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Mahler M.,INOVA Diagnostics Inc. | Meroni P.L.,University of Milan | Andrade L.E.,Federal University of Sao Paulo | Khamashta M.,Kings College London | And 3 more authors.
Autoimmunity Reviews | Year: 2016

Anti-DFS70 antibodies and their clinical associations remain an immunological paradox. Unlike other antinuclear antibodies (ANA), especially when present at high titres, anti-DFS70 antibodies are not prevalent in ANA associated rheumatic diseases. Despite significant interest and progress in understanding the clinical association of anti-DFS70 antibodies, no specific clinical associations have been confirmed. In reality, several studies reporting clinical association of these antibodies (i.e. atopic dermatitis, thrombosis, autoimmune thyroiditis) have added confusion instead of bringing significant insight. In addition, several groups have consistently reported on the occurrence of anti-DFS70 antibodies in a relevant fraction of apparently healthy individuals. This review aims to analyse the current knowledge and to provide future guidance to analyse potential clinical associations of anti-DFS70 antibodies by summarizing and interpreting recent findings. © 2015 Elsevier B.V. Source


Tonutti E.,Immunopathology and Allergology | Bizzaro N.,Laboratory of Clinical Pathology
Autoimmunity Reviews | Year: 2014

Celiac disease is a complex disorder, the development of which is controlled by a combination of genetic (HLA alleles) and environmental (gluten ingestion) factors. New diagnostic guidelines developed by ESPGHAN emphasize the crucial role of serological tests in the diagnostic process of symptomatic subjects, and of the detection of HLA DQ2/DQ8 alleles in defining a diagnosis in asymptomatic subjects belonging to at-risk groups. The serological diagnosis of CD is based on the detection of class IgA anti-tissue transglutaminase (anti-tTG) and anti-endomysial antibodies. In patients with IgA deficiency, anti-tTG or anti-deamidated gliadin peptide antibody assays of the IgG class are used. When anti-tTG antibody levels are very high, antibody specificity is absolute and CD can be diagnosed without performing a duodenum biopsy. Non-celiac gluten sensitivity is a gluten reaction in which both allergic and autoimmune mechanisms have been ruled out. Diagnostic criteria include the presence of symptoms similar to those of celiac or allergic patients; negative allergological tests and absence of anti-tTG and EMA antibodies; normal duodenal histology; evidence of disappearance of the symptoms with a gluten-free diet; relapse of the symptoms when gluten is reintroduced. © 2014 Elsevier B.V. Source


Bizzaro N.,Laboratory of Clinical Pathology | Villalta D.,Allergology and ClinicaI Immunology | Giavarina D.,San Bortolo Hospital | Tozzoli R.,Clinical Pathology Laboratories
Autoimmunity Reviews | Year: 2012

Background: Methods to detect anti-nucleosome antibodies (ANuA) have been available for more than 10. years and the test has demonstrated its good sensitivity and high specificity in diagnosing systemic lupus erythematosus (SLE). Despite these data produced through clinical and laboratory research, the test is little used. Objective: To verify the diagnostic performance of methods for measuring ANuA and to compare them with those for anti-dsDNA antibodies. Data sources: A systematic review of English and non-English articles using MEDLINE and EMBASE with the search terms "nucleosome", "chromatin", "anti-nucleosome antibodies" and "anti-chromatin antibodies". Additional studies were identified checking reference lists in the selected articles. Study selection: We selected studies reporting on anti-nucleosome tests performed by quantitative immunoassays, on patients with SLE as the index disease (sensitivity) and a control group (specificity).A total of 610 titles were initially identified with the search strategy described. 548 publications were subsequently excluded based on abstract and title. Full-text review was undertaken as the next step on 62 publications providing data on anti-nucleosome testing; 25 articles were then excluded because they did not include either SLE patients or a control group, and 37 articles were selected for the metanalysis. Finally, a sub-metanalysis study was conducted on the 26 articles providing data on both ANuA and anti-dsDNA antibody assays in the same series of patients. Data extraction: Extraction of data from selected articles was performed by two authors independently, using predefined criteria: the number of patients with SLE as the index case, and the number of healthy or diseased controls; specification of the analytical method used to detect anti-nucleosome and anti-dsDNA antibodies; the cut-off used in the study; and the sensitivity and specificity of the assay. Demographic and clinical data on the population investigated (adults or children; lupus patients with or without nephritis; patients with active or inactive disease) were also recorded and analyzed in a separate evaluation. Results: The systematic review and metanalysis showed that the overall sensitivity of the ANuA assay is 61% (confidence interval-CI, 60-62) and the specificity 94% (CI, 94-95). The overall positive likelihood ratio is 13.81 (CI, 9.05-21.09) and the negative likelihood ratio 0.38 (CI, 0.33-0.44). The odds ratio for having SLE in ANuA-positive patients is 40.7. The comparative analysis on anti-dsDNA antibodies conducted on the 26 studies which provided data for both antibodies showed that ANuA have greater diagnostic sensitivity (59.9% vs 52.4%) and a specificity rating only slightly higher (94.9% vs 94.2%). The probability that a subject with positive ANuA have SLE is 41 times greater than a subject with negative ANuA, while for anti-dsDNA the probability is 28 times greater. These figures are even more impressive in children, in whom ANuA have an odds ratio for the diagnosis of SLE of 146, compared to 51 for anti-dsDNA antibodies. In selected studies, ANuA (p<0.0001) but not anti-dsDNA antibodies (p=0.256) were significantly associated with disease activity measured by the international score systems. However, neither antibody appears to correlate with kidney involvement. Conclusions: Data from the metanalysis have shown that ANuA have equal specificity but higher sensitivity and prognostic value than anti-dsDNA antibodies in the diagnosis of SLE. Despite a certain heterogeneity among the various studies, the use of ANuA appears more efficacious than anti-dsDNA. © 2012 Elsevier B.V. Source


