 2005;32:2144–9.Search in Google Scholar

23. 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;1107:174–83.10.1196/annals.1381.019Search in Google Scholar PubMed

24. Pazini AM, Fleck J, dos Santos RS, Beck ST. Clinical relevance and frequency of cytoplasmic and nuclear dense fine speckled patterns observed in ANA-HEp-2. Revista Brasileira de Reumatologia 2010;50:655–60.10.1590/S0482-50042010000600006Search in Google Scholar

25. Fitch-Rogalsky C, Steber W, Mahler M, Lupton T, Martin L, Barr SG, et al. Clinical and serological features of patients referred through a rheumatology triage system because of positive antinuclear antibodies. PloS one 2014;9:e93812.10.1371/journal.pone.0093812Search in Google Scholar PubMed PubMed Central

26. 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 2017. PMID: 28770702 [Epub ahead of print].Search in Google Scholar

27. Bentow C, Fritzler MJ, Mummert E, Mahler M. Recognition of the dense fine speckled (DFS) pattern remains challenging: results from an international internet-based survey. Auto Immun Highlights 2016;7:8.10.1007/s13317-016-0081-2Search in Google Scholar PubMed PubMed Central

28. Basu A, Woods-Burnham L, Ortiz G, Rios-Colon L, Figueroa J, Albesa R, et al. Specificity of antinuclear autoantibodies recognizing the dense fine speckled nuclear pattern: preferential targeting of DFS70/LEDGFp75 over its interacting partner MeCP2. Clin Immunol 2015;161:241–50.10.1016/j.clim.2015.07.014Search in Google Scholar PubMed PubMed Central

29. Gundin S, Irure-Ventura J, Asensio E, Ramos D, Mahler M, Martinez-Taboada V, et al. Measurement of anti-DFS70 antibodies in patients with ANA-associated autoimmune rheumatic diseases suspicion is cost-effective. Auto Immun Highlights 2016;7:10.10.1007/s13317-016-0082-1Search in Google Scholar PubMed PubMed Central

Received: 2017-6-21
Accepted: 2018-1-3
Published Online: 2018-2-10
Published in Print: 2018-6-27

©2018 Walter de Gruyter GmbH, Berlin/Boston

Downloaded on 26.4.2024 from https://www.degruyter.com/document/doi/10.1515/cclm-2017-0541/html
Scroll to top button