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

May Yee Choi; Ann Elaine Clarke; Murray Urowitz; John Hanly; Yvan St-Pierre; Caroline Gordon; Sang-Cheol Bae; Juanita Romero-Diaz; Jorge Sanchez-Guerrero; Sasha Bernatsky; Daniel J. Wallace; David Isenberg; Anisur Rahman; Joan T. Merrill; Paul R. Fortin; Dafna D. Gladman; Ian N. Bruce; Michelle Petri; Ellen M. Ginzler; Mary Anne Dooley; Rosalind Ramsey-Goldman; Susan Manzi; Andreas Jönsen; Graciela S. Alarcón; Ronald F. van Vollenhoven; Cynthia Aranow; Meggan Mackay; Guillermo Ruiz-Irastorza; Sam Lim; Murat Inanc; Ken Kalunian; S. ren Jacobsen; Christine Peschken; Diane L. Kamen; Anca Askanase; Jill P. Buyon; Karen H. Costenbader; Marvin J. Fritzler

doi:10.1136/annrheumdis-2022-222168

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

May Yee Choi, Ann Elaine Clarke, Murray Urowitz, John Hanly, Yvan St-Pierre, Caroline Gordon, Sang-Cheol Bae, Juanita Romero-Diaz, Jorge Sanchez-Guerrero, Sasha Bernatsky, Daniel J. Wallace, David Isenberg, Anisur Rahman, Joan T. Merrill, Paul R. Fortin, Dafna D. Gladman, Ian N. Bruce, Michelle Petri, Ellen M. Ginzler, Mary Anne DooleyRosalind Ramsey-Goldman, Susan Manzi, Andreas Jönsen, Graciela S. Alarcón, Ronald F. van Vollenhoven, Cynthia Aranow, Meggan Mackay, Guillermo Ruiz-Irastorza, Sam Lim, Murat Inanc, Ken Kalunian, S. ren Jacobsen, Christine Peschken, Diane L. Kamen, Anca Askanase, Jill P. Buyon, Karen H. Costenbader, Marvin J. Fritzler

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	1143-1150
Number of pages	8
Journal	Annals of the Rheumatic Diseases
Volume	81
Issue number	8
DOIs	https://doi.org/10.1136/annrheumdis-2022-222168
Publication status	Published - 1 Aug 2022

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10.1136/annrheumdis-2022-222168

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Choi, M. Y., Clarke, A. E., Urowitz, M., Hanly, J., St-Pierre, Y., Gordon, C., Bae, S-C., Romero-Diaz, J., Sanchez-Guerrero, J., Bernatsky, S., Wallace, D. J., Isenberg, D., Rahman, A., Merrill, J. T., Fortin, P. R., Gladman, D. D., Bruce, I. N., Petri, M., Ginzler, E. M., ... Fritzler, M. J. (2022). Longitudinal analysis of ANA in the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort. Annals of the Rheumatic Diseases, 81(8), 1143-1150. https://doi.org/10.1136/annrheumdis-2022-222168

@article{d5588abaf5e849769a8322e6af2bd5a6,

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

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.",

keywords = "Autoantibodies, Autoimmunity, Systemic Lupus Erythematosus",

author = "Choi, {May Yee} and Clarke, {Ann Elaine} and Murray Urowitz and John Hanly and Yvan St-Pierre and Caroline Gordon and Sang-Cheol Bae and Juanita Romero-Diaz and Jorge Sanchez-Guerrero and Sasha Bernatsky and Wallace, {Daniel J.} and David Isenberg and Anisur Rahman and Merrill, {Joan T.} and Fortin, {Paul R.} and Gladman, {Dafna D.} and Bruce, {Ian N.} and Michelle Petri and Ginzler, {Ellen M.} and Dooley, {Mary Anne} and Rosalind Ramsey-Goldman and Susan Manzi and Andreas J{\"o}nsen and Alarc{\'o}n, {Graciela S.} and {van Vollenhoven}, {Ronald F.} and Cynthia Aranow and Meggan Mackay and Guillermo Ruiz-Irastorza and Sam Lim and Murat Inanc and Ken Kalunian and Jacobsen, {S. ren} and Christine Peschken and Kamen, {Diane L.} and Anca Askanase and Buyon, {Jill P.} and Costenbader, {Karen H.} and Fritzler, {Marvin J.}",

