The Prevalence of Anti-DFS70 Antibodies in an International Inception Cohort of Systemic Lupus Erythematosus

May Choi¹, John G. Hanly², Murray Urowitz^3,4, Juanita Romero-Diaz⁵, Caroline Gordon⁶, Sang-Cheol Bae⁷, Sasha Bernatsky⁸, Daniel J Wallace⁹, Joan T. Merrill¹⁰, David A. Isenberg¹¹, Anisur Rahman¹², Ellen M. Ginzler¹³, Paul R. Fortin¹⁴, Dafna Gladman¹⁵, Jorge Sanchez-Guerrero¹⁶, Michelle Petri¹⁷, Ian N. Bruce¹⁸, Mary Anne Dooley¹⁹, Rosalind Ramsey-Goldman²⁰, Cynthia Aranow²¹, Graciela S. Alarcon²², Kristján Steinsson²³, Ola Nived²⁴, Gunnar K. Sturfelt²⁵, Susan Manzi²⁶, Munther Khamashta²⁷, Ronald F. van Vollenhoven²⁸, Asad Zoma²⁹, Guillermo Ruiz-Irastorza³⁰, S. Sam Lim³¹, Thomas Stoll³², Murat Inanc³³, Kenneth C. Kalunian³⁴, Diane L. Kamen³⁵, Peter Maddison³⁶, Christine A. Peschken³⁷, Søren Jacobsen³⁸, Anca Askanase³⁹, Jill P. Buyon⁴⁰, W. Winn Chatham⁴¹, Manuel Ramos-Casals⁴², Yvan St. Pierre⁴³, Ann E. Clarke⁴⁴ and Marvin J. Fritzler¹, ¹Medicine, University of Calgary, Calgary, AB, Canada, ²Rheumatology, Division of Rheumatology, Capital Health and Dalhousie University, Halifax, NS, Canada, ³Rheumatology, TWH, Toronto, ON, Canada, ⁴Rheumatology, U of Toronto, Toronto Western Hospital, Toronto, ON, Canada, ⁵Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico city, Mexico, ⁶Rheumatology (East Wing), Medical School, Birmingham, United Kingdom, ⁷Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, South Korea, ⁸Rheum/Clin. Epid., McGill MUHC/RVH, Montreal, QC, Canada, ⁹Cedars-Sinai Medical Center, West Hollywood, CA, ¹⁰Clinical Pharmacology, Oklahoma Medical Research Foundation, Oklahoma City, OK, ¹¹Rayne Institute, Centre for Rheumatology Research, UCL Division of Medicine, London, United Kingdom, ¹²Centre for Rheumatology Research, U College of London, London, United Kingdom, ¹³Medicine/Box 42, SUNY-Downstate, Brooklyn, NY, ¹⁴Rheumatology, University of Laval, Quebec, QC, Canada, ¹⁵Rheumatology, University of Toronto, Toronto Western Hospital, Toronto, ON, Canada, ¹⁶Rheumatology, Toronto Western Hospital, Toronto, ON, Canada, ¹⁷Rheumatology, Johns Hopkins University Hospital, Baltimore, MD, ¹⁸Central Manchester University Hospital NHS Foundation Trust and Manchester Academic Health Science Centre, NIHR Manchester Musculoskeletal Biomedical Research Unit, Manchester, United Kingdom, ¹⁹UNC Kidney Centre, Chapel Hill, NC, ²⁰Northwestern University Feinberg School of Medicine, Chicago, IL, ²¹Feinstein Institute for Medical Research, Mahasset, NY, ²²Medicine, University of Alabama at Birmingham, Birmingham, AL, ²³Rheumatology, Univ. Hospital, Reykjavik, Iceland, ²⁴Rheumatology, Inst of Clinical sciences, Lund, Sweden, ²⁵Department of Rheumatology, Univ Hospital Lund, Lund, Sweden, ²⁶Rheumatology, Allegheny Health Network, Pittsburgh, PA, ²⁷Graham Hughes Lupus Research Laboratory, The Rayne Institute, St Thomas' Hospital, London, United Kingdom, ²⁸Department of Medicine, Rheumatology Unit, Karolinska Institutet, Stockholm, Sweden, ²⁹Rheumatology, Hairmyres Hospital, East Kilbride, United Kingdom, ³⁰Universidad del Pais Vasco, Servicio de Medicina Interna, Hospital de Cruces, Bizkaia, Spain, ³¹Emory University School of Medicine, Atlanta, GA, ³²Abteilung Rheumatologie/Rehab, Kantonsspital Schaffhausen, Schaffhausen, Switzerland, ³³Department of Internal Medicine, Division of Rheumatology, Istanbul University, Istanbul Faculty of Medicine, Istanbul, Turkey, ³⁴Division of Rheumatology, Allergy & Immunology, UCSD School of Medicine Center for Innovative Therapy, La Jolla, CA, ³⁵Medicine, Medical University of South Carolina, Charleston, SC, ³⁶School of Sport, Health and Exercise Sciences, Bangor University, George Building, Bangor, Gwynedd, LL57 2PZ, UK., Bangor, United Kingdom, ³⁷Rheumatology, Univ of Manitoba, Winnipeg, MB, Canada, ³⁸Rheumatology, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, ³⁹Columbia University College of Physicians & Surgeons, New York, NY, ⁴⁰Medicine, Division of Rheumatology, New York University School of Medicine, New York, NY, ⁴¹Medicine/Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, ⁴²Department of Autoimmune Diseases, CELLEX-IDIBAPS, Hospital Clínic, Barcelona, Barcelona, Spain, ⁴³Clinical Epidemiology, Research Institute of the McGill University Health Centre, Montreal, QC, Canada, ⁴⁴Immunology/Epidemiology, Montreal General Hospital, Montreal, QC, Canada

