Dynamics of Anti-Nuclear Antibodies in a Longitudinal Study of a Large Systemic Lupus Erythematosus Cohort

May Choi¹, Marvin Fritzler², Karen Costenbader³, Murray Urowitz⁴, John Hanly⁵, Caroline Gordon⁶, Yvan St. Pierre⁷, Sang-Cheol Bae⁸, Juanita Romero-Díaz⁹, F Jorge Sanchez-Guerrero¹⁰, Sasha Bernatsky¹¹, Daniel Wallace¹², David Isenberg¹³, Anisur Rahman¹⁴, Joan Merrill¹⁵, Paul Fortin¹⁶, Dafna Gladman¹⁷, Ian Bruce¹⁸, Michelle Petri¹⁹, Ellen M Ginzler²⁰, Mary Anne Dooley²¹, Rosalind Ramsey-Goldman²², Susan Manzi²³, Andreas Jönsen²⁴, Graciela Alarcón²⁵, Ronald F Van Vollenhoven²⁶, Cynthia Aranow²⁷, Meggan Mackay²⁸, Guillermo Ruiz-Irastorza²⁹, S. Sam Lim³⁰, Murat Inanc³¹, Kenneth Kalunian³², Søren Jacobsen³³, Christine Peschken³⁴, Diane Kamen³⁵, Anca Askanase³⁶ and Ann Clarke³⁷, ¹Brigham and Women's Hospital | Cumming School of Medicine, University of Calgary, Calgary, AB, Canada, ²Department of Medicine, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada, ³Brigham and Women's Hospital and Harvard Medical School, Boston, MA, ⁴University Health Network, University of Toronto, Toronto, ON, Canada, ⁵Dalhousie University, Halifax, NS, Canada, ⁶University of Birmingham, Birmingham, England, United Kingdom, ⁷McGill University, Montreal, Canada, ⁸Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Republic of Korea, ⁹Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico City, Mexico, ¹⁰University Health Network/Sinai Health system, Toronto, ON, Canada, ¹¹The Research Institute of the McGill University Health Centre, Montreal, ON, Canada, ¹²Cedars-Sinai Medical Center/UCLA, Los Angeles, CA, ¹³Centre for Rheumatology, University College London and Department of Rheumatology, University College Hospital, London, United Kingdom, ¹⁴University College London, London, United Kingdom, ¹⁵Oklahoma Medical Research Foundation, Oklahoma City, ¹⁶CHU de Quebec - Universite Laval, Quebec, Canada, ¹⁷Krembil Research Institute, Toronto Western Hospital, Toronto, ON, Canada, ¹⁸Centre for Epidemiology Versus Arthritis, The University of Manchester and NIHR Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, United Kingdom, ¹⁹Johns Hopkins University School of Medicine, Baltimore, ²⁰SUNY Downstate Health Sciences University, Brooklyn, ²¹University of North Carolina, Chapel Hill, NC, ²²Division of Rheumatology, Northwestern University Feinberg School of Medicine, Chicago, IL, ²³Lupus Center of Excellence, Autoimmunity Institute, Allegheny Health Network, Pittsburgh, PA, ²⁴Lund University, Lund, Sweden, ²⁵Division of Clinical Immunology and Rheumatology, Department of Medicine, School of Medicine, The University of Alabama at Birmingham; Department of Medicine, School of Medicine; Universidad Peruana Cayetano, Heredia, Alabama, ²⁶Department of Rheumatology, Amsterdam Rheumatology and Immunology Center, Amsterdam, Netherlands, ²⁷Feinstein Institutes for Medical Research, Manhasset, NY, ²⁸Feinstein Institute for Medical Research, Manhasset, NY, ²⁹Hospital Universitario Cruces, Barakaldo, Spain, ³⁰Emory University, Atlanta, GA, ³¹Department of Rheumatology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Turkey, ³²University of California San Diego, La Jolla, CA, ³³University of Copenhagen, Copenhagen, Denmark, ³⁴Departments of Medicine and Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada, ³⁵Medical University of South Carolina, Charleston, SC, ³⁶Columbia University College of Physicians and Surgeons, New York, NY, ³⁷University of Calgary, Calgary, Canada

Meeting: ACR Convergence 2020

Keywords: Autoantibody(ies), Systemic lupus erythematosus (SLE)

