Carolina Muñoz-Grajales1,2, Stephenie D Prokopec3, Sindhu R Johnson4,5, Zahi Touma5,6, Zareen Ahmad4,5, Dennisse Bonilla2, Linda Hiraki7, Arthur Bookman5,8, Paul C Boutros9,10, Andrzej Chruscinski11, Joan Wither1,2,8. 1. Department of Immunology, Faculty of Medicine, University of Toronto. 2. Schroeder Arthritis Institute, Krembil Research Institute, University Health Network. 3. Ontario Institute for Cancer Research. 4. Toronto Scleroderma Program, Division of Rheumatology, Toronto Western and Mount Sinai Hospitals. 5. Department of Medicine, University of Toronto, Faculty of Medicine. 6. University of Toronto Lupus Clinic, Centre for Prognosis Studies in Rheumatic Diseases, Schroeder Arthritis Institute, University Health Network. 7. Division of Rheumatology, Hospital for Sick Children and Department of Paediatrics, University of Toronto. 8. Division of Rheumatology, Schroeder Arthritis Institute, University Health Network, Toronto, ON, Canada. 9. Department of Human Genetics, Institute for Precision Health. 10. Jonsson Comprehensive Cancer Center, Departments of Medicine and Urology, University of California, Los Angeles, Los Angeles, CA, USA. 11. Multi-Organ Transplant Program, University Health Network, Toronto, ON, Canada.
Abstract
OBJECTIVE: We investigated the autoantibody (autoAb) profiles in ANA+ individuals lacking systemic autoimmune rheumatic disease (SARD) and early SARD patients to determine the key differences between these groups and identify factors that are associated with an increased risk of symptomatic progression within the next 2 years in ANA+ individuals. METHODS: Using custom antigen (Ag) microarrays, 144 IgM and IgG autoAbs were surveyed in 84 asymptomatic and 123 symptomatic (48 UCTD and 75 SARD patients) ANA+ individuals. AutoAbs were compared in ANA+ individuals lacking a SARD diagnosis with ≥2 years follow-up (n = 52), including all those who demonstrated progression (n = 14) during this period, with changes over time assessed in a representative subset. RESULTS: We show that ANA+ individuals have autoAb to many self-Ags that are not being captured by current screening techniques and very high levels of these autoAbs are predominantly restricted to early SARD patients, with SLE patients displaying reactivity to many more autoAgs than the other groups. In general, the symptoms that developed in progressors mirrored those seen in SARD patients with similar patterns of autoAbs. Only anti-Ro52 Abs were found to predict progression (positive predictive value 46%, negative predictive value 89%). Surprisingly, over 2 years of follow-up the levels of autoAbs remained remarkably stable regardless of whether individuals progressed or not. CONCLUSION: Our findings strongly argue that development of assays with an expanded set of auto-Ags and enhanced dynamic range would improve the diagnostic and prognostic ability of autoAb testing.
OBJECTIVE: We investigated the autoantibody (autoAb) profiles in ANA+ individuals lacking systemic autoimmune rheumatic disease (SARD) and early SARD patients to determine the key differences between these groups and identify factors that are associated with an increased risk of symptomatic progression within the next 2 years in ANA+ individuals. METHODS: Using custom antigen (Ag) microarrays, 144 IgM and IgG autoAbs were surveyed in 84 asymptomatic and 123 symptomatic (48 UCTD and 75 SARD patients) ANA+ individuals. AutoAbs were compared in ANA+ individuals lacking a SARD diagnosis with ≥2 years follow-up (n = 52), including all those who demonstrated progression (n = 14) during this period, with changes over time assessed in a representative subset. RESULTS: We show that ANA+ individuals have autoAb to many self-Ags that are not being captured by current screening techniques and very high levels of these autoAbs are predominantly restricted to early SARD patients, with SLE patients displaying reactivity to many more autoAgs than the other groups. In general, the symptoms that developed in progressors mirrored those seen in SARD patients with similar patterns of autoAbs. Only anti-Ro52 Abs were found to predict progression (positive predictive value 46%, negative predictive value 89%). Surprisingly, over 2 years of follow-up the levels of autoAbs remained remarkably stable regardless of whether individuals progressed or not. CONCLUSION: Our findings strongly argue that development of assays with an expanded set of auto-Ags and enhanced dynamic range would improve the diagnostic and prognostic ability of autoAb testing.
Authors: Susan M Armstrong; Joan E Wither; Alan M Borowoy; Carolina Landolt-Marticorena; Aileen M Davis; Sindhu R Johnson Journal: J Rheumatol Date: 2016-11-01 Impact factor: 4.666
Authors: Alexander Espinosa; Valerie Dardalhon; Susanna Brauner; Aurelie Ambrosi; Rowan Higgs; Fransisco J Quintana; Maria Sjöstrand; Maija-Leena Eloranta; Joan Ní Gabhann; Ola Winqvist; Birgitta Sundelin; Caroline A Jefferies; Björn Rozell; Vijay K Kuchroo; Marie Wahren-Herlenius Journal: J Exp Med Date: 2009-07-27 Impact factor: 14.307
Authors: Melissa R Arbuckle; Micah T McClain; Mark V Rubertone; R Hal Scofield; Gregory J Dennis; Judith A James; John B Harley Journal: N Engl J Med Date: 2003-10-16 Impact factor: 91.245
Authors: Andrzej Chruscinski; Flora Y Y Huang; Albert Nguyen; Jocelyn Lioe; Laura C Tumiati; Stella Kozuszko; Kathryn J Tinckam; Vivek Rao; Shannon E Dunn; Michael A Persinger; Gary A Levy; Heather J Ross Journal: PLoS One Date: 2016-03-11 Impact factor: 3.240
Authors: Rashi Gupta; Emma Vanlieshout; Kieran Manion; Dennisse Bonilla; Michael Kim; Carolina Muñoz-Grajales; Carol Nassar; Sindhu R Johnson; Linda T Hiraki; Zareen Ahmad; Zahi Touma; Arthur Bookman; Joan E Wither Journal: Front Immunol Date: 2022-06-30 Impact factor: 8.786