title: The significance of autoantibodies to DFS70/LEDGFp75 in health and disease: integrating basic science with clinical understanding.
abstract: Antinuclear autoantibodies (ANAs) displaying the nuclear dense fine speckled immunofluorescence (DFS-IIF) pattern in HEp-2 substrates are commonly observed in clinical laboratory referrals. They target the dense fine speckled autoantigen of 70 kD (DFS70), most commonly known as lens epithelium-derived growth factor p75 (LEDGFp75). Interesting features of these ANAs include their low frequency in patients with systemic autoimmune rheumatic diseases (SARD), elevated prevalence in apparently healthy individuals, IgG isotype, strong trend to occur as the only ANA specificity in serum, and occurrence in moderate to high titers. These autoantibodies have also been detected at varied frequencies in patients with diverse non-SARD inflammatory and malignant conditions such as atopic diseases, asthma, eye diseases, and prostate cancer. These observations have recently stimulated vigorous research on their clinical and biological significance. Some studies have suggested that they are natural, protective antibodies that could serve as biomarkers to exclude a SARD diagnosis. Other studies suggest that they might be pathogenic in certain contexts. The emerging role of DFS70/LEDGFp75 as a stress protein relevant to human acquired immunodeficiency syndrome, cancer, and inflammation also points to the possibility that these autoantibodies could be sensors of cellular stress and inflammation associated with environmental factors. In this comprehensive review, we integrate our current knowledge of the biology of DFS70/LEDGFp75 with the clinical understanding of its autoantibodies in the contexts of health and disease.
authors.affiliation: Ventana Medical, Roche Tissue Diagnostics, Tucson, AZ, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Ochs
authors.affiliation: Department of Research, Inova Diagnostics, Inc., San Diego, CA, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Mahler
authors.affiliation: Department of Basic Sciences, Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Mortensen Hall 142, 11085 Campus St, Loma Linda, CA, 92350, USA.
authors.forename: Anamika
authors.initials: A
authors.lastname: Basu
authors.affiliation: Department of Basic Sciences, Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Mortensen Hall 142, 11085 Campus St, Loma Linda, CA, 92350, USA.
authors.forename: Leslimar
authors.initials: L
authors.lastname: Rios-Colon
authors.affiliation: Department of Basic Sciences, Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Mortensen Hall 142, 11085 Campus St, Loma Linda, CA, 92350, USA.
authors.forename: Tino W
authors.initials: TW
authors.lastname: Sanchez
authors.affiliation: Rheumatology Division, Universidade Federal de Sao Paulo, and Immunology Division, Fleury Medicine and Health Laboratories, São Paulo, Brazil.
authors.forename: Luis E
authors.initials: LE
authors.lastname: Andrade
authors.affiliation: Faculty of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Fritzler
authors.affiliation: Department of Basic Sciences, Center for Health Disparities and Molecular Medicine, Loma Linda University School of Medicine, Mortensen Hall 142, 11085 Campus St, Loma Linda, CA, 92350, USA. ccasiano@llu.edu.|Department of Medicine, Division of Rheumatology, Loma Linda University School of Medicine, Loma Linda, CA, USA. ccasiano@llu.edu.
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Casiano
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000276:immunology*; D001323:Autoantibodies / Q000097:blood*; D006801:Humans; D014157:Transcription Factors / Q000276:immunology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001323:Autoantibodies; C504649:PSIP1 protein, human; D014157:Transcription Factors
keywords: Antinuclear autoantibodies; Autoimmunity; DFS70/LEDGFp75; Inflammation; Stress