Session Information

Date: Friday, November 6, 2020

Title: SLE – Diagnosis, Manifestations, & Outcomes Poster I: Clinical Manifestations

Session Type: Poster Session A

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

Background/Purpose: ANA testing as an approach to diagnosing and classifying SLE, now embedded in the EULAR/ACR Criteria, is more important than ever. Cross-sectional studies indicate that as few as 70% are ANA-positive, although ANA status may change over time. There are limited previous attempts to look at alterations in longitudinal ANA status in newly diagnosed SLE (1). We examined the dynamics of ANA tests in a longitudinal analysis using the SLICC Inception Cohort.

Methods: We evaluated demographic, clinical, and serological data from SLICC patients who fulfilled the 1997 Updated ACR SLE Classification Criteria and were within 15 months of diagnosis at enrolment. We performed two FDA-approved ANA tests: HEp-2 indirect immunofluorescence assay (IFA) and enzyme-linked immunosorbent assay (ELISA) (both from Inova Diagnostics, San Diego, CA) for each patient at enrolment and follow-up at years 3 and 5, at one central laboratory (Calgary, AB). A positive test was defined as a titer ≥1:80 for IFA and ≥20 units by ELISA. SLE-specific autoantibodies were performed using a commercially available autoantigen array (FIDIS Connective Profile-13, TheraDiag, Paris) in an addressable laser bead immunoassay. Anti-dsDNA positivity and titers were confirmed by chemiluminescent assay (BioFlash: Inova Diagnostics). Demographic and clinical characteristics of patients with a negative ANA test at any time point over the 5 years of disease were compared to patients with consistently positive ANA tests.

Results: Overall, 759 patients were included; 88.5% were female and the mean age at diagnosis was 35.2 (SD 13.5) years. There were 8 different ANA trajectories over 5 years; 29 (3.8%) tested negative at least once by ANA IFA and 101 (13.3%) by ELISA (Table 1). Compared to patients with a positive ANA at all 3 time points (n=644), those with any negative ANA (either IFA or ELISA, n=115) were diagnosed at an older age (37.9 vs 34.7 years), were more likely to be of white ethnicity (67.8% vs 49.8%), less likely to use steroids at enrolment (60.9% vs 71.0%), less likely to have ever used immunosuppressants/biologics at 5 years (57.4% vs 68.0%) (Table 2), and less likely to have other SLE-related antibodies at enrolment and year 5 (Table 3). The SLEDAI-2K of patients with a negative ANA (vs those with a persistently positive ANA) was lower (4.2 vs 5.9 at enrolment, 2.0 vs 3.3 at year 5) with less mucocutaneous (28.7% vs 39.0% at enrolment), immunological (38.3% vs 59.5% at enrolment and 31.3% vs 53.4% at year 5), and hematological (3.5% vs 11.8% at enrolment and 2.6% vs 10.1% at year 5) involvement.

Conclusion: Most of the 759 cases (84.8%) in the SLICC inception cohort remained ANA positive on both IFA and ELISA at each time point over the first 5 years of follow-up. The proportion of consistently ANA-positive patients was higher by IFA (96.2%) than ELISA (86.7%). Patients with at least one negative ANA over the first 5 years had features suggestive of milder disease (i.e. lower SLEDAI-2K, less steroid and immunosuppressive use, fewer autoantibodies) compared to patients with persistently positive ANAs, but differences in other disease features, e.g. nephritis and SLICC/ACR Damage Index, were not observed.

