Prevalence and Clinical Significance of Anti-DFS70 in Antinuclear Antibody (ANA)–positive Patients Undergoing Routine ANA Testing in a New Zealand Public Hospital

Lucas, Stacey; Chang, Wee Leong; Mérien, Fabrice

doi:10.3899/jrheum.170849

Cited by 3 publications

(4 citation statements)

References 7 publications

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“…Thus, reaching a definite consensus on their utilization as clinically reliable biomarkers for the exclusion of an SARD diagnosis will require additional multicenter trials with large, racially, ethnically and geographically diverse cohorts of different SARDs and healthy controls. These studies should use multiple highly sensitive and specific antibody detection assays, and carefully evaluate available or newly designed ANA-testing algorithms that include these antibodies [97,103,104,[128][129][130][131][132].…”

Section: Are Monospecific Anti-dfs70/ledgf Autoantibodies Clinically mentioning

confidence: 99%

Twenty years of research on the DFS70/LEDGF autoantibody-autoantigen system: many lessons learned but still many questions

Ortiz-Hernández

Sanchez-Hernández

Casiano

2020

Autoimmun Highlights

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The discovery and initial characterization 20 years ago of antinuclear autoantibodies (ANAs) presenting a dense fine speckled (DFS) nuclear pattern with strong staining of mitotic chromosomes, detected by indirect immunofluorescence assay in HEp-2 cells (HEp-2 IIFA test), has transformed our view on ANAs. Traditionally, ANAs have been considered as reporters of abnormal immunological events associated with the onset and progression of systemic autoimmune rheumatic diseases (SARD), also called ANA-associated rheumatic diseases (AARD), as well as clinical biomarkers for the differential diagnosis of these diseases. However, based on our current knowledge, it is not apparent that autoantibodies presenting the DFS IIF pattern fall into these categories. These antibodies invariably target a chromatin-associated protein designated as dense fine speckled protein of 70 kD (DFS70), also known as lens epitheliumderived growth factor protein of 75 kD (LEDGF/p75) and PC4 and SFRS1 Interacting protein 1 (PSIP1). This multi-functional protein, hereafter referred to as DFS70/LEDGF, plays important roles in the formation of transcription complexes in active chromatin, transcriptional activation of specific genes, regulation of mRNA splicing, DNA repair, and cellular survival against stress. Due to its multiple functions, it has emerged as a key protein contributing to several human pathologies, including acquired immunodeficiency syndrome (AIDS), leukemia, cancer, ocular diseases, and Rett syndrome. Unlike other ANAs, "monospecific" anti-DFS70/LEDGF autoantibodies (only detectable ANA in serum) are not associated with SARD and have been detected in healthy individuals and some patients with non-SARD inflammatory conditions. These observations have led to the hypotheses that these antibodies could be considered as negative biomarkers of SARD and might even play a protective or beneficial role. In spite of 20 years of research on this autoantibody-autoantigen system, its biological and clinical significance still remains enigmatic. Here we review the current state of knowledge of this system, focusing on the lessons learned and posing emerging questions that await further scrutiny as we continue our quest to unravel its significance and potential clinical and therapeutic utility.

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Section: Are Monospecific Anti-dfs70/ledgf Autoantibodies Clinically mentioning

confidence: 99%

Twenty years of research on the DFS70/LEDGF autoantibody-autoantigen system: many lessons learned but still many questions

Ortiz-Hernández

Sanchez-Hernández

Casiano

2020

Autoimmun Highlights

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“…In the patient selection domains, one study was assessed as having a high risk of bias and concerns of applicability because it only enrolled patients with available results of ANA and anti-ENA [ 31 ]. One study was assessed as having an unclear risk due to inadequate information [ 32 ]. For the index test, one study was assessed as having an unclear risk of bias and concerns of applicability because the index test threshold was not reported [ 33 ].…”

Section: Resultsmentioning

confidence: 99%

“…For the reference standard, only one of the studies applied the classification criteria of SARD [2]. Due to possible heterogeneity in the clinical diagnosis and practice, the studies using reference standards other than classification criteria were assessed as having an unclear risk of bias and applicability in the reference standard [30][31][32][33][34][35][36]. For flow and timing, because none of the enrolled studies specified the time interval between the index test and the diagnosis of SARD, the appropriateness of the interval between the index test (anti-DFS70 antibodies) and the reference standard (the diagnosis of SARD) could not be assessed.…”

