Clinical significance of anti-dense fine speckled 70 antibody in patients with fibromyalgia

Abstract

Antinuclear antibodies (ANAs) are a serological hallmark in the diagnosis of systemic autoimmune rheumatic diseases (SARD). The indirect immunofluorescence (IIF) assay on HEp-2 cells is a commonly used test for the detection of ANA and has been recently recommended as the screening test of choice by a task force of the American College of Rheumatology. However, up to 20% of apparently healthy individuals (HI) have been reported to have a positive IIF ANA test, primarily related to autoantibodies that target the dense fine speckles 70 (DFS70) antigen. Even more important, the DFS IIF pattern has been reported in up to 33% of ANA positive HI, but not in ANA positive SARD sera. Since the intended use of the ANA HEp-2 test is to aid in the diagnosis and classification of SARD, the detection and reporting of anti-DFS70 antibodies and their associated pattern (DFS) as a positive test significantly reduce the specificity and the positive likelihood of the ANA test. This has significant implications for medical management and diagnostic algorithms involving the detection of ANA. Recently, a novel immunoadsorption method has been developed that specifically blocks anti-DFS70 antibodies and, therefore, significantly increases the specificity of the ANA test for SARD. This immunoadsorption method has the potential to overcome a significant limitation of the ANA HEp-2 assay. The present paper summarizes the current knowledge about anti-DFS70 antibodies and their clinical impact on ANA testing.

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

“…The report by Muro et al in 2004 that anti-DFS70/ LEDGF autoantibodies were present at a frequency of 10.7%, with a broad titer range, in apparently healthy individuals (HI) was the preamble to several studies from laboratories around the world reporting elevated frequencies of these antibodies in HI compared to patients with SARD [101][102][103][104][105][106][107]. It has become evident recently that this elevated frequency of anti-DFS70/LEDGF antibodies in HI relative to SARD is influenced by multiple factors, including geography, gender, age, detection assays, and care setting [108][109][110].…”

“…However, a distinctive feature of these antibodies in HI individuals is their relatively elevated frequencies as monospecific antibodies (only ANA detectable in the serum by HEp-2 IIFA), in contrast to patients with SARD in which these antibodies tend to appear concomitantly with other diseaseassociated ANAs [111][112][113]. These observations have led to the hypothesis that monospecific anti-DFS70/LEDGF autoantibodies may be considered as negative biomarkers to exclude a SARD diagnosis [100][101][102][103][104][105][106][107][110][111][112][113][114][115].…”

“…As mentioned above, while the prevalence of anti-DFS70/ LEDGF antibodies seems to be comparable in both HI and patients with SARD, typically ranging from 0 to 11% in both groups [70,92,95], they differ in their exclusivity, with monospecific antibodies more prevalent in HI than in patients with SARD [100][101][102][103][104][105][106][107][110][111][112][113][114][115]. However, monospecific anti-DFS70/LEDGF antibodies are not completely absent in SARD, since a recent international multicenter study led by Marvin Fritzler found a 1.1% frequency of these monospecific antibodies in a large cohort of patients with systemic lupus erythematosus (SLE) (13 out of 1137 patients) [127].…”

The Interplay of Mitochondrial Oxidative Stress and Endoplasmic Reticulum Stress in Cardiovascular Fibrosis in Obese Rats

“…A variety of factors has been suggested as potential mediators of cardiac fibrosis in the context of obesity, including oxidative stress [ 4 , 5 , 6 ]. Mitochondria are the main source of reactive oxygen species (ROS) in the cell through oxidative phosphorylation (OXPHOS) during the process of ATP synthesis [ 7 ].…”

Musculoskeletal Manifestations in Sjogren’s Syndrome: An Orthopedic Point of View

“…In a recent study of Applbaum et al, the authors found a link between autoantibodies and FM, as one-third of its FM patients with sicca syndrome and/or xerostomia tested positive for Sjögren’s syndrome biomarkers, and the majority of these were also positive for one or more tissue-specific autoantibodies [ 48 ]. Additionally, Jeong et al reported the detection of anti-dense fine-speckled 70 antibodies in FM patients, with significantly higher levels being found specifically in patients with arthralgia and sleep disturbances [ 49 ]. Torrente-Segara et al, in their study on 437 pSS patients, reported a 14.6% of FM prevalence.…”