Development, Sensibility, and Validity of a Systemic Autoimmune Rheumatic Disease Case Ascertainment Tool

Armstrong, Susan; Wither, Joan E.; Borowoy, Alan M.; Landolt-Marticorena, Carolina; Davis, Aileen M.

doi:10.3899/jrheum.160327

Cited by 7 publications

(5 citation statements)

References 23 publications

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“…Sex-matched healthy controls (HC) were recruited from hospital/laboratory personnel and were ANA and specific anti-nuclear antibody negative. Information on family history of SARD or rheumatoid arthritis was ascertained using a validated questionnaire [ 26 ]. The study was approved by the Research Ethics Boards of both recruiting hospitals and all participants gave signed informed consent.…”

Section: Methodsmentioning

confidence: 99%

The presence of anti-nuclear antibodies alone is associated with changes in B cell activation and T follicular helper cells similar to those in systemic autoimmune rheumatic disease

et al. 2018

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BackgroundDiagnosis of systemic autoimmune rheumatic diseases (SARD) relies on the presence of hallmark anti-nuclear antibodies (ANA), many of which can be detected years before clinical manifestations. However, ANAs are also seen in healthy individuals, most of whom will not develop SARD. Here, we examined a unique cohort of asymptomatic ANA+ individuals to determine whether they share any of the cellular immunologic features seen in SARD.MethodsHealthy ANA− controls and ANA+ (ANA ≥1:160 by immunofluorescence) participants with no SARD criteria, with at least one criterion (undifferentiated connective tissue disease (UCTD)), or meeting SARD classification criteria were recruited. Peripheral blood cellular immunological changes were assessed by flow cytometry and transcript levels of BAFF, interferon (IFN)-induced and plasma cell-expressed genes were quantified by NanoString.ResultsA number of the immunologic abnormalities seen in SARD, including changes in peripheral B (switched memory) and T (iNKT, T regulatory, activated memory T follicular helper) subsets and B cell activation, were also seen in asymptomatic ANA+ subjects and those with UCTD. The extent of these immunologic changes correlated with ANA titer or the number of different specific ANAs produced. Principal component analysis of the cellular data indicated that a significant proportion of asymptomatic ANA+ subjects and subjects with UCTD clustered with patients with early SARD, rather than ANA− healthy controls.ConclusionsANA production is associated with altered T and B cell activation even in asymptomatic individuals. Some of the currently accepted cellular features of SARD may be associated with ANA production rather than the immunologic events that cause symptoms in SARD.Electronic supplementary materialThe online version of this article (10.1186/s13075-018-1752-3) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

The presence of anti-nuclear antibodies alone is associated with changes in B cell activation and T follicular helper cells similar to those in systemic autoimmune rheumatic disease

et al. 2018

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“…(2, 25) We identified subjects with SARDs, defined by having at least one Read code for one of the included conditions: SLE, SSc, Sjogren’s syndrome, dermatomyositis, polymyositis, mixed connective tissue disease, ANCA-associated vasculitis, or Behcet’s disease. (2, 25) We did not include individuals with diagnoses of giant cell arteritis or polymyalgia rheumatica to improve comparability within the SARD cohort, as those conditions exclusively affect an older age group. (26) Read code diagnoses have been previously validated in a similar UK database, and diagnoses of connective tissue diseases were found to be 80% accurate.…”

Section: Methodsmentioning

confidence: 99%

The Effect of Statin Use on Mortality in Systemic Autoimmune Rheumatic Diseases

Jorge

Lu²,

Keller³

et al. 2018

J Rheumatol

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“…From July 2013 to October 2018, individuals referred for a rheumatology assessment because of a recently discovered positive ANA test were serially recruited at the Toronto Western and Mount Sinai Hospitals. At the first visit the subjects underwent an extensive history and physical exam seeking symptoms or signs of SARD, with all demographic and clinical data being recorded on a standardized form [9]. Individuals with an ANA !1:160 were stratified into three groups: ANA þ NS individuals lacking SARD criteria as defined by the 1997 ACR criteria for SLE [10], 2013 ACR-EULAR criteria for SSc [11] or 2016 ACR-EULAR criteria for SS [12]; UCTD patients with one or more SARD criteria but with insufficient criteria for a diagnosis; or early (within 2 years of diagnosis) untreated (except antimalarials) SARD patients.…”

Section: Subjects and Data Collectionmentioning

confidence: 99%

Serological abnormalities that predict progression to systemic autoimmune rheumatic diseases in antinuclear antibody–positive individuals

et al. 2021

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Objective We investigated the auto-antibody (auto-Ab) profiles in anti-nuclear antibody-positive (ANA+) individuals lacking Systemic Autoimmune Rheumatic Disease (SARD) and early SARD patients, to determine the key differences between these groups and identify factors that are associated with an increased risk of symptomatic progression within the next two years in ANA+ individuals. Methods Using custom antigen (Ag) microarrays, 144 IgM and IgG auto-Abs were surveyed in 84 asymptomatic and 123 symptomatic (48 undifferentiated connective tissue disease (UCTD) and 75 SARD patients) ANA+ individuals. Auto-Ab were compared in ANA+ individuals lacking a SARD diagnosis with ≥ 2 years follow-up (n = 52), including all those who demonstrated progression (n = 14) during this period, with changes over time assessed in a representative subset. Results We show that ANA+ individuals have auto-Ab to many self-Ag that are not being captured by current screening techniques and very high levels of these auto-Abs are predominantly restricted to early SARD patients, with SLE patients displaying reactivity to many more auto-Ags than the other groups. In general, the symptoms that developed in progressors mirrored those seen in SARD patients with similar patterns of auto-Ab. Only anti-Ro52 Abs were found to predict progression (positive predictive value 46%, negative predictive value 89%). Surprisingly, over 2 years follow-up the levels of auto-Ab remained remarkably stable regardless of whether individuals progressed or not. Conclusion Our findings strongly argue that development of assays with an expanded set of auto-Ags and enhanced dynamic range would improve the diagnostic and prognostic ability of auto-Ab testing.

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Development, Sensibility, and Validity of a Systemic Autoimmune Rheumatic Disease Case Ascertainment Tool

Abstract: This SARD case ascertainment tool has demonstrable sensibility and validity. The use of both screening and confirmatory questions confers added accuracy.

Cited by 7 publications

References 23 publications

The presence of anti-nuclear antibodies alone is associated with changes in B cell activation and T follicular helper cells similar to those in systemic autoimmune rheumatic disease

The presence of anti-nuclear antibodies alone is associated with changes in B cell activation and T follicular helper cells similar to those in systemic autoimmune rheumatic disease

The Effect of Statin Use on Mortality in Systemic Autoimmune Rheumatic Diseases

Serological abnormalities that predict progression to systemic autoimmune rheumatic diseases in antinuclear antibody–positive individuals

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