Section: Quality Assessmentmentioning

confidence: 99%

Anti-DFS70 Antibodies for Differentiating Systemic Autoimmune Rheumatic Disease in Patients with Positive ANA Tests: A Systematic Review and Meta-Analysis

et al. 2021

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Anti-DFS70 antibodies have been proposed as a marker to exclude systemic autoimmune rheumatic disease (SARD). We conducted this systematic diagnostic test accuracy review and meta-analysis to determine the performance of anti-DFS70 antibodies in patients with a positive anti-nuclear antibody (ANA) test result to exclude SARD. We searched PubMed, Embase, Web of Science, Scopus and the Cochrane Library up to 22 February 2021, and included studies examining the diagnostic accuracy of anti-DFS70 antibodies in patients with a positive ANA test result. The results were pooled using a hierarchical bivariate model and plotted in summary receiver operating characteristic curves. R software and Stata Statistical Software were used for the statistical analysis. Eight studies with 4168 patients were included. The summary sensitivity was 0.19 (95% confidence interval: 0.12–0.28) and the specificity was 0.93 (95% confidence interval: 0.88–0.96). The area under the curve was 0.69 (95% confidence interval: 0.64–0.72). The meta-regression analysis showed that targeting only ANA-associated rheumatic disease was associated with higher specificity. In addition, the studies with a non-SARD prevalence of <80% and using a chemiluminescence assay were associated with higher specificity. Anti-DFS70 antibodies have high specificity for the exclusion of SARD among patients presenting with a positive ANA test, but the sensitivity is low.

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“…Due to the low prevalence of monospecific anti-DFS70 in adult patients with AARD, several authors have suggested including tests for anti-DFS70 antibodies in the diagnostic approach for suspected AARD ( 24 , 25 , 35 , 49 – 55 ). A recent systematic review and meta-analysis showed a high specificity for anti-DFS70 antibodies to exclude AARD among patients with a positive ANA-IIF ( 56 ).…”

Section: Discussionmentioning

confidence: 99%

Low Prevalence of Anti-DFS70 Antibodies in Children With ANA-Associated Autoimmune Disease

et al. 2022

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IntroductionAnti-DFS70 antibodies occur in healthy individuals with various medical conditions. Unlike other anti-nuclear autoantibodies (ANA), they are not associated with systemic autoimmune disease in adult patients. To date, only a few studies have addressed the prevalence and/or clinical relevance of anti-DFS70 autoantibodies in children with and without autoimmune disease.MethodsIncluded in this retrospective cross-sectional mono-centric study were 308 pediatric patients with suspected or known autoimmune conditions who had a positive ANA in indirect immune fluorescence (IIF) screening and who were screened for anti-DFS70 antibodies by extractable nuclear antigen antibodies (ENA) immunoblot. Patients were assigned to four different diagnostic categories according to their diagnosis in the corresponding medical record: (a) absence of autoimmune or rheumatic disease (noARD, n = 116); (b) suspected autoimmunity without definitive diagnosis (sAI, n = 48); (c) other rheumatic disease (ORD) (n = 115); and (d) ANA-associated autoimmune disease (AARD, n = 29).ResultsThe prevalence of anti-DFS70 antibodies in the overall cohort was 33.8%. Among children without ARD (46.6%, 54/116), prevalence was significantly higher than among children with ORD (23.7%, 27/115, p = 0.0003) or AARD (17.2%, 5/29, p = 0.0054). Among all of the anti-DFS70 positive patients with AARD, other autoantibodies were found in the ENA immunoblot. In contrast, among anti-DFS70 positive patients with ORD (11.5%, 4/27), sAI (33.3%, 6/18) and noARD (16.7%, 9/54), other autoantibodies infrequently were detected (p = 0.0005). Patients with uveitis rarely were positive for anti-DFS70 antibodies (7.7%, 1/13). No association was found between anti-DFS70 antibodies and a history of allergic conditions (p = 0.51). The concordance between a typical DFS pattern in IIF and the detection of anti-DFS70 antibodies by immunoblot was 59.3%.ConclusionAs with adults, the higher prevalence of anti-DFS70 among children without autoimmune disease confirms the mutual exclusion for this autoantibody in the pathogenesis of ARD. Among ANA-positive children, monospecific anti-DFS70 antibodies may help to discriminate between AARD and not-AARD-related conditions.

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Prevalence and Clinical Significance of Anti-DFS70 in Antinuclear Antibody (ANA)–positive Patients Undergoing Routine ANA Testing in a New Zealand Public Hospital

Cited by 3 publications

References 7 publications

Twenty years of research on the DFS70/LEDGF autoantibody-autoantigen system: many lessons learned but still many questions

Twenty years of research on the DFS70/LEDGF autoantibody-autoantigen system: many lessons learned but still many questions

Anti-DFS70 Antibodies for Differentiating Systemic Autoimmune Rheumatic Disease in Patients with Positive ANA Tests: A Systematic Review and Meta-Analysis

Low Prevalence of Anti-DFS70 Antibodies in Children With ANA-Associated Autoimmune Disease

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