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抗 DFS70 抗体在系统性红斑狼疮中的研究:一项大型中国队列研究的患病率及其与抗 dsDNA 抗体的长期随访中的意外关联。

Anti-DFS70 antibodies in systemic lupus erythematosus: Prevalence in a large Chinese cohort and an unexpected association with anti-dsDNA antibodies by a long-term follow-up.

机构信息

Department of Laboratory Medicine, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Front Immunol. 2022 Sep 14;13:913714. doi: 10.3389/fimmu.2022.913714. eCollection 2022.

DOI:10.3389/fimmu.2022.913714
PMID:36189276
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9515321/
Abstract

OBJECTIVE

Monospecific autoantibodies to dense fine speckles 70 (DFS70) antigen are purported to aid in excluding systemic autoimmune rheumatic diseases (SARD) such as systemic lupus erythematosus (SLE). However, the non-isolated anti-DFS70 still has a certain prevalence in SLE patients, and the clinical significance remains unclear. We aimed to investigate the prevalence, clinical relevance, and value of long-term monitoring of anti-DFS70 antibodies in SLE patients.

METHODS

Anti-DFS70 antibodies were measured by enzyme-linked immunosorbent assay (ELISA) in 851 SLE patients, 211 healthy individuals, and 194 patients with other SARD (except SLE). Demographic, serological, and clinical associations of anti-DFS70 antibodies were analyzed by a stepwise multivariable logistic regression model. The correlation of anti-DFS70 with anti-dsDNA, anti-C1q, and SLE Disease Activity Index 2000 (SLEDAI-2K) was analyzed. Sixty-one SLE patients with follow-up time ranging from 2 to 57 months were measured anti-DFS70 antibodies using both ELISA and line immunoassay. The dynamic variations of anti-DFS70 antibodies were evaluated with anti-dsDNA, anti-C1q, and SLEDAI-2K during the follow-up.

RESULTS

The prevalence of anti-DFS70 was significantly higher in SLE (20.7% (176/851)) than in healthy individuals (9.5% (20/211), = 0.0002) and other SARD (10.8% (21/194), = 0.002). Multivariable analysis revealed that anti-DFS70-positive SLE patients were associated with younger age (odds ratio (OR) = 0.982; 95% confidence interval (CI) = 0.969, 0.995), higher frequencies of anti-dsDNA (OR 1.598; 95% CI 1.107, 2.306) and anti-PCNA (OR 6.101; 95% CI 2.534, 14.688), and higher levels of serum IgG (OR 1.097; 95% CI 1.067, 1.129) and were more likely to be accompanied by mucosal ulcers (OR 5.921; 95% CI 1.652, 21.215). The O.D. value of anti-DFS70 positively correlated with levels of anti-dsDNA ( = 0.183, < 0.0001) and anti-C1q ( = 0.181, < 0.0001), respectively, but not with SLEDAI-2K ( = 0.920). During the follow-up, 49 (42 negative and 7 positive) patients remained stable with anti-DFS70 levels. The other 12 patients experienced significant changes in anti-DFS70, and 83.3% (10/12) of them showed similar trends between anti-DFS70 and anti-dsDNA by evaluation of dynamic variations.

CONCLUSION

Anti-DFS70 antibodies seem to be prevalent in Chinese SLE patients. The positive association of anti-DFS70 with anti-dsDNA and consistent dynamic variation between anti-DFS70 and anti-dsDNA during the follow-up suggested a potential relationship between anti-DFS70 and anti-dsDNA in patients with SLE.

摘要

目的

针对致密细斑点 70(DFS70)抗原的单特异性自身抗体被认为有助于排除系统性自身免疫性风湿病(SARD),如系统性红斑狼疮(SLE)。然而,非分离的抗-DFS70在 SLE 患者中仍有一定的流行率,其临床意义尚不清楚。我们旨在研究 SLE 患者抗-DFS70 抗体的流行率、临床相关性和长期监测价值。

方法

采用酶联免疫吸附试验(ELISA)检测 851 例 SLE 患者、211 例健康对照者和 194 例其他 SARD(除外 SLE)患者的抗-DFS70 抗体。采用逐步多变量逻辑回归模型分析抗-DFS70 抗体与人口统计学、血清学和临床的相关性。分析抗-DFS70 与抗 dsDNA、抗 C1q 和系统性红斑狼疮疾病活动指数 2000(SLEDAI-2K)的相关性。对 61 例随访时间为 2 至 57 个月的 SLE 患者同时采用 ELISA 和线免疫分析法检测抗-DFS70 抗体。在随访期间,评估抗-DFS70 抗体与抗 dsDNA、抗 C1q 和 SLEDAI-2K 的动态变化。

结果

SLE 患者抗-DFS70 的阳性率明显高于健康对照者(20.7%(176/851)比 9.5%(20/211), = 0.0002)和其他 SARD(10.8%(21/194), = 0.002)。多变量分析显示,抗-DFS70 阳性的 SLE 患者与年龄较小(比值比(OR)=0.982;95%置信区间(CI)=0.969,0.995)、抗 dsDNA (OR 1.598;95% CI 1.107,2.306)和抗 PCNA(OR 6.101;95% CI 2.534,14.688)频率较高、血清 IgG 水平较高(OR 1.097;95% CI 1.067,1.129)以及黏膜溃疡更常见(OR 5.921;95% CI 1.652,21.215)有关。抗-DFS70 的 O.D. 值与抗 dsDNA( = 0.183, <0.0001)和抗 C1q( = 0.181, <0.0001)水平呈正相关,而与 SLEDAI-2K ( = 0.920)无相关性。在随访期间,49 例(42 例阴性和 7 例阳性)患者的抗-DFS70 水平保持稳定。其余 12 例患者的抗-DFS70 发生了显著变化,通过评估动态变化,其中 83.3%(10/12)的患者抗-DFS70 和抗 dsDNA 之间表现出相似的趋势。

结论

抗-DFS70 抗体似乎在我国 SLE 患者中普遍存在。抗-DFS70 与抗 dsDNA 的阳性关联以及在随访期间抗-DFS70 与抗 dsDNA 之间一致的动态变化提示在 SLE 患者中抗-DFS70 与抗 dsDNA 之间可能存在一定的关系。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4307/9515321/48cdc0711863/fimmu-13-913714-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4307/9515321/686f22c11fbe/fimmu-13-913714-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4307/9515321/df91e07b1b88/fimmu-13-913714-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4307/9515321/99bbdc9fd931/fimmu-13-913714-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4307/9515321/48cdc0711863/fimmu-13-913714-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4307/9515321/686f22c11fbe/fimmu-13-913714-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4307/9515321/df91e07b1b88/fimmu-13-913714-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4307/9515321/99bbdc9fd931/fimmu-13-913714-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4307/9515321/48cdc0711863/fimmu-13-913714-g004.jpg

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Front Immunol. 2022 Feb 3;13:810639. doi: 10.3389/fimmu.2022.810639. eCollection 2022.
2
Autoantibodies to dense-fine-speckled 70 (DFS70) do not necessarily rule out connective tissue diseases.抗致密斑点 70 抗体(DFS70)并不能排除结缔组织病。
Semin Arthritis Rheum. 2022 Feb;52:151936. doi: 10.1016/j.semarthrit.2021.12.006. Epub 2021 Dec 30.
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Prevalence of anti-dense fine speckled 70 antibodies in healthy individuals and patients with antinuclear antibody-associated autoimmune rheumatic diseases in Japan.
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Medicine (Baltimore). 2021 Mar 5;100(9):e24556. doi: 10.1097/MD.0000000000024556.
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