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.

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 Detection of Antinuclear Antibodies by Use of an Enzyme Immunoassay with Nuclear HEp-2 Cell Extract and Recombinant Antigens: Comparison with Immunofluorescence Assay in 307 Patients

2001 ◽  
Vol 47 (9) ◽  
pp. 1649-1659 ◽  
Author(s):  
Nobuhide Hayashi ◽  
Tomoko Kawamoto ◽  
Masahiko Mukai ◽  
Akio Morinobu ◽  
Masahiro Koshiba ◽  
...  
Keyword(s):  
Connective Tissue ◽  
Enzyme Immunoassay ◽  
Sensitivity And Specificity ◽  
Lupus Erythematosus ◽  
Antinuclear Antibodies ◽  
Connective Tissue Diseases ◽  
Cell Extract ◽  
Healthy Individuals ◽  
Cell Extracts ◽  
Disease Specific

Abstract Background: A new enzyme immunoassay (EIA) for automated detection of antinuclear antibodies (ANAs) uses a mixture of HEp-2 cell extracts and multiple recombinant nuclear antigens immobilized on beads. We compared this EIA and an immunofluorescence (IF) assay in a large group of patients and controls. Methods: We studied 492 healthy individuals and 307 patients with connective tissue diseases (CTDs). Sera were tested by an automated EIA (COBAS® Core HEp2 ANA EIA; Roche Diagnostics) and IF. Samples were also tested for eight disease-specific antibodies, including antibodies against U1RNP, Sm, SSA/Ro, SSB/La, Scl-70, Jo-1, dsDNA, and centromere. Results: Areas under ROC curves for the EIA were greater than (P = 0.008–0.012) or numerically identical to areas for the IF method for each of six CTDs studied. ROC areas for EIA were 0.98 (95% confidence interval, 0.95–0.99), 0.99 (0.96–1.00), and 0.99 (0.98–1.00) in systemic lupus erythematosus (n = 111), systemic sclerosis (n = 39), and mixed connective tissue disease (n = 33), respectively. For all 258 CTD patients with conditions other than rheumatoid arthritis (RA), the sensitivity and specificity of the IF method at a cutoff dilution of 1:40 were 92% and 65%, respectively, vs 93% and 79% for the EIA at a cutoff of 0.6. For the IF method at a cutoff dilution of 1:160, sensitivity and specificity were 81% and 87%, respectively, vs 84% and 94%, respectively, for the EIA at a cutoff of 0.9. For 207 sera containing at least one of eight disease-specific ANAs, positivities for the EIA and the IF method were 97.1% and 97.6%, respectively, at cutoffs of 0.6 and 1:40 (P = 0.76). Conclusions: An EIA that can be performed by a fully automated instrument distinguishes CTDs (except RA) from healthy individuals with both higher sensitivity and specificity than the IF method when the cutoff index was set at 0.9. Moreover, it can be used to exclude the presence of disease-specific ANAs by setting the cutoff index at 0.6 with almost the same efficacy as the IF method.

scholarly journals High Prevalence of Antinuclear Antibodies in Children with Thyroid Autoimmunity

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Maria Segni ◽  
Ida Pucarelli ◽  
Simona Truglia ◽  
Ilaria Turriziani ◽  
Chiara Serafinelli ◽  
...  
Keyword(s):  
Autoimmune Diseases ◽  
Rheumatic Diseases ◽  
Antinuclear Antibodies ◽  
Pediatric Patients ◽  
Thyroid Autoimmunity ◽  
Disease Onset ◽  
Nuclear Antigen ◽  
Chronic Lymphocytic Thyroiditis ◽  
Autoimmune Thyroid Diseases ◽  
Autoimmune Thyroid

