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
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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)