Antinuclear Antibody–Negative Systemic Lupus Erythematosus in an International Inception Cohort

May Y. Choi; Ann E. Clarke; Yvan St. Pierre; John G. Hanly; Murray B. Urowitz; Juanita Romero-Diaz; Caroline Gordon; Sang Cheol Bae; Sasha Bernatsky; Daniel J. Wallace; Joan T. Merrill; David A. Isenberg; Anisur Rahman; Ellen M. Ginzler; Michelle Petri; Ian N. Bruce; Mary A. Dooley; Paul R. Fortin; Dafna D. Gladman; Jorge Sanchez-Guerrero; Kristjan Steinsson; Rosalind Ramsey-Goldman; Munther A. Khamashta; Cynthia Aranow; Graciela S. Alarcón; Susan Manzi; Ola Nived; Asad A. Zoma; Ronald F. van Vollenhoven; Manuel Ramos-Casals; Guillermo Ruiz-Irastorza; S. Sam Lim; Kenneth C. Kalunian; Murat Inanc; Diane L. Kamen; Christine A. Peschken; Soren Jacobsen; Anca Askanase; Thomas Stoll; Jill Buyon; Michael Mahler; Marvin J. Fritzler

doi:10.1002/acr.23712

Antinuclear Antibody–Negative Systemic Lupus Erythematosus in an International Inception Cohort

May Y. Choi, Ann E. Clarke^*, Yvan St. Pierre, John G. Hanly, Murray B. Urowitz, Juanita Romero-Diaz, Caroline Gordon, Sang Cheol Bae, Sasha Bernatsky, Daniel J. Wallace, Joan T. Merrill, David A. Isenberg, Anisur Rahman, Ellen M. Ginzler, Michelle Petri, Ian N. Bruce, Mary A. Dooley, Paul R. Fortin, Dafna D. Gladman, Jorge Sanchez-GuerreroKristjan Steinsson, Rosalind Ramsey-Goldman, Munther A. Khamashta, Cynthia Aranow, Graciela S. Alarcón, Susan Manzi, Ola Nived, Asad A. Zoma, Ronald F. van Vollenhoven, Manuel Ramos-Casals, Guillermo Ruiz-Irastorza, S. Sam Lim, Kenneth C. Kalunian, Murat Inanc, Diane L. Kamen, Christine A. Peschken, Soren Jacobsen, Anca Askanase, Thomas Stoll, Jill Buyon, Michael Mahler, Marvin J. Fritzler

^*Corresponding author for this work

Medicine, Rheumatology Division

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

76 Scopus citations

Abstract

Objective: The spectrum of antinuclear antibodies (ANAs) is changing to include both nuclear staining as well as cytoplasmic and mitotic cell patterns (CMPs) and accordingly a change is occurring in terminology to anticellular antibodies. This study examined the prevalence of indirect immunofluorescence (IIF) anticellular antibody staining using the Systemic Lupus International Collaborating Clinics inception cohort. Methods: Anticellular antibodies were detected by IIF on HEp-2000 substrate using the baseline serum. Three serologic subsets were examined: ANA positive (presence of either nuclear or mixed nuclear/CMP staining), anticellular antibody negative (absence of any intracellular staining), and isolated CMP staining. The odds of being anticellular antibody negative versus ANA or isolated CMP positive was assessed by multivariable analysis. Results: A total of 1,137 patients were included; 1,049 (92.3%) were ANA positive, 71 (6.2%) were anticellular antibody negative, and 17 (1.5%) had an isolated CMP. The isolated CMP–positive group did not differ from the ANA-positive or anticellular antibody–negative groups in clinical, demographic, or serologic features. Patients who were older (odds ratio [OR] 1.02 [95% confidence interval (95% CI) 1.00, 1.04]), of white race/ethnicity (OR 3.53 [95% CI 1.77, 7.03]), or receiving high-dose glucocorticoids at or prior to enrollment (OR 2.39 [95% CI 1.39, 4.12]) were more likely to be anticellular antibody negative. Patients on immunosuppressants (OR 0.35 [95% CI 0.19, 0.64]) or with anti-SSA/Ro 60 (OR 0.41 [95% CI 0.23, 0.74]) or anti–U1 RNP (OR 0.43 [95% CI 0.20, 0.93]) were less likely to be anticellular antibody negative. Conclusion: In newly diagnosed systemic lupus erythematosus, 6.2% of patients were anticellular antibody negative, and 1.5% had an isolated CMP. The prevalence of anticellular antibody–negative systemic lupus erythematosus will likely decrease as emerging nomenclature guidelines recommend that non-nuclear patterns should also be reported as a positive ANA.

