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; Søren 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, Søren Jacobsen, Christine Peschken, Diane L Kamen, Anca Askanase, Jill P Buyon, Karen H Costenbader, Marvin J Fritzler

Department for Rheumatology and Spine Diseases

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
Journal	Annals of the Rheumatic Diseases
Volume	81
Issue number	8
Pages (from-to)	1143-1150
Number of pages	8
ISSN	0003-4967
DOIs	https://doi.org/10.1136/annrheumdis-2022-222168
Publication status	Published - Aug 2022

Keywords

Antibodies, Antinuclear
Autoantibodies
Cross-Sectional Studies
Fluorescent Antibody Technique, Indirect
Humans
Lupus Erythematosus, Systemic/diagnosis

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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

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, S, 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

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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 = "Antibodies, Antinuclear, Autoantibodies, Cross-Sectional Studies, Fluorescent Antibody Technique, Indirect, Humans, Lupus Erythematosus, Systemic/diagnosis",

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 S{\o}ren Jacobsen and Christine Peschken and Kamen, {Diane L} and Anca Askanase and Buyon, {Jill P} and Costenbader, {Karen H} and Fritzler, {Marvin J}",

note = "{\textcopyright} Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.",

year = "2022",

month = aug,

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

language = "English",

volume = "81",

pages = "1143--1150",

journal = "Annals of the Rheumatic Diseases",

issn = "0003-4967",

publisher = "B M J Group",

number = "8",

}

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, Søren

AU - Peschken, Christine

AU - Kamen, Diane L

AU - Askanase, Anca

AU - Buyon, Jill P

AU - Costenbader, Karen H

AU - Fritzler, Marvin J

PY - 2022/8

Y1 - 2022/8

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 - Antibodies, Antinuclear

KW - Autoantibodies

KW - Cross-Sectional Studies

KW - Fluorescent Antibody Technique, Indirect

KW - Humans

KW - Lupus Erythematosus, Systemic/diagnosis

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U2 - 10.1136/annrheumdis-2022-222168

DO - 10.1136/annrheumdis-2022-222168

M3 - Journal 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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