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BAFF 抑制和 B 细胞耗竭在非肥胖型糖尿病小鼠中的疗效，作为干燥综合征的自发性模型。

Efficacy of BAFF inhibition and B-cell depletion in non-obese diabetic mice as a spontaneous model for Sjögren's disease.

机构信息

Service de Rhumatologie - Centre National de Référence des maladies auto-immuneset et auto-inflammatoires systémiques rares RESO, Hopitaux universitaires de Strasbourg, Strasbourg, France.

Immunologie, Immunopathologie et Chimie Thérapeutique, CNRS UPR 3572, IBMC, Strasbourg, France.

出版信息

RMD Open. 2024 Aug 28;10(3):e004112. doi: 10.1136/rmdopen-2024-004112.

DOI:10.1136/rmdopen-2024-004112
PMID:39209370
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11367362/
Abstract

INTRODUCTION

The therapeutic interest of targeting B-cell activating factor (BAFF) in Sjögren's disease (SjD) can be suspected from the results of two phase II clinical trials but has not been evaluated in an animal model of the disease. We aimed to evaluate the therapeutic efficacy of this strategy on dryness and salivary gland (SG) infiltrates in the NOD mouse model of SjD.

MATERIAL AND METHODS

Female NOD mice between ages 10 and 18 weeks were treated with a BAFF-blocking monoclonal antibody, Sandy-2 or an isotype control. Dryness was measured by the stimulated salivary flow. Salivary lymphocytic infiltrates were assessed by immunohistochemistry. Blood, SGs, spleen and lymph-node lymphocyte subpopulations were analysed by flow cytometry. SG mRNA expression was analysed by transcriptomic analysis.

RESULTS

BAFF inhibition significantly decreased SG lymphocytic infiltrates, which was inversely correlated with salivary flow. The treatment markedly decreased B-cell number in SGs, blood, lymph nodes and spleen and increased Foxp3 regulatory and CD3CD4CD8 double negative T-cell numbers in SGs.

CONCLUSION

A monoclonal antibody blocking BAFF and depleting B cells had therapeutic effectiveness in the NOD mouse model of SjD. The increase in regulatory T-lymphocyte populations might underlie the efficacy of this treatment.

摘要

简介

从两项 II 期临床试验的结果可以推测出靶向 B 细胞激活因子（BAFF）在干燥综合征（SjD）中的治疗意义，但尚未在疾病的动物模型中进行评估。我们旨在评估该策略对 NOD 小鼠 SjD 模型中干燥和唾液腺（SG）浸润的治疗效果。

材料和方法

年龄在 10 至 18 周之间的雌性 NOD 小鼠接受 BAFF 阻断单克隆抗体 Sandy-2 或同型对照治疗。通过刺激唾液流来测量干燥度。通过免疫组织化学评估唾液淋巴细胞浸润。通过流式细胞术分析血液、SG、脾脏和淋巴结淋巴细胞亚群。通过转录组分析分析 SG mRNA 表达。

结果

BAFF 抑制显著减少了 SG 淋巴细胞浸润，这与唾液流量呈负相关。该治疗显著减少了 SG、血液、淋巴结和脾脏中的 B 细胞数量，并增加了 SG 中的 Foxp3 调节性和 CD3CD4CD8 双阴性 T 细胞数量。

结论

阻断 BAFF 并耗尽 B 细胞的单克隆抗体在 SjD 的 NOD 小鼠模型中具有治疗效果。调节性 T 淋巴细胞群体的增加可能是这种治疗效果的基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e077/11367362/06ac4e3c6be5/rmdopen-10-3-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e077/11367362/6f25b55e4165/rmdopen-10-3-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e077/11367362/31dc55dea977/rmdopen-10-3-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e077/11367362/8fe7bf1b679e/rmdopen-10-3-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e077/11367362/06ac4e3c6be5/rmdopen-10-3-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e077/11367362/6f25b55e4165/rmdopen-10-3-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e077/11367362/31dc55dea977/rmdopen-10-3-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e077/11367362/8fe7bf1b679e/rmdopen-10-3-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e077/11367362/06ac4e3c6be5/rmdopen-10-3-g004.jpg

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