The prevalence and determinants of anti-DFS70 autoantibodies in an international inception cohort of systemic lupus erythematosus patients

Abstract

Autoantibodies to dense fine speckles 70 (DFS70) are purported to rule out the diagnosis of SLE when they occur in the absence of other SLE-related autoantibodies. This study is the first to report the prevalence of anti-DFS70 in an early, multinational inception SLE cohort and examine demographic, clinical, and autoantibody associations. Patients were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. The association between anti-DFS70 and multiple parameters in 1137 patients was assessed using univariate and multivariate logistic regression. The frequency of anti-DFS70 was 7.1% (95% CI: 5.7–8.8%), while only 1.1% (95% CI: 0.6–1.9%) were monospecific for anti-DFS70. In multivariate analysis, patients with musculoskeletal activity (Odds Ratio (OR) 1.24 [95% CI: 1.10, 1.41]) or with anti-β2 glycoprotein 1 (OR 2.17 [95% CI: 1.22, 3.87]) were more likely and patients with anti-dsDNA (OR 0.53 [95% CI: 0.31, 0.92]) or anti-SSB/La (OR 0.25 [95% CI: 0.08, 0.81]) were less likely to have anti-DFS70. In this study, the prevalence of anti-DFS70 was higher than the range previously published for adult SLE (7.1 versus 0–2.8%) and was associated with musculoskeletal activity and anti-β2 glycoprotein 1 autoantibodies. However, ‘monospecific’ anti-DFS70 autoantibodies were rare (1.1%) and therefore may be helpful to discriminate between ANA-positive healthy individuals and SLE.

Keywords

Antinuclear antibodies autoantibodies DFS70 SLE

Get full access to this article

View all access options for this article.

References

Mahler

Fritzler

. Epitope specificity and significance in systemic autoimmune diseases. Ann N Y Acad Sci 2010; 1183: 267–287.

Agmon-Levin

Damoiseaux

Kallenberg

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.

Meroni

Schur

. ANA screening: An old test with new recommendations. Ann Rheum Dis 2010; 69: 1420–1422.

Mahler

Parker

Peebles

et al.

Anti-DFS70/LEDGF antibodies are more prevalent in healthy individuals compared to patients with systemic autoimmune rheumatic diseases. J Rheumatol 2012; 39: 2104–2110.

Fitch-Rogalsky

Steber

Mahler

et al.

Clinical and serological features of patients referred through a rheumatology triage system because of positive antinuclear antibodies. PLoS ONE 2014; 9: e93812–e93812.

Bizzaro

Tonutti

Tampoia

et al.

Specific chemoluminescence and immunoadsorption tests for anti-DFS70 antibodies avoid false positive results by indirect immunofluorescence. Clin Chim Acta 2015; 451(Pt B): 271–277.

Nilsson

Voss

Lillevang

. DFS70 autoantibodies are rare in healthy Danish individuals but may still serve as a diagnostic aid. Scand J Immunol 2015; 82: 547–548.

Gundin S, Irure-Ventura V, Asensio E, et al. Measurement of anti-DFS70 antibodies in patients with ANA-associated autoimmune rheumatic diseases suspicion is cost-effective. AutoImmun Highlights 2016; 7: 10-0082.

Conrad K, Rober N, Andrade LE, et al. The clinical relevance of anti-DFS70 autoantibodies. Clin Rev Allergy Immunol 2016; EPub ahead of print. PMID: 27350273.

10.

Muro

Sugiura

Morita

et al.

High concomitance of disease marker autoantibodies in anti-DFS70/LEDGF autoantibody-positive patients with autoimmune rheumatic disease. Lupus 2008; 17: 171–176.

11.

Schmeling

Mahler

Levy

et al.

Autoantibodies to dense fine speckles in pediatric diseases and controls. J Rheumatol 2015; 42: 2419–2426.

12.

Miyara

Albesa

Charuel

et al.

Clinical phenotypes of patients with anti-DFS70/LEDGF antibodies in a routine ANA referral cohort. Clin Dev Immunol 2013; 2013: 703759–703759.

13.

Mahler

Fritzler

. 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: 494356–494356.

14.

Fritzler

. Choosing wisely: Review and commentary on anti-nuclear antibody (ANA) testing. Autoimmun Rev 2016; 15: 272–280.

15.

Arbuckle

McClain

Rubertone

et al.

Development of autoantibodies before the clinical onset of systemic lupus erythematosus. N Engl J Med 2003; 349: 1526–1533.

16.

Eriksson

Kokkonen

Johansson

et al.

Autoantibodies predate the onset of systemic lupus erythematosus in northern Sweden. Arthritis Res Ther 2011; 13: R30–R30.

17.

Isenberg

Ramsey-Goldman

Gladman

et al.

The Systemic Lupus International Collaborating Clinics (SLICC) group – it was 20 years ago today. Lupus 2011; 20: 1426–1432.

18.

Urowitz

Gladman

Ibanez

et al.

