Establishing a reference interval for serum anti-dsDNA antibody: A large Chinese Han population-based multi-center study

PLOS ONE, Dec 2019

Background A reference interval (RI) for the circulating concentration of anti-dsDNA antibody is essential for clinicians to interpret laboratory results and make clinical decisions. Therefore, we aimed to establish the RI for anti-dsDNA antibody in the Chinese Han population. Methods This study was designed and carried out in accordance with guideline C28-A3, which is proposed by the International Federation of Clinical Chemistry and the Clinical and Laboratory Standards Institute. A total of 2,880 apparently healthy individuals were enrolled using a posteriori sampling. These individuals were recruited from four hospitals, representing the Han populations of north, south, east, and west China. Serum anti-dsDNA antibody levels were measured using the three analytical systems AESKU, EUROIMMUNE, and INOVA, which are the most commonly used systems in China. Individuals were stratified by gender, age, and region, and the RIs were obtained by nonparametric methods. Results Gender-specific RIs for serum anti-dsDNA antibody in the Chinese Han population were established. Conclusion This is the first exploration of the RI for anti-dsDNA antibody in the Chinese Han population. We have established gender-specific RIs for each assay method commonly used in China.

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Establishing a reference interval for serum anti-dsDNA antibody: A large Chinese Han population-based multi-center study

February Establishing a reference interval for serum anti-dsDNA antibody: A large Chinese Han population-based multi-center study Chuiwen Deng 0 1 2 Shulan Zhang 0 1 2 Chaojun Hu 0 1 2 Ping Li 0 1 2 Ziyan Wu 0 1 2 Si Chen 0 1 2 Jing Li 0 1 2 Liubing Li 0 1 2 Fengchun Zhang 0 1 2 Yongzhe Li 0 1 2 0 Funding: This study was supported by the Research Special Fund for Public Welfare Industry of Health , No. 201202004 1 Editor: Xu-jie Zhou, Peking University First Hospital , CHINA 2 Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College , Beijing , China , 2 Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education , Beijing , China - OPEN ACCESS Competing Interests: The authors have declared that no competing interests exist. Background Methods Results established. Conclusion This is the first exploration of the RI for anti-dsDNA antibody in the Chinese Han population. We have established gender-specific RIs for each assay method commonly used in China. Introduction In laboratory medicine, reference intervals (RIs) represent the typical fluctuations in the quantity or quality of body fluid analytes in a relatively healthy population. The concept of an RI was first proposed by Grasbeck et al. in 1968 [ 1 ], and it was initially called a ªnormal valueº. Later, it was realized that the term ªnormalº was scientifically flawed. Then, well-defined nomenclatures, including ªreference value,º ªreference range,º and ªnormal reference rangeº came into use. From a statistical standpoint, the term ªreference intervalº better fits the concept. Sometimes, an RI is confused with a clinical decision limit (CDL). A CDL is the threshold concentration of a body fluid analyte, and a specific medical decision is made when the concentration of an analyte for a given individual is above or below the CDL. Unlike an RI, a CDL is obtained from clinical studies that explore the diagnosis or specific outcome of a certain disease [ 2 ]. Generally, the manufacturers of diagnostic kits are obliged to provide the appropriate RI for clinical laboratories. In diagnostic kits for autoantibodies, most manufacturers provide cutoff values, which are used as RIs. However, not all RIs are rigorously calculated. One of the major issues in the application of RIs has been the lack of standardization in the selection of reference subjects. To address this problem, a standard protocol for establishing an RI (C28-A3) has been proposed by the International Federation of Clinical Chemistry together with the Clinical and Laboratory Standards Institute [ 3 ], and this has been widely used. In addition, the RIs provided with kits are typically calculated using reference subjects from the manufacturer's country or region, and they are not necessarily applicable to individuals in other countries or regions. In China, most of the kits for autoantibody detection, which are procured from outside China, do not provide RIs based on Chinese or Asian populations, resulting in difficulties when evaluating RIs in clinical laboratories. Fifty years ago, researchers found that circulating anti-dsDNA antibodies were present in patients with systemic lupus erythematosus (SLE) [ 4 ]. Subsequently, anti-dsDNA antibodies were shown to play important roles in SLE, both in its pathogenesis and as a biomarker for diagnosis and prognosis [ 5 ]. Thus, anti-dsDNA antibodies were introduced as a diagnostic biomarker in the classification and/or diagnostic criteria for SLE in 1982, 1997, and 2011 [ 6 ]. Then, a proposal was made that the criterion for the inclusion of anti-dsDNA antibody in the classification of SLE should be modified. It was suggested that the anti-dsDNA antibody level should be above the laboratory RI or twice the RI when tested by enzyme-linked immunosorbent assay [ 7 ]. Thus, calculating an accurate RI for the anti-dsDNA antibody level is important for making clinical decisions in SLE. Notably, there is a high incidence of SLE in China [ 8, 9 ], which makes it even more important to define an accurate RI for anti-dsDNA antibody in China. To our knowledge, no study has explored the RI for anti-dsDNA antibody testing in a Chinese population. In the present study, we aimed to recruit a large number of apparently healthy Chinese Han individuals and establish RIs for anti-dsDNA antibody according to the standardized protocol. Methods Selection of reference subjects Since the characteristics of autoantibodies have been poorly studied, and the current literature contains little relevant information, the factors that influence autoantibodies are little known. Based on this background, we chose a posteriori sampling, which was recommended by 2 / 9 C28-A3 and fits the goal of our research. A posteriori sampling proceeds with the exclusion and partitioning of participants after sampling and analyte testing. Reference (...truncated)


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Chuiwen Deng, Shulan Zhang, Chaojun Hu, Ping Li, Ziyan Wu, Si Chen, Jing Li, Liubing Li, Fengchun Zhang, Yongzhe Li. Establishing a reference interval for serum anti-dsDNA antibody: A large Chinese Han population-based multi-center study, PLOS ONE, 2017, Volume 12, Issue 2, DOI: 10.1371/journal.pone.0168871