去唾液酸化和唾液酸化的 IgG 抗 dsDNA 抗体分别加重和减轻实验性小鼠狼疮蛋白尿及其可能机制。

De-sialylated and sialylated IgG anti-dsDNA antibodies respectively worsen and mitigate experimental mouse lupus proteinuria and possible mechanisms.

机构信息

Division of Rheumatology, Allergy, and Immunology, New Taipei Municipal Tucheng Hospital, New Taipei City, Taiwan; Division of Rheumatology, Allergy, and Immunology, Chang Gung Memorial Hospital at Linkou, Tao-yuan, Taiwan; Division of Rheumatology, Allergy, and Immunology, Chang Gung Memorial Hospital at Keelung, Keelung, Taiwan; School of Medicine, Chang Gung University College of Medicine, Tao-yuan, Taiwan.

出版信息

Int Immunopharmacol. 2022 Aug;109:108837. doi: 10.1016/j.intimp.2022.108837. Epub 2022 May 28.

DOI:10.1016/j.intimp.2022.108837

PMID:35640407

Abstract

BACKGROUND

The role of sialylated and de-sialylated (de-SIA) IgG anti-dsDNA antibodies in experimental mouse lupus remains unclear.

AIM OF THE STUDY

To examine how sialylated and de-SIA IgG anti-dsDNA antibodies affect lupus mouse proteinuria and possible mechanisms.

METHODS

Blood was serially obtained from pristane-induced female BALB/c lupus mice to assess correlations between alpha-2,6-sialic cid (SIA) ratios of serum IgG anti-dsDNA and proteinuria. Kidney C3 staining was correlated with blood IgG anti-dsDNA. Sialylated IgG anti-dsDNA with its de-SIA form was administered to determine the effect on lupus proteinuria and in vitro consequences.

RESULTS

We observed that the SIA contents of IgG anti-dsDNA were lower in Week 16/1+ (Week 16 with 1 + proteinuria) and W24/2 + mice than those in W16 (no proteinuria) and W24/1 + mice, respectively (P < 0.005 for both). C3 staining densities in the kidney correlated inversely with the α-2,6-SIA content of plasma IgG anti-dsDNA (r = -0.660). Highly sialylated A52L1 IgG anti-dsDNA injection mitigated lupus proteinuria significantly from PBS injection; however, its de-SIA form worsened proteinuria (aggravation of proteinuria: the latter vs. the former [sialylated A52L1 IgG anti-dsDNA] with an infinite odds ratio). Highly sialylated A52L1 IgG anti-dsDNA resulted in higher interleukin (IL)-10/IL-12 ratios, higher transforming growth factor-β1 levels, and lower tumor necrosis factor-α levels in sera than its de-SIA from.

CONCLUSION

We concluded that a low SIA/serum IgG anti-dsDNA ratio indicated a high severity of nephritis in pristane-induced lupus mice. Highly sialylated IgG anti-dsDNA, in contrast to the de-SIA form, alleviated the severity of lupus proteinuria.

摘要

背景

唾液酸化和去唾液酸化（去 SIA）IgG 抗 dsDNA 抗体在实验性狼疮小鼠中的作用尚不清楚。

目的

研究唾液酸化和去 SIA IgG 抗 dsDNA 抗体如何影响狼疮小鼠蛋白尿及其可能的机制。

方法

从 pristane 诱导的雌性 BALB/c 狼疮小鼠中连续采集血液，以评估血清 IgG 抗 dsDNA 的α-2,6-唾液酸（SIA）比值与蛋白尿之间的相关性。将肾脏 C3 染色与血液 IgG 抗 dsDNA 相关联。给予唾液酸化 IgG 抗 dsDNA 及其去 SIA 形式，以确定其对狼疮蛋白尿的影响及其体外后果。

结果

我们观察到，在第 16 周/1+（第 16 周有 1+蛋白尿）和第 24 周/2+小鼠中，IgG 抗 dsDNA 的 SIA 含量低于第 16 周（无蛋白尿）和第 24 周/1+小鼠（均 P<0.005）。肾脏 C3 染色密度与血浆 IgG 抗 dsDNA 的α-2,6-SIA 含量呈负相关（r=-0.660）。高唾液酸化 A52L1 IgG 抗 dsDNA 显著减轻 PBS 注射引起的狼疮蛋白尿；然而，其去 SIA 形式加重蛋白尿（蛋白尿加重：后者与前者[高唾液酸化 A52L1 IgG 抗 dsDNA]呈无限比值比）。高唾液酸化 A52L1 IgG 抗 dsDNA 导致血清中白细胞介素（IL）-10/IL-12 比值升高、转化生长因子-β1 水平升高和肿瘤坏死因子-α水平降低，而其去 SIA 形式则相反。