Original language	English (US)
Pages (from-to)	893-902
Number of pages	10
Journal	Arthritis Care and Research
Volume	71
Issue number	7
DOIs	https://doi.org/10.1002/acr.23712
State	Published - Jul 2019

Funding

1U54-TR-001353 [formerly 8UL1-TR-000150], UL-1RR-025741, K24-AR-02318, and P60AR064464 [formerly P60-AR-48098]). Dr. Ruiz-阀rastorza’s work was supported by the Department of Education, Universities, and Research of the Basque Government. 1May Y. Choi, MD, Ann E. Clarke, MD, MSc, Marvin J. Fritzler, PhD, MD: University of Calgary, Cumming School of Medicine, Calgary, Alberta, Canada; 2Yvan St. Pierre, MSc, Sasha Bernatsky, MD, PhD: McGill University Health Centre, Montreal, Quebec, Canada; 3John G. Hanly, MD: Queen Elizabeth 阃阀 Health Sciences Centre and Dalhousie University, Halifax, Nova Scotia, Canada; 4Murray B. Urowitz, MD, Dafna D. Gladman, MD: Toronto Western Hospital, University of Toronto, Toronto, Ontario, Canada; 5Juanita Romero-Diaz, MD, MS: 阀nstituto Nacional de Ciencias Médicas y Nutrición, Mexico City, Mexico; 6Caroline Gordon, MD: University of Birmingham, Birmingham, UK; 7Sang-Cheol Bae, MD, PhD, MPH: Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea; 8Daniel J. Wallace, MD: Cedars-Sinai/David Ge 贀en School of Medicine at University of California The views expressed herein are those of the authors and not necessarily those of the NHS, the N 阀HR, or the Department of Health, UK. The authors thank Ms. Haiyan Hou and Meifeng Zhang (Mitogen Advanced Diagnostics, University of Calgary) for technical assistance. The Montreal General Hospital Lupus Clinic is supported by the Singer Family Fund for Lupus Research. The Hopkins Lupus Cohort is supported by the N 阀H (grants AR-043727 and AR-069572). Dr. Hanly’s work was supported by the Canadian 阀nstitutes of Health Research (grant MOP-88526). Dr. Gordon’s work was supported by Lupus UK, Sandwell and West Birmingham Hospitals NHS Trust, and the N 阀HR/Wellcome Trust Clinical Research Facility in Birmingham. Dr. Bae’s work was supported by the Korea Healthcare technology R&D project, Ministry for Health and Welfare (A120404). Dr. 阀senberg’s and Dr. Rahman’s work was supported by the N 阀HR University College London Hospitals Biomedical Research Centre. Dr. Bruce’s work was supported by Arthritis Research UK, the N 阀HR Manchester Biomedical Research Centre, and the N 阀HR/Wellcome Trust Manchester Clinical Research Facility. Dr. Dooley’s work was supported by the N 阀H (grant RR-00046). Dr. Ramsey-Goldman’s work was supported by the N 阀H (grants

