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FRI0565 The Presence of Anti-DFS70 Antibodies Suggests Absence of Connective Tissue Diseases in Patients with Anti-Nuclear Antibodies (ANA)
  1. K. Conrad1,
  2. U. Höpner1,
  3. N. Röber1,
  4. M. Aringer2,
  5. S. Rudolph3,
  6. A. Gräßler4,
  7. K. Lüthke5,
  8. L. Unger6,
  9. M. Mahler7
  1. 1Institute of Immunology, Medical Faculty of TUD
  2. 2Department of Medicine III, University Hospital Carl Gustav Carus Dresden, Dresden
  3. 3Department of Internal Medicine and Rheumatology, Zeisigwaldkliniken Bethanien Chemnitz, Chemnitz
  4. 4Medical Practice, Pirna
  5. 5Medical Practice of Rheumatology
  6. 6Medical Department of Medicine I, Municipal Hospital Dresden-Friedrichstadt, Dresden, Germany
  7. 7Inova Diagnostics Inc., San Diego, United States

Abstract

Background Antinuclear antibodies (ANA) determined by the HEp-2 cell assay are the primary screening test for connective tissue diseases (CTDs), i.e. systemic lupus erythematosus (SLE), mixed connective tissue disease (MCTD), Sjögrens's syndrome (SjS), systemic sclerosis (SSc) and idiopathic inflammatory myopathies (IIM). While ANA have high sensitivity, their specificity is low, because ANA are detectable also in patients with other diseases and even in apparently healthy individuals. Therefore, positive ANA may lead to additional testing and potentially even inappropriate treatment in patients with musculoskeletal symptoms not caused by CTDs. It has been shown that autoantibodies directed against DFS70 are common among ANA positive individuals with no evidence of CTDs [1]. However, further studies are needed to confirm these results.

Objectives To study a large cohort of CTD patients and different non-CTD cohorts to adress this issue by using a novel chemoluminescence assay (CIA) for quantifiable and standardized determination of anti-DFS70 antibodies.

Methods A routine cohort of 217 ANA positive patients without antibodies to dsDNA, nucleosomes, histones or topoisomerase (Scl-70) and a CTD cohort of 379 patients (219 SLE, 108 SSc, 52 IIM) were collected. As control groups, 387 patients without CTDs (300 patients with other autoimmune diseases and 87 patient with atopic diseases) and 192 healthy individuals were assorted. All samples were tested for anti-DFS70 antibodies using QUANTA Flash DFS70 chemiluminescent immunoassay (CIA, Inova Diagnostics, San Diego, USA).

Results Of the 217 selected routine sera, 163 showed the typical DFS pattern in the HEp-2 cell assay and 62 (28.6%) were positive for anti-DFS70 by CIA. All of the DFS70 antibody positive sera showed the unique DFS pattern. Of the anti-DFS70 positive patients in this routine cohort, 61 had “nonspecific” rheumatic symptoms but no CTD (with or without defined diseases such as Hashimoto's thyroiditis). Only one patient with anti-DFS70 antibodies was diagnosed as probable SLE in the absence of SLE specific autoantibodies. In blood donors, anti-DFS70 antibodies occur with a prevalence of 7%, which was significantly higher than in the CTD and non-CTD groups of autoimmune and allergic diseases (9/766, 1.2%, p<0.0001). Only two of the 379 patients from the CTD group (0.5%) were positive for anti-DFS70 antibodies by CIA. These two anti-DFS70 positive patients also had disease specific antibodies (anti-Scl-70 in one SSc patient and anti-Mi2 in one IIM patient).

Conclusions Antibodies to DFS70 are frequently observed in ANA positive sera in the absence of CTD-specific autoantibodies. Testing for anti-DFS70 antibodies may be helpful in defining an ANA positive subgroup with a low likelihood of CTDs.

References

  1. Mahler M, Hanly JG, Fritzler MJ. Importance of the dense fine speckled pattern on HEp-2 cells and anti-DFS70 antibodies for the diagnosis of systemic autoimmune diseases. Clin Dev Immunol 2012; Article ID 4943356.

Disclosure of Interest None declared

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