Anti-DFS70 Antibodies Among Patient and Healthy Population Cohorts in China: Results From a Multicenter Training Program Showing Spontaneous Abortion and Pediatric Systemic Autoimmune Rheumatic Diseases Are Common in Anti-DFS70 Positive Patients.

Bing Zheng,Lin Yuan,Dengtao Liu,Huiyuan Liu,Shanshan Han,Shishi Chen,Lijun Wu,Shuimian Chen,Zhen Li,Zhenzhen Niu,Jing Liu,Li Chen,Huiyun Gong,Edward K L Chan,Xiaoying Guo,Fuying Zhai,Meng Hao,Chihui Li,Shunfei Zhu,Loujian Jie,Zhiqing Wang,Yan Wang,Ping Xu,Weihua Sun,Lina Ying,Yajuan Chen,Aiping Liu,Qimiao Lu ,Meian He ,Rodrigo Mora ,Ye-Min Qu ,Zhonglin Han ,Jia Zhou

doi:10.3389/fimmu.2020.562138

Abstract

ObjectiveAnti-DFS70 antibodies correlating with the nuclear dense fine speckled (DFS) pattern in the HEp-2 indirect immunofluorescence assay (IFA) are less common in patients with systemic autoimmune rheumatic disease (SARD) than in healthy subjects and their clinical associations remain elusive. We hosted a multi-center HEp-2 IFA training program to improve the ability of clinical laboratories to recognize the DFS pattern and to investigate the prevalence and relevance of anti-DFS70 antibodies.MethodsDFS pattern sera identified by HEp-2 IFA in 29 centers in China were redirected to a central laboratory for anti-DFS70 testing by line immunoblot assay (LIA), enzyme-linked immunosorbent assay (ELISA), and IFA with HEp-2 ELITE/DFS70-KO substrate. Anti-extractable nuclear antigen antibodies were measured by LIA and the clinical relevance was examined in adult and pediatric patients.ResultsHEp-2 IFA positive rate and DFS pattern in positive sera were 36.2% (34,417/95,131) and 1.7% (582/34,417) in the patient cohort, and 10.0% (423/4,234) and 7.8% (33/423) in a healthy population, respectively. Anti-DFS70 prevalence among sera presenting the DFS pattern was 96.0, 93.7, and 49.6% by ELISA, LIA, and HEp-2 ELITE, respectively. 15.5% (52/336) of adult and 50.0% (20/40) of pediatric anti-DFS70 positive patients were diagnosed with SARD. Diseases most common in anti-DFS70 positive patients were spontaneous abortion (28.0%) in adults and juvenile idiopathic arthritis (22.5%) in pediatric patients.ConclusionAccurate DFS pattern identification increased the detection rate of anti-DFS70 antibodies by ELISA and LIA. Anti-DFS70 antibodies are remarkably high in cases of spontaneous abortion and in pediatric SARD patients, but not prevalent in adult SARD patients.

Highlights

Antinuclear antibodies (ANA) are commonly regarded as serological hallmarks of systemic autoimmune rheumatic disease (SARD) [1]
The presence of isolated anti-dense fine speckled 70 kDa antigen (DFS70) antibodies has been proposed to serve as a diagnostic biomarker to help rule out SARD [4, 15, 16], which highlights the importance of correctly identifying these antibodies in clinical laboratories
Correlations between the anti-DFS70 antibodies detected by specific assays and the DFS pattern have been reported higher than 90% [19]

Summary

Introduction

Antinuclear antibodies (ANA) are commonly regarded as serological hallmarks of systemic autoimmune rheumatic disease (SARD) [1]. Many studies have focused on the clinical relevance of anti-DFS70 antibodies [reviewed in [5]] and their prevalence has been reported in some chronic inflammatory diseases [2, 11, 12] and cancers [e.g. prostate cancer [13, 14]], but still no clear. Correlations between the anti-DFS70 antibodies detected by specific assays and the DFS pattern have been reported higher than 90% [19]. Further efforts still need to be placed on training to recognize the DFS pattern

Methods

Results

Conclusion