ASJC Scopus subject areas

Rheumatology

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Choi, M. Y., Clarke, A. E., St. Pierre, Y., Hanly, J. G., Urowitz, M. B., Romero-Diaz, J., Gordon, C., Bae, S. C., Bernatsky, S., Wallace, D. J., Merrill, J. T., Isenberg, D. A., Rahman, A., Ginzler, E. M., Petri, M., Bruce, I. N., Dooley, M. A., Fortin, P. R., Gladman, D. D., ... Fritzler, M. J. (2019). Antinuclear Antibody–Negative Systemic Lupus Erythematosus in an International Inception Cohort. Arthritis Care and Research, 71(7), 893-902. https://doi.org/10.1002/acr.23712

@article{0d500b75730048c5a40d7729b5265233,

title = "Antinuclear Antibody–Negative Systemic Lupus Erythematosus in an International Inception Cohort",

abstract = "Objective: The spectrum of antinuclear antibodies (ANAs) is changing to include both nuclear staining as well as cytoplasmic and mitotic cell patterns (CMPs) and accordingly a change is occurring in terminology to anticellular antibodies. This study examined the prevalence of indirect immunofluorescence (IIF) anticellular antibody staining using the Systemic Lupus International Collaborating Clinics inception cohort. Methods: Anticellular antibodies were detected by IIF on HEp-2000 substrate using the baseline serum. Three serologic subsets were examined: ANA positive (presence of either nuclear or mixed nuclear/CMP staining), anticellular antibody negative (absence of any intracellular staining), and isolated CMP staining. The odds of being anticellular antibody negative versus ANA or isolated CMP positive was assessed by multivariable analysis. Results: A total of 1,137 patients were included; 1,049 (92.3%) were ANA positive, 71 (6.2%) were anticellular antibody negative, and 17 (1.5%) had an isolated CMP. The isolated CMP–positive group did not differ from the ANA-positive or anticellular antibody–negative groups in clinical, demographic, or serologic features. Patients who were older (odds ratio [OR] 1.02 [95% confidence interval (95% CI) 1.00, 1.04]), of white race/ethnicity (OR 3.53 [95% CI 1.77, 7.03]), or receiving high-dose glucocorticoids at or prior to enrollment (OR 2.39 [95% CI 1.39, 4.12]) were more likely to be anticellular antibody negative. Patients on immunosuppressants (OR 0.35 [95% CI 0.19, 0.64]) or with anti-SSA/Ro 60 (OR 0.41 [95% CI 0.23, 0.74]) or anti–U1 RNP (OR 0.43 [95% CI 0.20, 0.93]) were less likely to be anticellular antibody negative. Conclusion: In newly diagnosed systemic lupus erythematosus, 6.2% of patients were anticellular antibody negative, and 1.5% had an isolated CMP. The prevalence of anticellular antibody–negative systemic lupus erythematosus will likely decrease as emerging nomenclature guidelines recommend that non-nuclear patterns should also be reported as a positive ANA.",

author = "Choi, {May Y.} and Clarke, {Ann E.} and {St. Pierre}, Yvan and Hanly, {John G.} and Urowitz, {Murray B.} and Juanita Romero-Diaz and Caroline Gordon and Bae, {Sang Cheol} and Sasha Bernatsky and Wallace, {Daniel J.} and Merrill, {Joan T.} and Isenberg, {David A.} and Anisur Rahman and Ginzler, {Ellen M.} and Michelle Petri and Bruce, {Ian N.} and Dooley, {Mary A.} and Fortin, {Paul R.} and Gladman, {Dafna D.} and Jorge Sanchez-Guerrero and Kristjan Steinsson and Rosalind Ramsey-Goldman and Khamashta, {Munther A.} and Cynthia Aranow and Alarc{\'o}n, {Graciela S.} and Susan Manzi and Ola Nived and Zoma, {Asad A.} and {van Vollenhoven}, {Ronald F.} and Manuel Ramos-Casals and Guillermo Ruiz-Irastorza and Lim, {S. Sam} and Kalunian, {Kenneth C.} and Murat Inanc and Kamen, {Diane L.} and Peschken, {Christine A.} and Soren Jacobsen and Anca Askanase and Thomas Stoll and Jill Buyon and Michael Mahler and Fritzler, {Marvin J.}",

