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低密粒细胞与系统性红斑狼疮患者妊娠时间缩短有关,但与干扰素-α蛋白血药浓度无关。

Low-density granulocytes are related to shorter pregnancy duration but not to interferon alpha protein blood levels in systemic lupus erythematosus.

机构信息

Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg, Guldhedsgatan 10A, Gothenburg, 405 30, Sweden.

Rheumatology, Sahlgrenska University Hospital, Gothenburg, Sweden.

出版信息

Arthritis Res Ther. 2023 Jun 22;25(1):107. doi: 10.1186/s13075-023-03092-w.

Abstract

BACKGROUND

An increased risk of pregnancy complications is seen in women with systemic lupus erythematosus (SLE), but the specific immunopathological drivers are still unclear. Hallmarks of SLE are granulocyte activation, type I interferon (IFN) overproduction, and autoantibodies. Here we examined whether low-density granulocytes (LDG) and granulocyte activation increase during pregnancy, and related the results to IFNα protein levels, autoantibody profile, and gestational age at birth.

METHODS

Repeated blood samples were collected during pregnancy in trimesters one, two, and three from 69 women with SLE and 27 healthy pregnant women (HC). Nineteen of the SLE women were also sampled late postpartum. LDG proportions and granulocyte activation (CD62L shedding) were measured by flow cytometry. Plasma IFNα protein concentrations were quantified by single molecule array (Simoa) immune assay. Clinical data were obtained from medical records.

RESULTS

Women with SLE had higher LDG proportions and increased IFNα protein levels compared to HC throughout pregnancy, but neither LDG fractions nor IFNα levels differed during pregnancy compared to postpartum in SLE. Granulocyte activation status was higher in SLE relative to HC pregnancies, and it was increased during pregnancy compared to after pregnancy in SLE. Higher LDG proportions in SLE were associated with antiphospholipid positivity but not to IFNα protein levels. Finally, higher LDG proportions in trimester three correlated independently with lower gestational age at birth in SLE.

CONCLUSION

Our results suggest that SLE pregnancy results in increased peripheral granulocyte priming, and that higher LDG proportions late in pregnancy are related to shorter pregnancy duration but not to IFNα blood levels in SLE.

摘要

背景

系统性红斑狼疮(SLE)患者妊娠并发症的风险增加,但具体的免疫病理驱动因素仍不清楚。SLE 的特征是粒细胞激活、I 型干扰素(IFN)过度产生和自身抗体。在这里,我们检查了低密粒细胞(LDG)和粒细胞激活是否在妊娠期间增加,并将结果与 IFNα 蛋白水平、自身抗体谱和出生时的孕龄相关联。

方法

从 SLE 患者的妊娠第一、二、三期和 27 名健康孕妇(HC)中重复采集 69 名 SLE 患者和 27 名健康孕妇(HC)的血液样本。19 名 SLE 妇女也在产后晚期采样。通过流式细胞术测量 LDG 比例和粒细胞激活(CD62L 脱落)。通过单分子阵列(Simoa)免疫分析定量测定血浆 IFNα 蛋白浓度。临床数据从病历中获得。

结果

与 HC 相比,SLE 患者在整个孕期的 LDG 比例较高,IFNα 蛋白水平较高,但与产后相比,SLE 患者在孕期和产后期间的 LDG 分数和 IFNα 水平均无差异。与 HC 妊娠相比,SLE 患者的粒细胞激活状态较高,与产后相比,SLE 患者在妊娠期间的粒细胞激活状态较高。SLE 患者的 LDG 比例较高与抗磷脂阳性有关,但与 IFNα 蛋白水平无关。最后,SLE 患者妊娠晚期 LDG 比例较高与出生时的孕龄较短独立相关。

结论

我们的研究结果表明,SLE 妊娠导致外周粒细胞的初始激活增加,妊娠晚期 LDG 比例较高与妊娠持续时间较短有关,但与 SLE 患者的 IFNα 血液水平无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d170/10286457/12175429fd71/13075_2023_3092_Fig1_HTML.jpg

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