DFS70 antibodies – biomarkers for the exclusion of ANA-associated autoimmune rheumatic diseases

2015 ◽  
Vol 38 (6) ◽  
Author(s):  
Karsten Conrad ◽  
Nadja Röber ◽  
Sebastian Rudolph ◽  
Michael Mahler
Keyword(s):  
Rheumatic Diseases ◽  
Antinuclear Antibodies ◽  
Laboratory Diagnosis ◽  
Healthy Individuals ◽  
Autoimmune Rheumatic Diseases ◽  
Novel Biomarkers ◽  
Specific Autoantibody ◽  
Well Differentiated ◽  
Dsdna Antibodies ◽  
Posttest Probability

AbstractDespite the progress in the establishment of specific autoantibody assays, screening for antinuclear antibodies (ANA) by indirect immunofluorescence on HEp-2 cells for quality-oriented laboratory diagnosis of ANA associated rheumatic diseases (AARD) remains indispensable. Research results on the relevance of the dense fine speckled (DFS) pattern and DFS70 antibodies disclosed novel possibilities to optimize the serological stepwise diagnostics of AARD. The DFS pattern on HEp-2 cells is well differentiated from the classic “homogeneous” ANA pattern associated with dsDNA antibodies. In DFS pattern positive sera the most important detectable ANA specificity is the DFS70 antibody (synonym LEDGF antibody). This antibody is also the most frequent ANA specificity in ANA positive healthy persons. The prevalence of DFS70 antibodies in AARD patients is significantly lower compared with the prevalence in ANA-positive healthy individuals. There is a negative association between DFS70 antibodies and AARD, especially if no concomitant AARD-specific autoantibodies are found. Isolated DFS70 antibodies are detectable in <1% of AARD, but are detectable in 5%–11% of healthy individuals. In the presence of an isolated DFS70 antibody, the posttest probability for AARD is reduced significantly. DFS70 antibodies are valuable novel biomarkers for the improved interpretation of positive ANA but without detectable AARD associated autoantibodies and should be integrated in modified test algorithms to avoid unnecessary referrals and examinations of ANA-positive subjects.

Anti-DFS70/LEDGF Antibodies Are More Prevalent in Healthy Individuals Compared to Patients with Systemic Autoimmune Rheumatic Diseases

2012 ◽  
Vol 39 (11) ◽  
pp. 2104-2110 ◽  
Author(s):  
MICHAEL MAHLER ◽  
TODD PARKER ◽  
CAROL L. PEEBLES ◽  
LUIS E. ANDRADE ◽  
ANDREAS SWART ◽  
...  
Keyword(s):  
Rheumatic Diseases ◽  
Lupus Erythematosus ◽  
Antinuclear Antibodies ◽  
Graves Disease ◽  
Healthy Individuals ◽  
Systemic Lupus ◽  
Diagnostic Significance ◽  
Autoimmune Rheumatic Diseases ◽  
Sequential Samples ◽  
Clinical Associations

Objective.Antinuclear antibodies (ANA) are a serological hallmark of systemic autoimmune rheumatic diseases (SARD) such as systemic lupus erythematosus (SLE). While a number of ANA patterns detected by indirect immunofluorescence (IIF) have diagnostic significance, autoantibodies producing the dense fine speckled (DFS) pattern have been reported to be more prevalent in healthy individuals than in SARD.Methods.Sequential samples submitted for ANA testing were screened for anti-DFS antibodies by IIF (n = 3263). Samples with the DFS pattern were tested for anti-DFS70/lens epithelium–derived growth factor (LEDGF) antibodies by ELISA and by a novel chemiluminescence assay (CIA, Quanta Flash DFS70). Sera from patients with various diseases and healthy individuals were tested for anti-DFS70/LEDGF antibodies by CIA. A cohort of 251 patients with SLE was used to analyze serological and clinical associations of anti-DFS70 antibodies.Results.The frequency of anti-DFS antibodies by IIF was 1.62%. The prevalence of anti-DFS70/LEDGF antibodies as detected by CIA in the different cohorts was 8.9% in healthy individuals, 2.8% in SLE, 2.6% in rheumatoid arthritis, 4.0% in asthma, 5.0% in interstitial cystitis, 1.7% in Graves’ disease, and 6.0% in Hashimoto’s thyroiditis. Of note, the prevalence of anti-DFS70/LEDGF antibodies was significantly higher in healthy individuals compared to patients with SARD (p = 0.00085). In SLE results, anti-DFS70/LEDGF antibodies were not significantly associated with clinical features or other autoantibodies typically found in SLE. Only 1/7 SLE sera showed anti-DFS70/LEDGF, but no other autoantibody reactivity.Conclusion.“Monospecific” anti-DFS70/LEDGF antibodies may represent a biomarker for differentiating SARD from non-SARD individuals, but there is a need for a reliable assay to ensure reactivity to DFS70.