Background. Antinuclear antibodies (ANA) are a hallmark of many autoimmune diseases and can be detected many years before disease onset. Autoimmune thyroid diseases (AITD) are frequently associated with other organ- and non-organ-specific autoimmune disorders.Objectives. To assess the prevalence of ANA in pediatric patients with AITD and their clinical correlations.Methods. Ninety-three consecutive pediatric patients with AITD were enrolled (86 children with chronic lymphocytic thyroiditis and 7 with Graves’ disease). ANA, anti-double DNA (anti-dsDNA) antibodies, anti-extractable nuclear antigen (anti-ENA), anti-cyclic citrullinated peptide antibodies (anti-CCP), and rheumatoid factor (RF) was obtained. Signs and symptoms potentially related to rheumatic diseases in children were investigated by a questionnaire.Results. ANA positivity was found in 66/93 children (71%), anti-ENA in 4/93 (4.3%), anti-dsDNA in 1/93 (1.1%), RF in 3/93 (3.2%), and anti-CCP in none. No significant differences were found between the ANA-positive and ANA-negative groups with respect to age, sex, L-thyroxine treatment, or prevalence of other autoimmune diseases. Overall, parental autoimmunity was found in 23%.Conclusions. ANA positivity was demonstrated in 71% of children with AITD. ANA positivity was not related to overt immune-rheumatic diseases. However, because the positivity of ANA can occur even many years before the onset of systemic autoimmune diseases, prospective studies are warranted.

FRI0600 DIAGNOSTIC VALUE OF SERUM CONNECTIVE TISSUE GROWTH FACTOR IN RHEUMATOID ARTHRITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 906-907
Author(s):  
R. Jiaqi ◽  
J. Zhao ◽  
L. Sun ◽  
Z. MA ◽  
X. Wang
Keyword(s):  
Rheumatoid Arthritis ◽  
Growth Factor ◽  
Interstitial Lung Disease ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Rheumatic Diseases ◽  
Diagnostic Value ◽  
Tissue Growth ◽  
Healthy Controls ◽  
Healthy Individuals

Background:Many autoantibodies are found in the serum of rheumatoid arthritis (RA) patients, including RF, ACPA and so on, which are essential for the disease diagnosis and prognosis judgment. However, 20-30% of patients are still seronegative, so more investigations are needed to find new biomarkers in RA.Objectives:To investigate the prevalence of serum connective tissue growth factor (CTGF) and the association with the clinical features in RA patients.Methods:Serum samples were obtained from 180 patients with RA, 168 patients with other rheumatic diseases, including 43 systemic lupus erythematosus (SLE), 34 osteoarthritis (OA), 17 primary Sjögren’s syndrome (pSS), 20 ankylosing spondylitis (AS), 23 psoriatic arthritis (PsA), 6 reactive arthritis (ReA), 20 systemic sclerosis (SSc), and 5 systemic vasculitis (SV), and 64 healthy individuals in Peking University Third Hospital. The clinical and laboratory data of patients with RA were collected. Levels of CTGF in serum were measured by ELISA. The cut-off value of CTGF was determined by 95 percent of the concentration of the healthy controls. Statistical analyses were performed using the SPSS 24.0 software. Associations between CTGF and the clinical features of RA were evaluated.Results:The prevalence of serum CTGF among RA patients (33.89%) was significantly higher than those of SLE (9.3%), OA (0%), AS (0%), pSS (0%), PsA (0%), ReA (0%), SSc(5%), SV(0%) and healthy controls (4.69%) (p<0.0001). The mean titer of serum CTGF in RA was also significantly higher than those in other rheumatic diseases and healthy controls (p<0.001). At the cutoff value of 264.30 pg/ml, the sensitivity, specificity, positive predictive value and negative predictive value of serum CTGF for RA were 33.89%, 96.55%, 88.41% and 55.45% respectively. Anti-cyclic citrullinated peptide (CCP) antibody (p<0.001), rheumatoid factor (p<0.001), IgG (p=0.025) and IgM (p=0.004) in CTGF-positive patients were higher than those in CTGF-negative patients. Besides, more patients with interstitial lung disease (ILD) were found in CTGF-positive RA.Conclusion:Serum CTGF, as a novel biomarker, has certain diagnostic value for RA. Further studies are necessary to get more knowledge for the diagnostic performance of CTGF in RA.References:[1] Ramazani Y, et al. (2018) Connective tissue growth factor (CTGF) from basics to clinics. Matrix Biol 68-69:44-66.[2] Nozawa K, F et al. (2009) Connective tissue growth factor promotes articular damage by increased osteoclastogenesis in patients with rheumatoid arthritis. Arthritis research & therapy 11 (6):R174.[3] Yang X, et al. (2017) Serum connective tissue growth factor is a highly discriminatory biomarker for the diagnosis of rheumatoid arthritis. Arthritis research & therapy 19 (1):257.[4] Wei JL, et al. (2018) Role of ADAMTS-12 in Protecting Against Inflammatory Arthritis in Mice By Interacting With and Inactivating Proinflammatory Connective Tissue Growth Factor. Arthritis & rheumatology (Hoboken, NJ) 70 (11):1745-1756.[5] Tang X, et al. (2018) Connective tissue growth factor contributes to joint homeostasis and osteoarthritis severity by controlling the matrix sequestration and activation of latent TGFbeta. Ann Rheum Dis 77 (9):1372-1380.Fig 1.Distribution of serum CTGF in RA, other rheumatic diseases and healthy control. Serum sample were from 180 patients with rheumatoid arthritis (RA), 168 patients with other rheumatic diseases and 64 healthy individuals (HC). Levels of serum CTGF were measured by CTGF ELISA kit. The cut-off value was 263.30 pg/mL (black horizontal dotted line); ***p <0.001Table 1. Demographic, clinical and laboratory features of total RA patients and grouped with serum CTGF.Abbreviations: RA=rheumatoid arthritis; SJC=swollen joint count; TJC=tender joint count; ESR=erythrocyte sedimentation rate; CRP=C-reactive protein; DAS=disease activity score; CCP=cyclic citrullinated peptid; RF=rheumatoid factor. CTGF=connective tissue growth factor; ILD= interstitial lung diseaseDisclosure of Interests:None declared

