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

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Choi MY1, Clarke AE1, St Pierre Y2, Hanly JG3, Urowitz MB4, Romero-Diaz J5, Gordon C6, Bae SC7, Bernatsky S8, Wallace DJ9, Merrill JT10, Isenberg DA11, Rahman A11, Ginzler EM12, Petri M13, Bruce IN14, Dooley MA15, Fortin PR16, Gladman DD4, Sanchez-Guerrero J17, Steinsson K18, Ramsey-Goldman R19, Khamashta MA20, Aranow C21, Alarcón GS22, Manzi S23, Nived O24, Zoma AA25, van Vollenhoven RF26, Ramos-Casals M27, Ruiz-Irastorza G28, Lim SS29, Kalunian KC30, Inanc M31, Kamen DL32, Peschken CA33, Jacobsen S34, Askanase A35, Stoll T36, Buyon J37, Mahler M38, Fritzler MJ1. Arthritis Care Res (Hoboken). 2018 Jul 25. doi: 10.1002/acr.23712. [Epub ahead of print]

Abstract

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Abstract

OBJECTIVES: The spectrum of antinuclear antibodies (ANA) is changing to include both nuclear staining as well as cytoplasmic and mitotic cell patterns (CMPs) and accordingly a change in terminology to anti-cellular antibodies. This study examined the prevalence of indirect immunofluorescence (IIF) anti-cellular antibody staining using the Systemic Lupus International Collaborating Clinics inception cohort.

METHODS: Anti-cellular antibodies were detected by IIF on HEp-2000 substrate utilizing the baseline serum. Three serological subsets were examined: 1) ANA-positive (presence of either nuclear or mixed nuclear/CMP staining), 2) anti-cellular antibody-negative (absence of any intracellular staining), and 3) isolated CMP staining. The odds of being anti-cellular antibody-negative versus ANA or isolated CMP-positive was assessed by multivariable analysis.

RESULTS: 1137 patients were included; 1049/1137 (92.3%) were ANA-positive, 71/1137 (6.2%) were anti-cellular antibody-negative, and 17/1137 (1.5%) had isolated CMP. The isolated CMP group did not differ from the ANA-positive or anti-cellular antibody-negative group in clinical, demographic or serologic features. Patients who were older (OR 1.02 [95% CI: 1.00, 1.04]), of Caucasian race/ethnicity (OR 3.53 [95% CI: 1.77, 7.03]), or on high dose glucocorticoids at or prior to enrolment (OR 2.39 [95% CI: 1.39, 4.12]) were more likely to be anti-cellular antibody-negative. Patients on immunosuppressants (OR 0.35 [95% CI: 0.19, 0.64]) or with anti-SSA/Ro60 (OR 0.41 [95% CI: 0.23, 0.74]) or anti-UI-RNP (OR 0.43 [95% CI: 0.20, 0.93]) were less likely to be anti-cellular antibody-negative.

CONCLUSIONS: In newly diagnosed SLE, 6.2% of patients were anti-cellular antibody-negative and 1.5% had isolated CMP. The prevalence of anti-cellular antibody-negative SLE will likely decrease as emerging nomenclature guidelines recommend that non-nuclear patterns should also be reported as a positive ANA.