scholarly journals Prevalence of anti-dense fine speckled 70 antibodies in healthy individuals and patients with antinuclear antibody-associated autoimmune rheumatic diseases in Japan

Medicine ◽  
2021 ◽  
Vol 100 (9) ◽  
pp. e24556
Author(s):  
Nobuhide Hayashi ◽  
Kenichi Uto ◽  
Akiko Imanishi ◽  
Daisuke Sugiyama ◽  
Akio Morinobu ◽  
...  
Keyword(s):  
Rheumatic Diseases ◽  
Antinuclear Antibody ◽  
Healthy Individuals ◽  
Autoimmune Rheumatic Diseases

scholarly journals Increased frequency of antinuclear antibodies in elderly subjects: fact or artifact?

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Maria Cristina Sacchi ◽  
Aldo Bellora ◽  
Stefania Tamiazzo
Keyword(s):  
Elderly Patients ◽  
Rheumatic Diseases ◽  
Gold Standard ◽  
Antinuclear Antibodies ◽  
The Elderly ◽  
Diagnostic Methods ◽  
Elderly Subjects ◽  
Title 1 ◽  
Autoimmune Rheumatic Diseases ◽  
Real Increase

Objectives: To evaluate the frequency of antinuclear antibodies (ANA) positive in elderly patients. Methodology: Ana test was evaluate in 1000 eldery patients with Indirect Immunofluorescence (IFI), which still represents the gold standard for the research of this type of autoantibodies. Results: We enrolled 1000 elderly patients ≥ 75 years (75-97y) from September 2019 to April 2020. In 29% of patients we found a positive ANA with a title ≥ 1:160. Conclusions: Our results confirm the data present in the literature. The reasons because in these patients there is an increase in the positivity of ANA are not yet known. Therefore, are these results the expression of a real increase in autoimmune rheumatic diseases in the elderly (predictive antibodies) due to the presence of other concomitant pathologies and the intake of drugs or may they depend on the greater sensitivity of the latest generation diagnostic methods? More comprehensive studies are needed to better understand this phenomenon.

scholarly journals The importance of detecting anti-DFS70 in routine clinical practice: comparison of different care settings

2018 ◽  
Vol 56 (7) ◽  
pp. 1090-1099 ◽  
Author(s):  
Carolien Bonroy ◽  
Sofie Schouwers ◽  
Mario Berth ◽  
Muriel Stubbe ◽  
Yves Piette ◽  
...  
Keyword(s):  
Antinuclear Antibodies ◽  
Care Setting ◽  
Clinical Symptoms ◽  
Solid Phase ◽  
Tertiary Care ◽  
Clinical Importance ◽  
Clinical Information ◽  
Routine Clinical Practice ◽  
Healthy Individuals ◽  
Autoimmune Rheumatic Diseases

AbstractBackground:Screening for antinuclear antibodies by indirect immunofluorescence (ANA-IIF) is essential in the diagnostic workup of ANA-associated autoimmune rheumatic diseases (AARDs). However, also healthy individuals may test positive, making the interpretation challenging. Recent reports suggest that dense fine speckled 70 antibodies (anti-DFS70) may facilitate this challenge. Here, we investigate their clinical importance based on data from four Belgian laboratories (one primary, two secondary and one tertiary care).Methods:At least one specific DFS70 assay (DFS70 IgG ELISA or lineblot [Euroimmun, full length antigen] and/or DFS70 IgG CLIA [Inova Diagnostics, truncated antigen]) was performed on four consecutive cohorts of homogeneous-like ANA-IIF samples (n=697). Co-occurrence with AARD-specific ANA and clinical information were documented in the anti-DFS70-positive samples.Results:Using a combination of solid phase techniques, we found between 7.6% and 26% anti-DFS70 in the different cohorts. Focusing on anti-DFS70 CLIA-positive samples without co-occurrence of AARD-specific ANA, we observed a trend towards lower frequency in tertiary (8% [p=0.0786]) and secondary care (12% [p=0.1275] and 6% [p<0.001]) compared to primary care (21%). Moreover, in this specific subpopulation, AARD was less frequent (0%–50% compared to 6%–77% in the total anti-DFS70-positive group).Conclusions:Anti-DFS70 prevalence depends on the applied assay and care setting. Our data suggest that, for an ANA-IIF-positive patient, it is rather the absence of AARD-associated ANA and clinical symptoms that contribute to the exclusion of AARD than the presence of anti-DFS70. Nevertheless, isolated anti-DFS70 helps to clarify positive ANA-IIF results, especially if pretest probability for AARD is low.

