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

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

doi:10.1002/acr.23712

Cited by 78 publications

(66 citation statements)

References 43 publications

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“…Similar results have been presented from Swedish biobanks [39]. Our finding of seroconversion of IF-ANA from positive to negative is in line with studies showing that a remaining IF-ANA positivity over time is less frequent than previously assumed [10,14,15,18]. In contrast, Ippolito et al did not report disappearance of IF-ANA over time [24].…”

Section: Discussionsupporting

confidence: 92%

Longitudinal anti-nuclear antibody (ANA) seroconversion in systemic lupus erythematosus: a prospective study of Swedish cases with recent-onset disease

Frodlund

Wetterö

Dahle

et al. 2019

Clinical &Amp; Experimental Immunology

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Summary Serum immunoglobulin (Ig)G anti‐nuclear antibodies (ANA) detected by indirect immunofluorescence (IF) microscopy remains a hallmark of systemic lupus erythematosus (SLE). Whether or not IF‐ANA status varies over time is controversial. We therefore designed a prospective study with longitudinal follow‐up of patients with recent‐onset SLE. The study population consisted of 54 recently diagnosed SLE cases, all meeting the 1982 American College of Rheumatology (ACR) and/or the 2012 Systemic Lupus International Collaborating Clinics (SLICC) criteria. Clinical follow‐up data, including disease activity, organ damage and sera, were collected from clinical onset of SLE and onwards, in most cases yearly (0‒96 months). IF‐ANA was analysed on human epithelial cells‐2 (HEp‐2) cells and categorized regarding staining patterns. Using an addressable laser bead assay (FIDIS™ Connective profile), we measured IgG‐ANA fine specificities against Ro52/SSA, Ro60/SSA, Sjögren’s syndrome type B antigen (La/SSB), Smith antigen (Sm), Smith antigen/ribonucleoprotein (Sm/RNP), U1 RNP (U1RNP), dsDNA, ribosomal‐P protein and histone. At baseline, all patients were judged ANA‐positive at an abnormal titre corresponding to the 95th percentile of healthy blood donors, but seven of 54 patients (13%) lost ANA‐positivity over time. Homogeneous (AC‐1; 46%) and speckled (AC‐4 or 5; 31%) were the most frequently observed patterns at inclusion, whereas 7% switched pattern at least once during follow‐up. Established associations between ANA fine specificities and clinical data were confirmed. Levels of anti‐Sm/RNP, but not of anti‐dsDNA, correlated with clinical disease activity [modified SLE disease activity 2000 (mSLEDAI‐2K)]. Our data indicate that a considerable proportion of Swedish patients with SLE lose ANA‐positivity over time, whereas consistent staining patterns were frequent. The clinical and mechanistic relevance of ANA seroconversion remains uncertain. Further prospective evaluations in larger SLE populations with more diverse ethnicities are warranted.

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Section: Discussionsupporting

confidence: 92%

Longitudinal anti-nuclear antibody (ANA) seroconversion in systemic lupus erythematosus: a prospective study of Swedish cases with recent-onset disease

Frodlund

Wetterö

Dahle

et al. 2019

Clinical &Amp; Experimental Immunology

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“…Importantly, we should not miss the additional information obtained by taking HEp‐2 (or HEp‐2000) cytoplasmic fluorescence into account. In this regard, we would fully concur with the argument of this study , which by its design and sample size is an important contribution to better understanding ANA performance in SLE.…”

supporting

confidence: 82%

“…In this issue, Choi et al report on a very thorough analysis of ANA in the SLE International Collaborating Clinics inception cohort that attempts to control for all these technical issues . The authors used an experienced laboratory to analyze the first available serum of 1,137 patients, where the same technician used the high‐quality gold standard method of indirect immunofluorescence to measure ANA.…”

mentioning

confidence: 99%

How Should We Consider Lupus Without Antinuclear Antibodies?

Daikh

Aringer

2019

Arthritis Care & Research

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Most patients with systemic lupus erythematosus (SLE) are ANA positive - but some are not (1). Although this is clearly a small number of patients, the size of this minor population is still debated. A fundamental question regarding this subset of patients is whether SLE can develop in the absence of an autoantibody response to nuclear antigens, with the alternative concept that ANA negativity reflects a testing anomaly. This article is protected by copyright. All rights reserved.

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“…The value of a large systemic lupus erythematosus (SLE) inception cohort cannot be overstated, but the findings of the study by Choi et al, recently published in Arthritis Care & Research , regarding the prevalence of “ANA [antinuclear antibody]–negative lupus” is debatable . The topline message from the article is that within the 1,132 patients enrolled in the group, 6.2% were anticellular antibody negative.…”

mentioning

confidence: 99%

Not positive about antinuclear antibody–negative lupus: comment on the article by Choi et al

Abeles

2020

Arthritis Care & Research

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

Cited by 78 publications

References 43 publications

Longitudinal anti-nuclear antibody (ANA) seroconversion in systemic lupus erythematosus: a prospective study of Swedish cases with recent-onset disease

Longitudinal anti-nuclear antibody (ANA) seroconversion in systemic lupus erythematosus: a prospective study of Swedish cases with recent-onset disease

How Should We Consider Lupus Without Antinuclear Antibodies?

Not positive about antinuclear antibody–negative lupus: comment on the article by Choi et al

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