scholarly journals Congenital and neonatal lupus erythematosus: two case reports

2012 ◽  
Vol 87 (4) ◽  
pp. 625-628
Author(s):  
Marcos Noronha Frey ◽  
Ana Elisa Empinotti Ioppi ◽  
Gabriela Czarnobay Garbin ◽  
Roque Domingos Furian ◽  
Ana Elisa Kiszewski Bau
Keyword(s):  
Lupus Erythematosus ◽  
Antinuclear Antibodies ◽  
Case Reports ◽  
Nuclear Antigen ◽  
Neonatal Lupus ◽  
Cutaneous Lesions ◽  
Neonatal Lupus Erythematosus ◽  
Extractable Nuclear Antigen ◽  
The Moment ◽  
Congenital Variant

Neonatal lupus erythematosus is an autoimmune disease produced by the passage of maternal antinuclear antibodies and extractable nuclear antigen antibodies through the placenta. At the moment of the diagnosis, the mothers are asymptomatic in 40 to 60% of cases. The most common manifestations are cutaneous lesions and congenital heart block. The cutaneous findings are variable and usually begin within the first weeks or months of life. Congenital lupus erythematosus is a congenital variant of neonatal lupus erythematosus. We present one case of congenital lupus erythematosus and one case of neonatal lupus erythematous, showing the variability of this disease.

scholarly journals Relationship of profiles of antinuclear antibodies and cytokines in systemic lupus erythematosus

2019 ◽  
Vol 3 (22) ◽  
pp. 37-42
Author(s):  
E. N. Aleksandrova ◽  
A. A. Novikov ◽  
Zh. G. Verizhnikova ◽  
T. A. Panafidina ◽  
G. V. Lukina
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Disease Activity ◽  
Lupus Erythematosus ◽  
Antinuclear Antibodies ◽  
Systemic Autoimmune Disease ◽  
Systemic Lupus ◽  
Gm Csf ◽  
Healthy Donors ◽  
Relationship Of ◽  
Antibodies To Dsdna