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: ANA, autoantibodies, biomarkers and diagnosis, SLE

Session Information

Date: Sunday, November 8, 2015

Title: Systemic Lupus Erythematosus - Clinical Aspects and Treatment Poster Session I

Session Type: ACR Poster Session A

Session Time: 9:00AM-11:00AM

Background/Purpose: Autoantibodies to the nuclear autoantigen dense fine speckles 70 (DFS70) are associated with a new paradigm whereby when they are found in isolation (monospecific – no other detectable autoantibodies), they are purported to rule out the diagnosis of systemic lupus erythematosus (SLE) and other anti-nuclear antibody (ANA)-related conditions. Anti-DFS70 can be screened by indirect immunofluorescence (IIF) and quantified and confirmed by chemiluminescence immunoassay (CIA). The reported frequency of anti-DFS70 by CIA in SLE is low compared to healthy individuals (0-6% vs. 7-20%). Furthermore, anti-DFS70 monospecificity is reported to be low in SLE patients (<1%). To date, there have been no studies examining the frequency of anti-DFS70 in early inception SLE cohorts. The purpose of this study was to determine the prevalence of anti-DFS70 in newly diagnosed SLE patients and to identify any univariate associations with demographic and clinical features.

Methods: Patients fulfilling the American College of Rheumatology (ACR) Classification Criteria for SLE were enrolled in the Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. Demographic and clinical data, including disease activity (SLEDAI-2K), were collected at enrollment. ANAs were detected by IIF on HEp-2 cells (ImmunoConcepts, Sacramento, CA), and extractable nuclear antigens (ENAs) and double-stranded DNA (ds-DNA) by an addressable laser bead immunoassay (FIDIS Connective 13, TheraDiag, Paris). Anti-DFS70 antibodies were measured by CIA using cutoffs suggested by the manufacturer (Inova Diagnostics Inc., San Diego, CA).

Results: 1137 patients were included; 89.4% were female and 94.4% were ANA IIF positive (Table 1). The frequency of anti-DFS70 by CIA was 7.1% [95%CI: 5.7-8.8%] (81/1137 patients). 11/1137 (0.97%) [95%CI: 0.5-1.7%] of the entire cohort were positive for anti-DFS70 only with no detectable ENA or anti-dsDNA and were therefore considered ÔmonospecificÕ for anti-DFS70. Patients with a negative anti-DFS70 by CIA were more likely than those with a positive anti-DFS70 to have other SLE-related autoantibodies including anti-U1-RNP (31.5% vs. 21.0%), anti-Ro60 (46.3% vs. 34.6%), and anti-SSB (16.0% vs. 4.9%). Age, gender, ethnicity, disease features included in the ACR classification criteria, SLEDAI-2K score, or concomitant therapies did not differ between the anti-DFS70 negative and positive patients.

Conclusion: The prevalence of anti-DFS70 measured by CIA in newly diagnosed SLE patients was at the high end of the range as compared to that in previously published SLE cohorts (7.1% vs. 0-6%). However, “monospecific” anti-DFS70 was rare (0.97%) in this SLE inception cohort and, therefore, the presence of monospecific anti-DFS70 is a potentially useful test to discriminate between ANA positive healthy individuals and those newly diagnosed with definite SLE.

Disclosure: M. Choi, None; J. G. Hanly, None; M. Urowitz, None; J. Romero-Diaz, None; C. Gordon, None; S. C. Bae, None; S. Bernatsky, None; D. J. Wallace, None; J. T. Merrill, None; D. A. Isenberg, None; A. Rahman, None; E. M. Ginzler, None; P. R. Fortin, None; D. Gladman, None; J. Sanchez-Guerrero, None; M. Petri, None; I. N. Bruce, None; M. A. Dooley, None; R. Ramsey-Goldman, None; C. Aranow, None; G. S. Alarcon, None; K. Steinsson, None; O. Nived, None; G. K. Sturfelt, None; S. Manzi, None; M. Khamashta, None; R. F. van Vollenhoven, None; A. Zoma, None; G. Ruiz-Irastorza, None; S. S. Lim, None; T. Stoll, None; M. Inanc, None; K. C. Kalunian, None; D. L. Kamen, None; P. Maddison, None; C. A. Peschken, None; S. Jacobsen, None; A. Askanase, None; J. P. Buyon, None; W. W. Chatham, None; M. Ramos-Casals, None; Y. St. Pierre, None; A. E. Clarke, None; M. J. Fritzler, Inova Diagnostics, Inc., 5,Immuno Concepts, 5.

To cite this abstract in AMA style:

Choi M, Hanly JG, Urowitz M, Romero-Diaz J, Gordon C, Bae SC, Bernatsky S, Wallace DJ, Merrill JT, Isenberg DA, Rahman A, Ginzler EM, Fortin PR, Gladman D, Sanchez-Guerrero J, Petri M, Bruce IN, Dooley MA, Ramsey-Goldman R, Aranow C, Alarcon GS, Steinsson K, Nived O, Sturfelt GK, Manzi S, Khamashta M, van Vollenhoven RF, Zoma A, Ruiz-Irastorza G, Lim SS, Stoll T, Inanc M, Kalunian KC, Kamen DL, Maddison P, Peschken CA, Jacobsen S, Askanase A, Buyon JP, Chatham WW, Ramos-Casals M, St. Pierre Y, Clarke AE, Fritzler MJ. The Prevalence of Anti-DFS70 Antibodies in an International Inception Cohort of Systemic Lupus Erythematosus [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/the-prevalence-of-anti-dfs70-antibodies-in-an-international-inception-cohort-of-systemic-lupus-erythematosus/. Accessed .

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