American College of Rheumatology criteria at inception, and accrual over 5 years in the SLICC inception cohort. J Rheumatol 2014; 41: 875–880.

19.

Hochberg

. Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 1997; 40: 1725–1725.

20.

Bombardier

Gladman

Urowitz

et al.

Derivation of the SLEDAI. A disease activity index for lupus patients. The Committee on Prognosis Studies in SLE. Arthritis Rheum 1992; 35: 630–640.

21.

Pisetsky D, Thompson D, Wajdula J, et al. Negative results of antinuclear antibody (ANA) testing in clncial trials of systemic lupus erythematosus (SLE) may be due to assay variability. Arthritis Rheumatol 2016; 68(Suppl 10), Abstract #1047.

22.

Fritzler

Hanson

Miller

et al.

Specificity of autoantibodies to SS-A/Ro on a transfected and overexpressed human 60 kDa Ro autoantigen substrate. J Clin Lab Anal 2002; 16: 103–108.

23.

Bentow

Rosenblum

Correia

et al.

Development and multi-center evaluation of a novel immunoadsorption method for anti-DFS70 antibodies. Lupus 2016; 25: 897–904.

24.

Orbai

Truedsson

Sturfelt

et al.

Anti-C1q antibodies in systemic lupus erythematosus. Lupus 2015; 24: 42–49.

25.

Ochs RL, Muro Y, Si YZ, et al. Autoantibodies to DFS70 kd/transcription coactivator p75 in atopic dermatitis and other conditions. J Allergy Clin Immunol 2000; 105: 1211–1220.

26.

Ochs RL, Mahler M, Basu A, et al. The significance of autoantibodies to DFS70/LEDGFp75 in health and disease: Integrating basic science with clinical understanding. Clin Exp Med 2016; 16: 273–293.

27.

Daniels

Zhang

Gutierrez

et al.

Antinuclear autoantibodies in prostate cancer: Immunity to LEDGF/p75, a survival protein highly expressed in prostate tumors and cleaved during apoptosis. Prostate 2005; 62: 14–26.

28.

Maertens

Cherepanov

Pluymers

et al.

LEDGF/p75 is essential for nuclear and chromosomal targeting of HIV-1 integrase in human cells. J Biol Chem 2003; 278: 33528–33539.

29.

Basu

Sanchez

Casiano

. DFS70/LEDGFp75: An enigmatic autoantigen at the interface between autoimmunity, AIDS, and cancer. Front Immunol 2015; 6: 116–116.

30.

Basu A, Rojas H, Banerjee H et al. Expression of the stress response oncoprotein LEDGF/p75 in human cancer: a study of 21 tumor types. PLoS.ONE 2012; 7: e30132.

31.

Roeder

. Isolation of cDNAs encoding novel transcription coactivators p52 and p75 reveals an alternate regulatory mechanism of transcriptional activation. EMBO J 1998; 17: 6723–6729.

32.

Hoftberger

Dalmau

Graus

. Clinical neuropathology practice guide 5-2012: Updated guideline for the diagnosis of antineuronal antibodies. Clin Neuropathol 2012; 31: 337–341.

33.

Watanabe

Kodera

Sugiura

et al.

Anti-DFS70 antibodies in 597 healthy hospital workers. Arthritis Rheum 2004; 50: 892–900.

34.

Mariz

Sato

Barbosa

et al.

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.

35.

Shoenfeld

Szyper-Kravitz

Witte

et al.

Autoantibodies against protective molecules – C1q, C-reactive protein, serum amyloid P, mannose-binding lectin, and apolipoprotein A1: Prevalence in systemic lupus erythematosus. Ann N Y Acad Sci 2007; 1108: 227–239.

36.

Muro

Sugiura

Nakashima

et al.

Low prevalence of anti-DFS70/LEDGF antibodies in patients with dermatomyositis and other systemic autoimmune rheumatic diseases. J Rheumatol 2013; 40: 92–93.

37.

Mahler

Meroni

Andrade

et al.

Towards a better understanding of the clinical association of anti-DFS70 autoantibodies. Autoimmun Rev 2016; 15: 198–201.

38.

Marlet

Ankri

Charuel

et al.

Thrombophilia associated with anti-DFS70 autoantibodies. PLoS ONE 2015; 10: e0138671–e0138671.

39.

Bentow

Fritzler

Mummert

et al.

Recognition of the dense fine speckled (DFS) pattern remains challenging: Results from an international internet-based survey. Auto Immun Highlights 2016; 7: 8–8.

40.

Bizzaro N, Pesente F, Cucchiaro F, et al. Anti-DFS70 antibodies detected by immunoblot methods: A reliable tool to confirm the dense fine speckles ANA pattern. J Immunol Methods 2016; 46: 50–53.

41.

Lee

Kim

Han

et al.

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: 122–128.

42.

Basu

Woods-Burnham

Ortiz

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; 16: 241–250.

Supplementary Material

Please find the following supplemental material available below.

For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.

For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.

0.00 MB

0.14 MB