Longitudinal analysis of ANA in the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort

• Type of Material: Article
• Authors: May Y Choi, University of Calgary; Ann E Clarke, University of Calgary; Murray Urowitz, Toronto Western Hospital; John Hanly, Queen Elizabeth II Health Sciences Centre and Dalhousie University; Yvan St-Pierre, McGill University; Caroline Gordon, University of Birmingham; Sang-Cheol Bae, Hanyang University Hospital for Rheumatic Diseases and Hanyang University Institute for Rheumatology, Seoul, Korea; Juanita Romero-Diaz, Instituto Nacional de Ciencias Médicas y Nutrición, Mexico City, Mexico; Jorge Sanchez-Guerrero, Toronto Western Hospital; Sasha Bernatsky, McGill University; Daniel J Wallace, University of California Los Angeles; David Isenberg, University College London; Anisur Rahman, University College London; Joan T Merrill, Oklahoma Medical Research Foundation; Paul R Fortin, Laval University; Dafna D Gladman, Toronto Western Hospital; Ian N Bruce, University of Manchester; Michelle Petri, Johns Hopkins University; Ellen M Ginzler, SUNY Downstate Medical Center; Mary Anne Dooley, University of North Carolina; Rosalind Ramsey-Goldman, Northwestern University; Susan Manzi, University of Pittsburgh; Andreas Jonsen, Lund University; Graciela S Alarcón, University of Alabama Birmingham; Ronald F van Vollenhoven, University of Amsterdam; Cynthia Aranow, Feinstein Institute for Medical Research, Manhasset, New York; Meggan Mackay, Feinstein Institute for Medical Research, Manhasset, New York; Guillermo Ruiz-Irastorza, University of Basque Country; Sam Lim, Emory University; Murat Inanc, Istanbul University; Kenneth Kalunian, University of California Los Angeles; Søren Jacobsen, Copenhagen University Hospital; Christine Peschken, University of Manitoba; Diane L Kamen, Medical University of South Carolina; Anca Askanase, New York University; Jill P Buyon, New York University; Karen H Costenbader, Brigham and Women’s Hospital, Harvard Medical School; Marvin J Fritzler, University of Calgary
• Language: English
• Date: 2022-03-25
• Publisher: BMJ PUBLISHING GROUP
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © Author(s) (or their employer(s)) 2022.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1136/annrheumdis-2022-222168
• Title of Journal or Parent Work: ANNALS OF THE RHEUMATIC DISEASES
• Volume: 81
• Issue: 8
• Start Page: 1143
• End Page: 1150
• Grant/Funding Information: Dr. Caroline Gordon’s work was supported by Lupus UK, Sandwell and West Birmingham Hospitals NHS Trust and the NIHR /Wellcome Trust Clinical Research Facility in Birmingham.; Dr. May Choi is supported by the Lupus Foundation of America Gary S. Gilkeson Career Development Award and research gifts in kind from MitogenDx (Calgary, Canada).; The cost of the immunoassay supplies and labor were supported by the Lupus Foundation of America and MitogenDx.; Dr. Ruiz-Irastorza is supported by the Department of Education, Universities and Research of the Basque Government.; Dr. Paul R. Fortin presently holds a tier 1 Canada Research Chair on Systemic Autoimmune Rheumatic Diseases at Université Laval, and part of this work was done while he was still holding a Distinguished Senior Investigator of The Arthritis Society.; Dr. Mary Anne Dooley’s work was supported by the NIH grant RR00046.; Dr. Ramsey-Goldman’s work was supported by the NIH (grants 1U54TR001353 formerly 8UL1TR000150 and UL-1RR-025741, K24-AR-02318, and P60AR064464 formerly P60-AR-48098).; Dr. Hanly’s work was supported by the Canadian Institutes of Health Research (research grant MOP-88526).; Dr. Soren Jacobsen is supported by the Danish Rheumatism Association (A1028) and the Novo Nordisk Foundation (A05990).; Dr. Clarke holds The Arthritis Society Research Chair in Rheumatic Diseases at the University of Calgary.; Dr. Susan Manzi is supported by grants R01 AR046588 and K24 AR002213; Dr. Sang-Cheol Bae’s work was supported by the Korea Healthcare technology R & D project, Ministry for Health and Welfare, Republic of Korea (A120404).; The Montreal General Hospital Lupus Clinic is partially supported by the Singer Family Fund for Lupus Research.; Dr. Rahman and Dr. Isenberg are supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre.; Dr. Bruce is an NIHR Senior Investigator Emeritus and is funded by the National Institute for Health Research Manchester Biomedical Research Centre and the NIHR/Wellcome Trust Manchester Clinical Research Facility. The views expressed in this publication are those of the author(s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health.; Dr. Costenbader is supported by NIH K24 AR066109.; The Hopkins Lupus Cohort is supported by NIH Grants AR043727 and AR069572
• Keywords: FLUCTUATION; DISEASE-ACTIVITY; Science & Technology; ONSET; Systemic Lupus Erythematosus; CRITERIA; SM; ANTINUCLEAR ANTIBODIES; Autoimmunity; SEROCONVERSION; Life Sciences & Biomedicine; ERYTHEMATOSUS; Rheumatology; Autoantibodies

Abstract

Objectives A perception derived from cross-sectional studies of small systemic lupus erythematosus (SLE) cohorts is that there is a marked discrepancy between antinuclear antibody (ANA) assays, which impacts on clinicians' approach to diagnosis and follow-up. We compared three ANA assays in a longitudinal analysis of a large international incident SLE cohort retested regularly and followed for 5 years. Methods Demographic, clinical and serological data was from 805 SLE patients at enrolment, year 3 and 5. Two HEp-2 indirect immunofluorescence assays (IFA1, IFA2), an ANA ELISA, and SLE-related autoantibodies were performed in one laboratory. Frequencies of positivity, titres or absorbance units (AU), and IFA patterns were compared using McNemar, Wilcoxon and kappa statistics, respectively. Results At enrolment, ANA positivity (≥1:80) was 96.1% by IFA1 (median titre 1:1280 (IQR 1:640-1:5120)), 98.3% by IFA2 (1:2560 (IQR 1:640-1:5120)) and 96.6% by ELISA (176.3 AU (IQR 106.4 AU-203.5 AU)). At least one ANA assay was positive for 99.6% of patients at enrolment. At year 5, ANA positivity by IFAs (IFA1 95.2%; IFA2 98.9%) remained high, while there was a decrease in ELISA positivity (91.3%, p<0.001). Overall, there was >91% agreement in ANA positivity at all time points and ≥71% agreement in IFA patterns between IFA1 and IFA2. Conclusion In recent-onset SLE, three ANA assays demonstrated commutability with a high proportion of positivity and titres or AU. However, over 5 years follow-up, there was modest variation in ANA assay performance. In clinical situations where the SLE diagnosis is being considered, a negative test by either the ELISA or HEp-2 IFA may require reflex testing.