title: Specificity of antinuclear autoantibodies recognizing the dense fine speckled nuclear pattern: Preferential targeting of DFS70/LEDGFp75 over its interacting partner MeCP2.
abstract: Human antinuclear autoantibodies (ANAs) targeting the dense fine speckled (DFS) nuclear protein DFS70, commonly known as lens epithelium derived growth factor p75 (LEDGFp75), present a clinical puzzle since their significance remains elusive. While their frequencies are low in ANA-positive autoimmune rheumatic diseases, they are relatively elevated in clinical laboratory referrals, diverse inflammatory conditions, and 'apparently' healthy individuals. We reported previously that DFS70/LEDGFp75 is an autoantigen in prostate cancer that closely interacts with another 70kD DFS nuclear protein, methyl CpG binding protein 2 (MeCP2). This led us to investigate if anti-DFS sera exclusively target DFS70/LEDGFp75 or also recognize MeCP2. Using several complementary autoantibody detection platforms and cellular/molecular approaches we evaluated 65 human sera producing anti-DFS autoantibodies. Our results show that these antibodies are highly specific for DFS70/LEDGFp75 and do not target MeCP2. Establishing the specificity of anti-DFS autoantibodies has implications for increasing our understanding of their biological significance and clinical utility.
authors.affiliation: Center for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Anamika
authors.initials: A
authors.lastname: Basu
authors.affiliation: Center for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Leanne
authors.initials: L
authors.lastname: Woods-Burnham
authors.affiliation: Center for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Greisha
authors.initials: G
authors.lastname: Ortiz
authors.affiliation: Center for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Leslimar
authors.initials: L
authors.lastname: Rios-Colon
authors.affiliation: Center for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, USA.
authors.forename: Johnny
authors.initials: J
authors.lastname: Figueroa
authors.affiliation: Department of Research, Inova Diagnostics, Inc., San Diego, CA, USA.
authors.forename: Roger
authors.initials: R
authors.lastname: Albesa
authors.affiliation: Rheumatology Division, Universidade Federal de Sao Paulo, Immunology Division, Fleury Medicine and Health Laboratories, Sao Paulo, Brazil.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Andrade
authors.affiliation: Department of Research, Inova Diagnostics, Inc., San Diego, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mahler
authors.affiliation: Center for Health Disparities and Molecular Medicine, Department of Basic Sciences, Loma Linda University School of Medicine, Loma Linda, CA, USA; Department of Medicine, Division of Rheumatology, Loma Linda University School of Medicine, Loma Linda, CA, USA. Electronic address: ccasiano@llu.edu.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Casiano
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000276:immunology*; D000974:Antibodies, Antinuclear / Q000097:blood / Q000276:immunology*; D000918:Antibody Specificity / Q000276:immunology*; D045744:Cell Line, Tumor; D006801:Humans; D015151:Immunoblotting; D051783:Methyl-CpG-Binding Protein 2 / Q000276:immunology*; D018613:Microscopy, Confocal; D011485:Protein Binding / Q000276:immunology; D034622:RNA Interference; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000974:Antibodies, Antinuclear; D051783:Methyl-CpG-Binding Protein 2; C504649:PSIP1 protein, human; D014157:Transcription Factors
keywords: Autoantibodies; Autoimmunity; DFS70; Dense fine speckles; LEDGFp75; MeCP2