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 & 22 others 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

Research output: Contribution to journalArticleAcademicpeer-review

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 languageEnglish
Pages (from-to)893-902
JournalArthritis Care and Research
Volume71
Issue number7
DOIs
Publication statusPublished - 1 Jul 2019

Cite this

Choi, M. Y., Clarke, A. E., St. Pierre, Y., Hanly, J. G., Urowitz, M. B., Romero-Diaz, J., ... 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
Choi, May Y. ; Clarke, Ann E. ; St. Pierre, Yvan ; Hanly, John G. ; Urowitz, Murray B. ; Romero-Diaz, Juanita ; Gordon, Caroline ; Bae, Sang-Cheol ; Bernatsky, Sasha ; Wallace, Daniel J. ; Merrill, Joan T. ; Isenberg, David A. ; Rahman, Anisur ; Ginzler, Ellen M. ; Petri, Michelle ; Bruce, Ian N. ; Dooley, Mary A. ; Fortin, Paul R. ; Gladman, Dafna D. ; Sanchez-Guerrero, Jorge ; Steinsson, Kristjan ; Ramsey-Goldman, Rosalind ; Khamashta, Munther A. ; Aranow, Cynthia ; Alarcón, Graciela S. ; Manzi, Susan ; Nived, Ola ; Zoma, Asad A. ; van Vollenhoven, Ronald F. ; Ramos-Casals, Manuel ; Ruiz-Irastorza, Guillermo ; Lim, S. Sam ; Kalunian, Kenneth C. ; Inanc, Murat ; Kamen, Diane L. ; Peschken, Christine A. ; Jacobsen, Soren ; Askanase, Anca ; Stoll, Thomas ; Buyon, Jill ; Mahler, Michael ; Fritzler, Marvin J. / Antinuclear Antibody–Negative Systemic Lupus Erythematosus in an International Inception Cohort. In: Arthritis Care and Research. 2019 ; Vol. 71, No. 7. pp. 893-902.
@article{27e1c69f7c61436c9c32c7dd5c8c493a,
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 Sang-Cheol Bae 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.}",
year = "2019",
month = "7",
day = "1",
doi = "10.1002/acr.23712",
language = "English",
volume = "71",
pages = "893--902",
journal = "Arthritis Care & Research",
issn = "2151-464X",
publisher = "John Wiley and Sons Inc.",
number = "7",

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Choi, MY, Clarke, AE, St. Pierre, Y, Hanly, JG, Urowitz, MB, Romero-Diaz, J, Gordon, C, Bae, S-C, 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

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

In: Arthritis Care and Research, Vol. 71, No. 7, 01.07.2019, p. 893-902.

Research output: Contribution to journalArticleAcademicpeer-review

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 - 2019/7/1

Y1 - 2019/7/1

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.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85057395115&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/30044551

U2 - 10.1002/acr.23712

DO - 10.1002/acr.23712

M3 - Article

VL - 71

SP - 893

EP - 902

JO - Arthritis Care & Research

JF - Arthritis Care & Research

SN - 2151-464X

IS - 7

ER -

Choi MY, Clarke AE, St. Pierre Y, Hanly JG, Urowitz MB, Romero-Diaz J et al. Antinuclear Antibody–Negative Systemic Lupus Erythematosus in an International Inception Cohort. Arthritis Care and Research. 2019 Jul 1;71(7):893-902. https://doi.org/10.1002/acr.23712