note = "Publisher Copyright: {\textcopyright} 2018, American College of Rheumatology",

year = "2019",

month = jul,

doi = "10.1002/acr.23712",

language = "English (US)",

volume = "71",

pages = "893--902",

journal = "Arthritis Care and Research",

issn = "2151-464X",

publisher = "John Wiley and Sons Inc.",

number = "7",

}

Choi, MY, Clarke, AE, St. Pierre, Y, Hanly, JG, Urowitz, MB, Romero-Diaz, J, Gordon, C, Bae, SC, Bernatsky, S, Wallace, DJ, Merrill, JT, Isenberg, DA, Rahman, A, Ginzler, EM, Petri, M, Bruce, IN, Dooley, MA, Fortin, PR, Gladman, DD, Sanchez-Guerrero, J, Steinsson, K, Ramsey-Goldman, R, Khamashta, MA, Aranow, C, Alarcón, GS, Manzi, S, Nived, O, Zoma, AA, van Vollenhoven, RF, Ramos-Casals, M, Ruiz-Irastorza, G, Lim, SS, Kalunian, KC, Inanc, M, Kamen, DL, Peschken, CA, Jacobsen, S, Askanase, A, Stoll, T, Buyon, J, Mahler, M & Fritzler, MJ 2019, 'Antinuclear Antibody–Negative Systemic Lupus Erythematosus in an International Inception Cohort', Arthritis Care and Research, vol. 71, no. 7, pp. 893-902. https://doi.org/10.1002/acr.23712

TY - JOUR

T1 - Antinuclear Antibody–Negative Systemic Lupus Erythematosus in an International Inception Cohort

AU - Choi, May Y.

AU - Clarke, Ann E.

AU - St. Pierre, Yvan

AU - Hanly, John G.

AU - Urowitz, Murray B.

AU - Romero-Diaz, Juanita

AU - Gordon, Caroline

AU - Bae, Sang Cheol

AU - Bernatsky, Sasha

AU - Wallace, Daniel J.

AU - Merrill, Joan T.

AU - Isenberg, David A.

AU - Rahman, Anisur

AU - Ginzler, Ellen M.

AU - Petri, Michelle

AU - Bruce, Ian N.

AU - Dooley, Mary A.

AU - Fortin, Paul R.

AU - Gladman, Dafna D.

AU - Sanchez-Guerrero, Jorge

AU - Steinsson, Kristjan

AU - Ramsey-Goldman, Rosalind

AU - Khamashta, Munther A.

AU - Aranow, Cynthia

AU - Alarcón, Graciela S.

AU - Manzi, Susan

AU - Nived, Ola

AU - Zoma, Asad A.

AU - van Vollenhoven, Ronald F.

AU - Ramos-Casals, Manuel

AU - Ruiz-Irastorza, Guillermo

AU - Lim, S. Sam

AU - Kalunian, Kenneth C.

AU - Inanc, Murat

AU - Kamen, Diane L.

AU - Peschken, Christine A.

AU - Jacobsen, Soren

AU - Askanase, Anca

AU - Stoll, Thomas

AU - Buyon, Jill

AU - Mahler, Michael

AU - Fritzler, Marvin J.

