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Ethnic Differences in Autoantibody Diversity and Hierarchy: More Clues from a US Cohort of Patients with Systemic
Sarada L Nandiwada1, Lisa K Peterson2, Maureen D Mayes2
1From the Department of Pathology, University of Utah; ARUP Laboratories, Salt Lake City, Utah; Section of Allergy, Immunology and Rheumatology, Baylor College of Medicine; Department of Internal Medicine, Division of Rheumatology and Clinical Immunogenetics, University of Texas Health Science Center, Houston, Texas; Department of Medicine, University of Florida, Gainesville, Florida, USA; Department of Clinical Nursing, School of Health Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan.S.L. Nandiwada, PhD, Assistant Professor of Pediatrics, Department of Pathology, University of Utah, and Section of Allergy, Immunology and Rheumatology, Baylor College of Medicine; L.K. Peterson, PhD, Clinical Immunology Fellow, Department of Pathology, University of Utah; M.D. Mayes, MD, Professor of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, Division of Rheumatology and Clinical Immunogenetics, University of Texas Health Science Center; T.D. Jaskowski, BS, R&D Scientist, ARUP Laboratories; E. Malmberg, MS, Outcomes Analyst, ARUP Laboratories; S. Assassi, MD, Associate Professor of Rheumatology and Clinical Immunogenetics, Department of Internal Medicine, Division of Rheumatology and Clinical Immunogenetics, University of Texas Health Science Center; M. Satoh, MD, PhD, Professor, Department of Clinical Nursing, Department of Clinical Nursing, School of Health Sciences, University of Occupational and Environmental Health, and Department of Medicine, University of Florida; A.E. Tebo, PhD, Associate Professor of Pathology, Department of Pathology, University of Utah, and ARUP Laboratories. Dr. Nandiwada and Dr. Peterson contributed equally to this manuscript. anne.tebo@hsc.utah.edu.
Objective:
To determine the autoantibody repertoire and clinical associations in a multiethnic cohort of American patients with systemic sclerosis (SSc).
Methods:
There were 1000 patients with SSc (196 Hispanic, 228 African American, 555 white, and 21 other) who were screened for antinuclear antibodies (ANA), including anticentromere antibodies (ACA) by indirect immunofluorescence assay, antitopoisomerase-1 (topo-1/Scl-70) by immunodiffusion, and anti-RNA polymerase III (RNAP III) by ELISA. Sera from 160 patients with mainly nucleolar and/or speckled ANA pattern, but negative for ACA, Scl-70, and RNAP III, were further characterized by immunoprecipitation for SSc-specific antibodies.
Results:
The prevalence of antibodies against RNAP III, Th/To, and PM/Scl did not differ significantly among the ethnic groups. The frequency of anti-Scl-70 was lowest in whites (18.0%) compared with 24.0% and 26.8% in Hispanics and African Americans (p = 0.01), respectively. Compared with African American patients, Hispanic and white subjects had a higher frequency of ACA (p < 0.0001) and lower frequency of U3-RNP (p < 0.0001). U3-RNP antibodies were uniquely higher in African American patients, independent of clinical subset, while Th/To autoantibodies were associated with limited cutaneous SSc in white subjects. Overall, Hispanic and African American patients had an earlier age of onset and a predominance of diffuse cutaneous SSc compared with their white counterparts.
Conclusion:
SSc-specific antibodies may predict disease subset; however, the hierarchy of their prevalence differs across ethnic groups. This study provides the most extensive analysis to date on the relevance of autoantibodies in the diagnosis and clinical manifestations of SSc in Hispanic American patients.