Michael Mahler1, Minoru Satoh2, Marie Hudson2, Murray Baron2, Jason Y F Chan2, Edward K L Chan2, James Wick2, Marvin J Fritzler2. 1. From INOVA Diagnostics Inc., San Diego, California, USA; the Department of Clinical Nursing, School of Health Sciences, University of Occupational and Environmental Health, Kita-kyushu, Japan; Division of Rheumatology and Clinical Immunology, Department of Medicine, and Pathology, Immunology and Laboratory Medicine, and the Department of Oral Biology, University of Florida, Gainesville, Florida, USA; Department of Medicine, McGill University; the Division of Rheumatology and Lady Davis Institute, Jewish General Hospital, Montréal, Quebec; the Department of Medicine, University of Calgary, Calgary, Alberta, Canada.M. Mahler, PhD, INOVA Diagnostics Inc.; M. Satoh, MD, PhD, Department of Clinical Nursing, School of Health Sciences, University of Occupational and Environmental Health, and Division of Rheumatology and Clinical Immunology, Department of Medicine, and Pathology, Immunology and Laboratory Medicine, University of Florida; M. Hudson, MD, Department of Medicine, McGill University, Division of Rheumatology and Lady Davis Institute, Jewish General Hospital; M. Baron, MD, Department of Medicine, McGill University, and Division of Rheumatology, Jewish General Hospital; J.Y.F. Chan; E.K.L. Chan, PhD, Department of Oral Biology, University of Florida; J. Wick, BSc; M.J. Fritzler, MD, PhD, Department of Medicine, University of Calgary. mmahler@inovadx.com m.mahler.job@web.de. 2. From INOVA Diagnostics Inc., San Diego, California, USA; the Department of Clinical Nursing, School of Health Sciences, University of Occupational and Environmental Health, Kita-kyushu, Japan; Division of Rheumatology and Clinical Immunology, Department of Medicine, and Pathology, Immunology and Laboratory Medicine, and the Department of Oral Biology, University of Florida, Gainesville, Florida, USA; Department of Medicine, McGill University; the Division of Rheumatology and Lady Davis Institute, Jewish General Hospital, Montréal, Quebec; the Department of Medicine, University of Calgary, Calgary, Alberta, Canada.M. Mahler, PhD, INOVA Diagnostics Inc.; M. Satoh, MD, PhD, Department of Clinical Nursing, School of Health Sciences, University of Occupational and Environmental Health, and Division of Rheumatology and Clinical Immunology, Department of Medicine, and Pathology, Immunology and Laboratory Medicine, University of Florida; M. Hudson, MD, Department of Medicine, McGill University, Division of Rheumatology and Lady Davis Institute, Jewish General Hospital; M. Baron, MD, Department of Medicine, McGill University, and Division of Rheumatology, Jewish General Hospital; J.Y.F. Chan; E.K.L. Chan, PhD, Department of Oral Biology, University of Florida; J. Wick, BSc; M.J. Fritzler, MD, PhD, Department of Medicine, University of Calgary.
Abstract
OBJECTIVE: Antinuclear antibodies (ANA) occur in up to 95% of patients with systemic sclerosis (SSc). In most, SSc-associated antibodies are detected (i.e., centromere, topoisomerase I, RNA polymerase III, PM/Scl, Ro52/TRIM21, and U1RNP). Ribonuclease P protein subunit p25, (Rpp25) is an autoantigenic component of the Th/To complex. The contribution of anti-Th/To and anti-Rpp25 antibodies to ANA positivity in patients with SSc remains unknown. METHODS: Sera from 873 patients with SSc were tested for ANA, and SSc-associated antibodies were measured. Samples without antibodies to extractable nuclear antigens (ENA; n = 53, ANA+/ENA-), were analyzed by immunoprecipitation (IP) and metabolically labeled proteins and for anti-Rpp25 antibodies (n = 50) by a chemiluminescent immunoassay (CLIA) and Rpp25 ELISA. RESULTS: Anti-Th/To antibodies occurred in 19/53 (36%), as determined by IP, and were the most common autoantibody in ANA+/ENA- SSc. Of those samples, 50/53 were available for additional testing by CLIA and ELISA. Anti-Rpp25 antibodies were detected in 12 (24% CLIA) or 10 (20% ELISA) of 50 patients. Receiver-operating characteristic curve analysis showed similar discrimination between Th/To IP-positive (n = 19) and -negative samples (n = 31) by CLIA and ELISA (area under the curve 0.90 vs 0.87; p = 0.6691). The positive percent agreement between IP and CLIA or ELISA was 12/19 (63.2%, 95% CI 38.4-83.7%) or 10/19 (52.6%, 95% CI 73.3-94.2%), respectively. Negative percent agreement was 100% for both assays. CONCLUSION: Autoantibodies to the Th/To autoantigen are important in patients with SSc who have been considered negative for SSc-specific or SSc-associated antibodies by widely available commercial assays. Rpp25 can be considered a major target of anti-Th/To antibodies. Assays detecting anti-Th/To and anti-Rpp25 antibodies may be important in SSc.
OBJECTIVE: Antinuclear antibodies (ANA) occur in up to 95% of patients with systemic sclerosis (SSc). In most, SSc-associated antibodies are detected (i.e., centromere, topoisomerase I, RNA polymerase III, PM/Scl, Ro52/TRIM21, and U1RNP). Ribonuclease P protein subunit p25, (Rpp25) is an autoantigenic component of the Th/To complex. The contribution of anti-Th/To and anti-Rpp25 antibodies to ANA positivity in patients with SSc remains unknown. METHODS: Sera from 873 patients with SSc were tested for ANA, and SSc-associated antibodies were measured. Samples without antibodies to extractable nuclear antigens (ENA; n = 53, ANA+/ENA-), were analyzed by immunoprecipitation (IP) and metabolically labeled proteins and for anti-Rpp25 antibodies (n = 50) by a chemiluminescent immunoassay (CLIA) and Rpp25 ELISA. RESULTS: Anti-Th/To antibodies occurred in 19/53 (36%), as determined by IP, and were the most common autoantibody in ANA+/ENA- SSc. Of those samples, 50/53 were available for additional testing by CLIA and ELISA. Anti-Rpp25 antibodies were detected in 12 (24% CLIA) or 10 (20% ELISA) of 50 patients. Receiver-operating characteristic curve analysis showed similar discrimination between Th/To IP-positive (n = 19) and -negative samples (n = 31) by CLIA and ELISA (area under the curve 0.90 vs 0.87; p = 0.6691). The positive percent agreement between IP and CLIA or ELISA was 12/19 (63.2%, 95% CI 38.4-83.7%) or 10/19 (52.6%, 95% CI 73.3-94.2%), respectively. Negative percent agreement was 100% for both assays. CONCLUSION: Autoantibodies to the Th/To autoantigen are important in patients with SSc who have been considered negative for SSc-specific or SSc-associated antibodies by widely available commercial assays. Rpp25 can be considered a major target of anti-Th/To antibodies. Assays detecting anti-Th/To and anti-Rpp25 antibodies may be important in SSc.
Authors: Kristina E N Clark; Corrado Campochiaro; Lauren V Host; Alper Sari; Jennifer Harvey; Christopher P Denton; Voon H Ong Journal: Sci Rep Date: 2022-07-02 Impact factor: 4.996
Authors: Christopher A Mecoli; Brittany L Adler; Qingyuan Yang; Laura K Hummers; Antony Rosen; Livia Casciola-Rosen; Ami A Shah Journal: Arthritis Rheumatol Date: 2020-12-26 Impact factor: 10.995