Ref: 1. Acosta-Merida A, Isenberg DA. CLIN EXP RHEUMATOL.2013;31(4):656

Disclosure: M. Choi, None; M. Fritzler, Inova Diagnostics Inc, 5, 8, Werfen International, 5, 8; K. Costenbader, Glaxo Smith Kline, 5, UpToDate, 7, Lupus Foundation of America, 6, Neutrolis Inc, 5; M. Urowitz, None; J. Hanly, None; C. Gordon, UCB, 1, 2, 3, 4, CDC, 1, MGP, 1; Y. St. Pierre, None; S. Bae, None; J. Romero-Díaz, Biogen, 5; F. Sanchez-Guerrero, None; S. Bernatsky, None; D. Wallace, None; D. Isenberg, AstraZeneca, 5, Celgene, 5, Merck Serono, 5, UCB, 5, Servier, 5; A. Rahman, None; J. Merrill, Bristol Myers Squibb, 2, 5, GlaxoSmithKline, 2, 5, AstraZeneca, 5, AbbVie, 5, Amgen, 5, Aurinia, 5, EMD Serono, 5, Remegen, 5, Janssen, 5, Provention, 5, UCB, 5; P. Fortin, None; D. Gladman, AbbVie, 2, 5, Amgen, 2, 5, Janssen, 2, 5, Novartis, 2, 5, Pfizer, 2, 5, UCB, 2, 5, Bristol-Myers Squibb, 5, Gilead, 5, Galapagos, 5, Celgene, 2, 5, Eli Lilly, 2, 5; I. Bruce, Genzyme/Sanofi, 2, GlaxoSmithKline, 2, 5, 8, Roche, 2, UCB, 2, 5, 8, Eli Lilly, 5, Merck Serono, 5, ILTOO, 5, AstraZeneca, 8; M. Petri, AbbVie, 5, Amgen, 5, AstraZeneca, 2, 5, BMS, 5, Decision Resources, 5, GSK, 2, 5, INOVA, 5, IQVIA, 5, Janssen, 5, Eli Lilly, 2, 5, Merck EMD Serono, 5, Sanofi Japan, 5, Thermofisher, 5, UCB, 5, Exagen, 2; E. Ginzler, Aurinia Pharmaceuticals, Inc., 2; M. Dooley, Bristol-Myers Squibb Company, 5, GlaxoSmithKline, 5, Aurinia, 5; R. Ramsey-Goldman, None; S. Manzi, AstraZeneca, 2, 5; A. Jönsen, None; G. Alarcón, None; R. Van Vollenhoven, BMS, 2, GlaxoSmithKline, 2, Lilly, 2, UCB, 2, 5, 8, AbbVie, 5, 8, AstraZeneca, 5, 8, Biogen, 5, Biotest, 5, Celgene, 5, Galapagos, 5, 8, Gilead, 5, Janssen, 5, 8, Pfizer, 5, 8, Servier, 5; C. Aranow, None; M. Mackay, None; G. Ruiz-Irastorza, None; S. Lim, None; M. Inanc, None; K. Kalunian, Roche, 5, Biogen, 5, Janssen, 5, AstraZeneca, 5, Lupus Research Alliance, 2, Pfizer, 2, Sanford Consortium, 2, Eli Lilly, 5, Genetech, 5, Gilead, 5, ILTOO, 5, Nektar, 5, Viela, 5, Equillium, 5, Bristol-Meyers Squibb, 5; S. Jacobsen, BMS, 2; C. Peschken, GSK, 5, Eli-Lilly, 5, Astra Zeneca, 5; D. Kamen, None; A. Askanase, GlaxoSmithKline, 2, 5, AstraZeneca, 2, 5, AbbVie, 5, Bristol Myers Squibb, 5, Janssen, 2, Eli Lilly, 2, Pfizer, 2, LuCIN, 2, Mallinckrodt Pharmaceuticals, 2; A. Clarke, AstraZenca, 5, Exagen Diagnostics, 5.

To cite this abstract in AMA style:

Choi M, Fritzler M, Costenbader K, Urowitz M, Hanly J, Gordon C, St. Pierre Y, Bae S, Romero-Díaz J, Sanchez-Guerrero F, Bernatsky S, Wallace D, Isenberg D, Rahman A, Merrill J, Fortin P, Gladman D, Bruce I, Petri M, Ginzler E, Dooley M, Ramsey-Goldman R, Manzi S, Jönsen A, Alarcón G, Van Vollenhoven R, Aranow C, Mackay M, Ruiz-Irastorza G, Lim S, Inanc M, Kalunian K, Jacobsen S, Peschken C, Kamen D, Askanase A, Clarke A. Dynamics of Anti-Nuclear Antibodies in a Longitudinal Study of a Large Systemic Lupus Erythematosus Cohort [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 10). https://acrabstracts.org/abstract/dynamics-of-anti-nuclear-antibodies-in-a-longitudinal-study-of-a-large-systemic-lupus-erythematosus-cohort/. Accessed .

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