Low copy numbers of complement and deficiency are risk factors for myositis, its subgroups and autoantibodies

Authors

• Danlei Zhou, Center for Microbial Pathogenesis, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio, USA.
• Emily H. King, Center for Microbial Pathogenesis, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio, USA.
• Simon Rothwell, National Institute for Health Research Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, The University of Manchester, Manchester, UK.
• Olga Krystufkova, Institute of Rheumatology and Department of Rheumatology, Charles University, Prague, Czech Republic.
• Antonella Notarnicola, Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, University Hospital Karolinska, Stockholm, Sweden.
• Samantha Coss, Center for Microbial Pathogenesis, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio, USA.
• Rabheh Abdul-Aziz, Division of Rheumatology, Nationwide Children's Hospital and Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
• Katherine E. Miller, Center for Microbial Pathogenesis, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio, USA.
• Amanda Dang, Center for Microbial Pathogenesis, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio, USA.
• G Richard Yu, Center for Microbial Pathogenesis, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio, USA.
• Joanne Drew, Division of Rheumatology, Nationwide Children's Hospital and Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
• Emeli Lundström, Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, University Hospital Karolinska, Stockholm, Sweden.
• Lauren M. Pachman, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.
• Gulnara Mamyrova, Division of Rheumatology, Department of Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
• Rodolfo V. Curiel, Division of Rheumatology, Department of Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
• Boel De Paepe, Department of Neurology, Ghent University Hospital, Ghent, Belgium.
• Jan L. De Bleecker, Department of Neurology, Ghent University Hospital, Ghent, Belgium.
• Antony Payton, Division of Informatics, Imaging and Data Sciences, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
• William Ollier, Faculty of Science and Engineering, Manchester Metropolitan University, Manchester, UK.
• Terrance P. O'Hanlon, Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Bethesda, MD, USA.
• Ira N. Targoff, Veteran's Affairs Medical Center, University of Oklahoma Health Sciences Center, and Oklahoma Medical Research Foundation, Oklahoma City, OK, USA.
• Willy A. Flegel, Department of Transfusion Medicine, NIH Clinical Center, National Institutes of Health, Bethesda, MD, USA.
• Vidya Sivaraman, Division of Rheumatology, Nationwide Children's Hospital and Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
• Edward Oberle, Division of Rheumatology, Nationwide Children's Hospital and Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
• Shoghik Akoghlanian, Division of Rheumatology, Nationwide Children's Hospital and Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
• Kyla Driest, Division of Rheumatology, Nationwide Children's Hospital and Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
• Charles H. Spencer, University of Mississippi Medical Center, Jackson, Mississippi, USA.
• Yee Ling Wu, Division of Rheumatology, Nationwide Children's Hospital and Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
• Haikady N. Nagaraja, Division of Biostatistics, The Ohio State University, Columbus, Ohio, USA.
• Stacy P. Ardoin, Division of Rheumatology, Nationwide Children's Hospital and Department of Pediatrics, The Ohio State University, Columbus, Ohio, USA.
• Hector Chinoy, National Institute for Health Research Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, The University of Manchester, Manchester, UK.
• Lisa G. Rider, Environmental Autoimmunity Group, Clinical Research Branch, National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, Bethesda, MD, USA.

Document Type

Journal Article

Publication Date

9-28-2022

Journal

Annals of the rheumatic diseases

DOI

10.1136/ard-2022-222935

Keywords

autoantibodies; dermatomyositis; polymyositis

Abstract

BACKGROUND: Idiopathic inflammatory myopathies (IIM) are a group of autoimmune diseases characterised by myositis-related autoantibodies plus infiltration of leucocytes into muscles and/or the skin, leading to the destruction of blood vessels and muscle fibres, chronic weakness and fatigue. While complement-mediated destruction of capillary endothelia is implicated in paediatric and adult dermatomyositis, the complex diversity of complement in IIM pathology was unknown. METHODS: We elucidated the gene copy number (GCN) variations of total , and and in 1644 Caucasian patients with IIM, plus 3526 matched healthy controls using real-time PCR or Southern blot analyses. Plasma complement levels were determined by single radial immunodiffusion. RESULTS: The large study populations helped establish the distribution patterns of various GCN groups. Low GCNs of (=2+3) and deficiency (=0+1) were strongly correlated with increased risk of IIM with OR equalled to 2.58 (2.28-2.91), p=5.0×10 for , and 2.82 (2.48-3.21), p=7.0×10 for deficiency. Contingency and regression analyses showed that among patients with deficiency, the presence of became insignificant as a risk factor in IIM except for inclusion body myositis (IBM), by which 98.2% had with an OR of 11.02 (1.44-84.4). Intragroup analyses of patients with IIM for C4 protein levels and IIM-related autoantibodies showed that those with anti-Jo-1 or with anti-PM/Scl had significantly lower C4 plasma concentrations than those without these autoantibodies. CONCLUSIONS: deficiency is relevant in dermatomyositis, is important in IBM and both deficiency and contribute interactively to risk of polymyositis.

APA Citation

Zhou, Danlei; King, Emily H.; Rothwell, Simon; Krystufkova, Olga; Notarnicola, Antonella; Coss, Samantha; Abdul-Aziz, Rabheh; Miller, Katherine E.; Dang, Amanda; Yu, G Richard; Drew, Joanne; Lundström, Emeli; Pachman, Lauren M.; Mamyrova, Gulnara; Curiel, Rodolfo V.; De Paepe, Boel; De Bleecker, Jan L.; Payton, Antony; Ollier, William; O'Hanlon, Terrance P.; Targoff, Ira N.; Flegel, Willy A.; Sivaraman, Vidya; Oberle, Edward; Akoghlanian, Shoghik; Driest, Kyla; Spencer, Charles H.; Wu, Yee Ling; Nagaraja, Haikady N.; Ardoin, Stacy P.; Chinoy, Hector; and Rider, Lisa G., "Low copy numbers of complement and deficiency are risk factors for myositis, its subgroups and autoantibodies" (2022). GW Authored Works. Paper 1585.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/1585

Department

Medicine