note = "Funding Information: The cost of the immunoassay supplies and labor were supported by the Lupus Foundation of America and MitogenDx. MYC is supported by the Lupus Foundation of America Gary S. Gilkeson Career Development Award and research gifts in kind from MitogenDx (Calgary, Canada). AEC holds The Arthritis Society Research Chair in Rheumatic Diseases at the University of Calgary. KHC is supported by NIH K24 AR066109. JH work was supported by the Canadian Institutes of Health Research (research grant MOP-88526). CG work was supported by Lupus UK, Sandwell and West Birmingham Hospitals NHS Trust and the NIHR /Wellcome Trust Clinical Research Facility in Birmingham. S-CB 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. AR and DI are supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The Hopkins Lupus Cohort is supported by NIH Grants AR043727 and AR069572. PRF presently holds a tier 1 Canada Research Chair on Systemic Autoimmune Rheumatic Diseases at Universit{\'e} Laval, and part of this work was done while he was still holding a Distinguished Senior Investigator of The Arthritis Society. INB 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. MAD work was supported by the NIH grant RR00046. RR-G work was supported by the NIH (grants 1U54TR001353 formerly 8UL1TR000150 and UL-1RR-025741, K24-AR-02318, and P60AR064464 formerly P60-AR-48098). SM is supported by grants R01 AR046588 and K24 AR002213 GR-I is supported by the Department of Education, Universities and Research of the Basque Government. SJ is supported by the Danish Rheumatism Association (A1028) and the Novo Nordisk Foundation (A05990). Funding Information: MYC has received consulting fees from Janssen and MitogenDx (less than US$10 000). AEC has received consulting fees from AstraZeneca, BristolMyersSquibb, and Glaxo Smith Kline (less than US$10 000 each). KCH has consulted for or collaborated on research projects with Janssen, Glaxo Smith Kline, Exagen Diagnostics, Eli Lilly, Merck Serono, Astra Zeneca and Neutrolis (less than US$10 000 each). CG has received consulting fees, speaking fees, and/or honoraria from AstraZeneca, Abbvie, Amgen, UCB, GlaxoSmithKline, Merck Serono and BMS (less than US$10 000 each) and grants from UCB. Grants from UCB were not to CG but to Sandwell and West Birmingham Hospitals NHS Trust. DDG received consulting fees, speaking fees, and/or honoraria from GlaxoSmithKline (less than $10 000). INB has received consulting fees, speaking fees and/or honoraria from Eli Lilly, UCB, Roche, Merck Serono, MedImmune (less than US$10 000 each) and grants from UCB, Genzyme Sanofi and GlaxoSmithKline. EMG has paid consultation with investment analysts Guidepoint Global Gerson Lerman Group.Dr. Kalunian has received grants from UCB, Human Genome Sciences/GlaxoSmithKline, Takeda, Ablynx, Bristol-Myers Squibb, Pfizer and Kyowa Hakko Kirin, and has received consulting fees from Exagen Diagnostics, Genentech, Eli Lilly, Bristol-Myers Squibb, and Anthera (less than US$10 000 each). MJF is Director of Mitogen Diagnostics Corporation (Calgary, AB Canada) and a consultant to Werfen International (Barcelona, Spain), Grifols (Barcelona, Spain), Janssen Pharmaceuticals of Johnson & Johnson and Alexion Canada (less than US$10 000 each). The remainder of the authors have no disclosures. Publisher Copyright: {\textcopyright} Author(s) (or their employer(s)) 2022.",

year = "2022",

month = aug,

day = "1",

doi = "10.1136/annrheumdis-2022-222168",

language = "English",

volume = "81",

pages = "1143--1150",

journal = "Annals of the Rheumatic Diseases",

issn = "0003-4967",

publisher = "BMJ Publishing Group",

number = "8",

}

Choi, MY, Clarke, AE, Urowitz, M, Hanly, J, St-Pierre, Y, Gordon, C, Bae, S-C, Romero-Diaz, J, Sanchez-Guerrero, J, Bernatsky, S, Wallace, DJ, Isenberg, D, Rahman, A, Merrill, JT, Fortin, PR, Gladman, DD, Bruce, IN, Petri, M, Ginzler, EM, Dooley, MA, Ramsey-Goldman, R, Manzi, S, Jönsen, A, Alarcón, GS, van Vollenhoven, RF, Aranow, C, Mackay, M, Ruiz-Irastorza, G, Lim, S, Inanc, M, Kalunian, K, Jacobsen, SR, Peschken, C, Kamen, DL, Askanase, A, Buyon, JP, Costenbader, KH & Fritzler, MJ 2022, 'Longitudinal analysis of ANA in the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort', Annals of the Rheumatic Diseases, vol. 81, no. 8, pp. 1143-1150. https://doi.org/10.1136/annrheumdis-2022-222168

TY - JOUR

T1 - Longitudinal analysis of ANA in the Systemic Lupus International Collaborating Clinics (SLICC) Inception Cohort

AU - Choi, May Yee

AU - Clarke, Ann Elaine

AU - Urowitz, Murray

AU - Hanly, John

AU - St-Pierre, Yvan

AU - Gordon, Caroline

AU - Bae, Sang-Cheol

AU - Romero-Diaz, Juanita

AU - Sanchez-Guerrero, Jorge

AU - Bernatsky, Sasha

AU - Wallace, Daniel J.

