自身抗体多样性与层级结构中的种族差异：来自美国系统性硬化症患者队列的更多线索
Ethnic Differences in Autoantibody Diversity and Hierarchy: More Clues from a US Cohort of Patients with Systemic Sclerosis.
作者信息
Nandiwada Sarada L, Peterson Lisa K, Mayes Maureen D, Jaskowski Troy D, Malmberg Elisabeth, Assassi Shervin, Satoh Minoru, Tebo Anne E
机构信息
From 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.
出版信息
J Rheumatol. 2016 Oct;43(10):1816-1824. doi: 10.3899/jrheum.160106. Epub 2016 Aug 1.
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.
目的
确定美国系统性硬化症（SSc）多民族队列中的自身抗体谱及其临床关联。
方法
1000例SSc患者（196例西班牙裔、228例非裔美国人、555例白人及21例其他族裔）接受了抗核抗体（ANA）筛查，包括通过间接免疫荧光法检测抗着丝点抗体（ACA）、通过免疫扩散法检测抗拓扑异构酶-1（topo-1/Scl-70）以及通过酶联免疫吸附测定法检测抗RNA聚合酶III（RNAP III）。对160例主要呈现核仁型和/或斑点型ANA模式，但ACA、Scl-70和RNAP III检测均为阴性的患者血清，通过免疫沉淀法进一步鉴定SSc特异性抗体。
结果
不同种族中抗RNAP III、Th/To和PM/Scl抗体的患病率无显著差异。白人中抗Scl-70的频率最低（18.0%），而西班牙裔和非裔美国人中分别为24.0%和26.8%（p = 0.01）。与非裔美国患者相比，西班牙裔和白人患者的ACA频率更高（p < 0.0001），U3-RNP频率更低（p < 0.0001）。非裔美国患者中U3-RNP抗体独特地更高，与临床亚型无关，而Th/To自身抗体与白人患者的局限性皮肤型SSc相关。总体而言，与白人患者相比，西班牙裔和非裔美国患者发病年龄更早，弥漫性皮肤型SSc更为常见。
结论
SSc特异性抗体可能预测疾病亚型；然而，其患病率在不同种族中的排序有所不同。本研究提供了迄今为止关于自身抗体在西班牙裔美国患者SSc诊断和临床表现中的相关性的最广泛分析。
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