PY - 2019/7

Y1 - 2019/7

N2 - Objective: The spectrum of antinuclear antibodies (ANAs) is changing to include both nuclear staining as well as cytoplasmic and mitotic cell patterns (CMPs) and accordingly a change is occurring in terminology to anticellular antibodies. This study examined the prevalence of indirect immunofluorescence (IIF) anticellular antibody staining using the Systemic Lupus International Collaborating Clinics inception cohort. Methods: Anticellular antibodies were detected by IIF on HEp-2000 substrate using the baseline serum. Three serologic subsets were examined: ANA positive (presence of either nuclear or mixed nuclear/CMP staining), anticellular antibody negative (absence of any intracellular staining), and isolated CMP staining. The odds of being anticellular antibody negative versus ANA or isolated CMP positive was assessed by multivariable analysis. Results: A total of 1,137 patients were included; 1,049 (92.3%) were ANA positive, 71 (6.2%) were anticellular antibody negative, and 17 (1.5%) had an isolated CMP. The isolated CMP–positive group did not differ from the ANA-positive or anticellular antibody–negative groups in clinical, demographic, or serologic features. Patients who were older (odds ratio [OR] 1.02 [95% confidence interval (95% CI) 1.00, 1.04]), of white race/ethnicity (OR 3.53 [95% CI 1.77, 7.03]), or receiving high-dose glucocorticoids at or prior to enrollment (OR 2.39 [95% CI 1.39, 4.12]) were more likely to be anticellular antibody negative. Patients on immunosuppressants (OR 0.35 [95% CI 0.19, 0.64]) or with anti-SSA/Ro 60 (OR 0.41 [95% CI 0.23, 0.74]) or anti–U1 RNP (OR 0.43 [95% CI 0.20, 0.93]) were less likely to be anticellular antibody negative. Conclusion: In newly diagnosed systemic lupus erythematosus, 6.2% of patients were anticellular antibody negative, and 1.5% had an isolated CMP. The prevalence of anticellular antibody–negative systemic lupus erythematosus will likely decrease as emerging nomenclature guidelines recommend that non-nuclear patterns should also be reported as a positive ANA.

AB - Objective: The spectrum of antinuclear antibodies (ANAs) is changing to include both nuclear staining as well as cytoplasmic and mitotic cell patterns (CMPs) and accordingly a change is occurring in terminology to anticellular antibodies. This study examined the prevalence of indirect immunofluorescence (IIF) anticellular antibody staining using the Systemic Lupus International Collaborating Clinics inception cohort. Methods: Anticellular antibodies were detected by IIF on HEp-2000 substrate using the baseline serum. Three serologic subsets were examined: ANA positive (presence of either nuclear or mixed nuclear/CMP staining), anticellular antibody negative (absence of any intracellular staining), and isolated CMP staining. The odds of being anticellular antibody negative versus ANA or isolated CMP positive was assessed by multivariable analysis. Results: A total of 1,137 patients were included; 1,049 (92.3%) were ANA positive, 71 (6.2%) were anticellular antibody negative, and 17 (1.5%) had an isolated CMP. The isolated CMP–positive group did not differ from the ANA-positive or anticellular antibody–negative groups in clinical, demographic, or serologic features. Patients who were older (odds ratio [OR] 1.02 [95% confidence interval (95% CI) 1.00, 1.04]), of white race/ethnicity (OR 3.53 [95% CI 1.77, 7.03]), or receiving high-dose glucocorticoids at or prior to enrollment (OR 2.39 [95% CI 1.39, 4.12]) were more likely to be anticellular antibody negative. Patients on immunosuppressants (OR 0.35 [95% CI 0.19, 0.64]) or with anti-SSA/Ro 60 (OR 0.41 [95% CI 0.23, 0.74]) or anti–U1 RNP (OR 0.43 [95% CI 0.20, 0.93]) were less likely to be anticellular antibody negative. Conclusion: In newly diagnosed systemic lupus erythematosus, 6.2% of patients were anticellular antibody negative, and 1.5% had an isolated CMP. The prevalence of anticellular antibody–negative systemic lupus erythematosus will likely decrease as emerging nomenclature guidelines recommend that non-nuclear patterns should also be reported as a positive ANA.

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ER -

Antinuclear Antibody–Negative Systemic Lupus Erythematosus in an International Inception Cohort

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