AU - Isenberg, David

AU - Rahman, Anisur

AU - Merrill, Joan T.

AU - Fortin, Paul R.

AU - Gladman, Dafna D.

AU - Bruce, Ian N.

AU - Petri, Michelle

AU - Ginzler, Ellen M.

AU - Dooley, Mary Anne

AU - Ramsey-Goldman, Rosalind

AU - Manzi, Susan

AU - Jönsen, Andreas

AU - Alarcón, Graciela S.

AU - van Vollenhoven, Ronald F.

AU - Aranow, Cynthia

AU - Mackay, Meggan

AU - Ruiz-Irastorza, Guillermo

AU - Lim, Sam

AU - Inanc, Murat

AU - Kalunian, Ken

AU - Jacobsen, S. ren

AU - Peschken, Christine

AU - Kamen, Diane L.

AU - Askanase, Anca

AU - Buyon, Jill P.

AU - Costenbader, Karen H.

AU - Fritzler, Marvin J.

N1 - Funding Information: The cost of the immunoassay supplies and labor were supported by the Lupus Foundation of America and MitogenDx. MYC is supported by the Lupus Foundation of America Gary S. Gilkeson Career Development Award and research gifts in kind from MitogenDx (Calgary, Canada). AEC holds The Arthritis Society Research Chair in Rheumatic Diseases at the University of Calgary. KHC is supported by NIH K24 AR066109. JH work was supported by the Canadian Institutes of Health Research (research grant MOP-88526). CG work was supported by Lupus UK, Sandwell and West Birmingham Hospitals NHS Trust and the NIHR /Wellcome Trust Clinical Research Facility in Birmingham. S-CB 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. AR and DI are supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. The Hopkins Lupus Cohort is supported by NIH Grants AR043727 and AR069572. PRF 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. INB 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. MAD work was supported by the NIH grant RR00046. RR-G work was supported by the NIH (grants 1U54TR001353 formerly 8UL1TR000150 and UL-1RR-025741, K24-AR-02318, and P60AR064464 formerly P60-AR-48098). SM is supported by grants R01 AR046588 and K24 AR002213 GR-I is supported by the Department of Education, Universities and Research of the Basque Government. SJ is supported by the Danish Rheumatism Association (A1028) and the Novo Nordisk Foundation (A05990). Funding Information: MYC has received consulting fees from Janssen and MitogenDx (less than US$10 000). AEC has received consulting fees from AstraZeneca, BristolMyersSquibb, and Glaxo Smith Kline (less than US$10 000 each). KCH has consulted for or collaborated on research projects with Janssen, Glaxo Smith Kline, Exagen Diagnostics, Eli Lilly, Merck Serono, Astra Zeneca and Neutrolis (less than US$10 000 each). CG has received consulting fees, speaking fees, and/or honoraria from AstraZeneca, Abbvie, Amgen, UCB, GlaxoSmithKline, Merck Serono and BMS (less than US$10 000 each) and grants from UCB. Grants from UCB were not to CG but to Sandwell and West Birmingham Hospitals NHS Trust. DDG received consulting fees, speaking fees, and/or honoraria from GlaxoSmithKline (less than $10 000). INB has received consulting fees, speaking fees and/or honoraria from Eli Lilly, UCB, Roche, Merck Serono, MedImmune (less than US$10 000 each) and grants from UCB, Genzyme Sanofi and GlaxoSmithKline. EMG has paid consultation with investment analysts Guidepoint Global Gerson Lerman Group.Dr. Kalunian has received grants from UCB, Human Genome Sciences/GlaxoSmithKline, Takeda, Ablynx, Bristol-Myers Squibb, Pfizer and Kyowa Hakko Kirin, and has received consulting fees from Exagen Diagnostics, Genentech, Eli Lilly, Bristol-Myers Squibb, and Anthera (less than US$10 000 each). MJF is Director of Mitogen Diagnostics Corporation (Calgary, AB Canada) and a consultant to Werfen International (Barcelona, Spain), Grifols (Barcelona, Spain), Janssen Pharmaceuticals of Johnson & Johnson and Alexion Canada (less than US$10 000 each). The remainder of the authors have no disclosures. Publisher Copyright: © Author(s) (or their employer(s)) 2022.

PY - 2022/8/1

Y1 - 2022/8/1

N2 - 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.

AB - 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.

KW - Autoantibodies

KW - Autoimmunity

KW - Systemic Lupus Erythematosus

UR - http://www.scopus.com/inward/record.url?scp=85134226098&partnerID=8YFLogxK

U2 - 10.1136/annrheumdis-2022-222168

DO - 10.1136/annrheumdis-2022-222168

M3 - Article

C2 - 35338033

SN - 0003-4967

VL - 81

SP - 1143

EP - 1150

JO - Annals of the Rheumatic Diseases

JF - Annals of the Rheumatic Diseases

IS - 8

ER -

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

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