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by pathological activation of the innate and acquired immune response, the formation of antinuclear antibodies (ANA), and dysregulation of cytokine production. Objective: to study the relationship of ANA and cytokine profiles in patients with SLE using multiplex immune analysis (MIA) of these biomarkers. We examined 94 patients with SLE (SLICC diagnosis criteria, 2012) and 28 healthy donors. Profiles of ANA and cytokines in blood serum were determined on the basis of suspension microarray technology xMAP. In SLE, antibodies to dsDNA (52.1 %), nucleosomes (54.3 %) and SS-A/Ro (37.2 %), less often to Sm (28.7 %), RibP (14, 9 %), RNP-70 (13.8 %) and SS-B/La (11.7 %). Disease activity (SLEDAI-2K) positively correlated with the concentration of antibodies to dsDNA (r = 0.6), nucleosomes (r = 0.7), Sm (r = 0.4) and RibP (r = 0.3) (p < 0.05). In the sera of patients with SLE, an increase in the levels of IL-4, -6, -8, -12, GM-CSF, MCP-1, MIP-1β, RANTES and a decrease in the content of IL-1β, IL-1ra, IL-2, IL-9, IL-10, eotaxin, G-CSF, IFN-γ, MIP-1α, TNF-α, FGF, PDGF-BB, VEGF compared to donors (p < 0.05). An increase in the concentration of IP-10 and MCP-1 was associated with high disease activity (r = 0.4; r = 0.3; p < 0.05), hyperproduction of antibodies to dsDNA (r = 0.3), nucleosomes (r = 0.5), Sm (r = 0.5), SS-B/La (r = 0.3), RibP (r = 0.4) (p < 0.05) and antibodies to Sm (r = 0.3), SS-B/La (r = 0.3), RibP (r = 0.3) (p < 0.05), respectively.Conclusion: the formation of ANA and high activity of SLE are associated with the overexpression of chemokines IP-10 and MCP-1 induced by IFN. 

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.

scholarly journals DIAGNOSTIC VALUE OF SYSTEMIC LUPUS ERYTHEMATOSUS CLASSIFICATION CRITERIA (AMERICAN COLLEGE OF RHEUMATOLOGY, 1997)

2020 ◽  
pp. 17-22
Author(s):  
U. Abrahamovych ◽  
O. Abrahamovych ◽  
O. Nadashkevych ◽  
A. Svintsitskyi ◽  
O. Synenkyi
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Antinuclear Antibodies ◽  
Clinical Laboratory ◽  
Statistical Significance ◽  
Diagnostic Value ◽  
Systemic Lupus ◽  
American College Of Rheumatology ◽  
Neurologic Disorders

The criteria for the classification of systemic lupus erythematosus were proposed in 1971 by the American College of Rheumatology. They have been clarified since then, but need to be revised.Objective. To determine the diagnostic value of the criteria for the classification of systemic lupus erythematosus proposed by the American College of Rheumatology.Materials and methods. 370 patients (331 women (89.46%) and 39 men (10.54%), average age 41.24 ± 0.63 years) with SLE and 234 patients (150 women (64.10%) and 84 men (35.90%), average age 48.82 ± 0.85 years) with other rheumatic diseases (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis) were randomly enrolled into the study. The patients had undergone comprehensive clinical-laboratory and instrumental examinations in 2010–2018 before they received treatment. The analysis was conducted in MS Excel and SPSS by constructing contingency tables and calculating indicators of diagnostic value.Results. We identified the following criteria as those that can with statistical significance predict the presence of systemic lupus erythematosus: butterfly rash, photosensitivity, serositis (pleuritis, pericarditis), neurologic disorders (seizures, psychosis), thrombocytopenia, renal disorders (proteinuria, cylindruria), anti-dsDNA and antinuclear antibodies.

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