Diagnostic value of monospecifc DFS70 antibodies in systemic utoimmune rheumatic diseases

2021 ◽  
pp. 38-41
Author(s):  
E. N. Aleksandrova ◽  
A. A. Novikov ◽  
N. G. Klyukvina ◽  
V. I. Vasiliev ◽  
G. V. Lukina
Keyword(s):  
Rheumatic Diseases ◽  
Lupus Erythematosus ◽  
Antinuclear Antibodies ◽  
Clinical Signs ◽  
Predictive Marker ◽  
Diagnostic Value ◽  
Genetically Engineered ◽  
Nuclear Antigen ◽  
Healthy Individuals ◽  
Healthy Donors

The detection in serum of monospecifc antibodies that induce a dense fne-speckled fluorescence when interacting with the DFS70 / LEDGF / p75 nuclear antigen is negatively associated with the development of systemic autoimmune rheumatic diseases (SARD) and increases the diagnostic specifcity of the screening study of antinuclear antibodies (ANA) using indirect immunofluorescence on HEp-2 cells (IIF-HEp-2). The results of assessing the clinical signifcance of anti-DFS70 antibodies vary depending on the test systems and the selection of patient groups. The aim of this work is to study the frequency of detection of monospecifc anti-DFS70 antibodies in blood serum in healthy individuals and patients with SARD. Sera of 74 healthy donors and 59 patients with SARD were studied (27 – systemic lupus erythematosus – SLE, 15 – Sjogren's syndrome – SjS, 17 – rheumatoid arthritis – RA). Classical antinuclear antibodies (ANA) and anti-DFS70 antibodies were determined by IIF using a mixture of standard and genetically engineered DFS70-KO HEp-2 cells that do not express DFS70 / LEDGF / p75 as a substrate. 14.9% of healthy donors and 83.1% of SARD patients (96.3% – SLE, 100.0% – SS, 47.1% – RA) were seropositive for antinuclear factor (ANF). Classical ANA with homogeneous, speckled, nucleolar, cytoplasmic, mixed types of fluorescence and the absence of anti-DFS70 antibodies were found in all ANF-positive patients with SARD and in 8.1% of healthy donors. Monospecifc anti-DFS70 antibodies without classical ANA were detected in 6.8% of healthy individuals and were absent in SARS. Among ANF-positive healthy donors, the frequency of isolated detection of anti-DFS70 antibodies was 45.5%. The detection of monospecifc anti-DFS70 antibodies can be considered as a potential predictive marker for excluding the diagnosis of SARD in ANF-positive patients with no or unclear clinical signs of these diseases.

scholarly journals Factors Associated With the Antinuclear Antibody Titer of Patients With Systemic Autoimmune Rheumatic Diseases After Treatment: A Retrospective Study

2021 ◽  
Author(s):  
Yun Xiao ◽  
Yan Zhang ◽  
Yiqiang Lin ◽  
Jiajia Wang ◽  
Yanli Zeng
Keyword(s):  
Retrospective Study ◽  
Rheumatic Diseases ◽  
Antinuclear Antibodies ◽  
Multivariate Analyses ◽  
Demographic Data ◽  
Post Treatment ◽  
Clinical Database ◽  
Factors Associated ◽  
Medical College ◽  
Autoimmune Rheumatic Diseases

Abstract Background: Antinuclear antibodies (ANAs) are a serological hallmark of systemic autoimmune rheumatic diseases (SARDs); however, few studies have investigated their post-treatment levels.Objective: The mechanism by which ANA titers are upregulated in SARDs remains unclear. We assessed factors associated with the ANA titer after treatment.Methods: In this retrospective study we analyzed the clinical database of Zhongshan Hospital, Medical College of Xiamen. Demographic data and baseline and 12-month post-treatment ANA titers were collected. Bivariate and multivariate analyses were performed to determine the factors associated with the ANA titer.Results: This study identified 31,923 patients who underwent ANA assay for SARDs screening, and a total of 1043 patients were included in the study. Approximately 16% of the patients showed a decrease in the serological ANA titer. Men were twice as likely to achieve a decrease in the serum ANA titer than women (P = 0.055), and younger patients (<20) were 3× more likely to experience such a decrease (P = 0.005) compared to older patients (≥60 years). A baseline ANA titer >1:10000 was associated with a significantly lower (47×) serum ANA titer compared with the baseline ANA titer at a dilution of 1:100 (P < 0.001).. Homogeneous (P = 0.095) and cytoplasmic speckled (P = 0.158) had over threefold greater decrease in the serum ANA titer compared with other patterns.Conclusion: We found that a decrease in the serum ANA titer at 12 months after treatment for SARDs is associated with age, sex, ANA baseline titers, and ANA pattern.

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