Tampoia M.,University of Bari | Giavarina D.,Clinical Chemistry and Hematology Laboratory | Di Giorgio C.,University of Bari | Bizzaro N.,Laboratory of Clinical Pathology
Autoimmunity Reviews | Year: 2012

Background: Systematic reviews and meta-analysis are essential tools to accurately and reliably summarize evidence, and can be used as a starting point for developing practice guidelines for the diagnosis and treatment of patients. Aim: To estimate the diagnostic accuracy of enzyme-linked immunosorbent assays (ELISA) to detect anti-BP180 and anti-desmoglein 3 (Dsg3) autoantibodies in the diagnosis of autoimmune blistering skin diseases. Methods: A Medline search of English written articles, published between 1994 and 2011, reporting data on the sensitivity and specificity of diagnostic tests was conducted using the following search terms: "BP180 autoantibodies", "Dsg3 autoantibodies", and "enzyme linked immunosorbent assay". The selected articles have been evaluated according to the quality of the statistical methods used to calculate diagnostic accuracy (definition of cutoff value, use of ROC curves, and selection of control cases). The meta-analysis was performed using a summary ROC (SROC) curve and a random-effect model to independently combine sensitivity and specificity across studies. Results: The search yielded 69 publications on BP180 autoantibodies and 178 on Dsg3 autoantibodies. A total of 30 studies met the inclusion criteria: 17 provided data on the assays to detect autoantibodies to BP180 in a sample of 583 patients with bullous pemphigoid (BP), while 13 studies provided data on the assays to search for anti-Dsg3 autoantibodies in a sample of 1058 patients with pemphigus vulgaris (PV). The 17 studies on BP180 autoantibodies yielded a pooled sensitivity of 0.87 (95% confidence interval (CI) 0.85 to 0.89) and a pooled specificity of 0.98 (CI, 0.98 to 0.99). The area under the curve (AUC) for the SROC curve was 0.988, and the summary diagnostic odds ratio was 374.91 (CI, 249.97 to 562.30). The 13 studies on Dsg3 autoantibodies which met the inclusion criteria, yielded a pooled sensitivity of 0.97 (CI, 0.95 to 0.98), and a pooled specificity of 0.98 (CI, 0.98 to 0.99). The AUC for the SROC curve was 0.995 and the summary diagnostic odds ratio was 1466.11 (95% CI, 750.36 to 2864.61). Conclusions: Results of the meta-analysis demonstrated that ELISA tests for anti-BP180 and anti-Dsg3 autoantibodies have high sensitivity and specificity for BP and PV, respectively, and can be used in daily laboratory practice for the initial diagnosis of autoimmune blistering skin diseases. © 2012 Elsevier B.V. Source


Fabris M.,University of Udine | Zago S.,University of Udine | Tosolini R.,University of Udine | Melli P.,University of Udine | And 2 more authors.
Pediatrics | Year: 2014

Antidense fine speckles 70 (anti-DFS70) antibodies, a peculiar antinuclear antibody (ANA) pattern by indirect immunofluorescence, is frequently observed in ANA-positive individuals with no evidence of systemic autoimmune rheumatic disease. They may be found in many different inflammatory conditions and in healthy individuals. We herein report a case of an 8-year-old girl presenting with generalized edema, hypertension, hepatomegaly, and a history of pharyngitis, which occurred 3 weeks earlier. Laboratory analysis revealed low complement C3 (6 mg/dL), microhematuria, and proteinuria. A diagnosis of acute glomerulonephritis was made. Anti-dsDNA, antiextractable nuclear antigens, and antineutrophil cytoplasmic antibodies were negative. However, a highly positive (1:640) ANA immunofluorescence test with dense fine speckles pattern was found. The presence of anti-DFS70 immunoglobulin G antibodies was confirmed by a specific immunoassay. In conclusion, the presence of isolated anti-DFS70 antibodies may be useful to exclude an autoimmune pathogenesis in those children with a positive ANA test and a clinical picture possibly attributable to systemic autoimmune rheumatic disease. This will avoid further unnecessary investigation with the potential for incorrect diagnosis and possibly harmful treatment. Copyright © 2014 by the American Academy of Pediatrics. Source

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