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非肥胖糖尿病(NOD)小鼠和正常(NOR)小鼠的血清及泪液自身抗体作为干燥综合征局部和全身炎症的潜在诊断指标

Serum and Tear Autoantibodies from NOD and NOR Mice as Potential Diagnostic Indicators of Local and Systemic Inflammation in Sjögren's Disease.

作者信息

Kakan Shruti Singh, Abdelhamid Sara, Ju Yaping, MacKay J Andrew, Edman Maria C, Raman Indu, Zhu Chengsong, Raj Prithvi, Hamm-Alvarez Sarah F

出版信息

bioRxiv. 2024 Oct 29:2024.10.24.619993. doi: 10.1101/2024.10.24.619993.

Abstract

BACKGROUND

Sjögren's Disease (SjD) is an autoimmune disease characterized by lymphocytic infiltration of salivary and lacrimal glands (LG). The LG produces the protein-rich aqueous component of tears, and SjD-associated autoimmune dacryoadenitis (AD) may thus alter tear autoantibody composition.

METHODS

The presence of tertiary lymphoid structures (TLS) in LG from two murine models of SjD-associated AD, male NOD and male NOR mice, were evaluated using immunofluorescence. IgG and IgA reactivity in serum and tears from these models were probed in three studies against a panel of 80-120 autoantigens using autoantibody microarrays relative to serum and tears from healthy male BALB/c mice. Data were analyzed by R package Limma.

RESULTS

Analysis of immunofluorescence in LG sections from both SjD models showed TLS. Only one autoantibody was significantly elevated in tears and serum in both SjD models across all studies. Three autoantibodies were significantly elevated in serum but not in tears in both SjD models across all studies. Conversely, six IgG and thirteen IgA autoantibodies (6 sharing the same autoantigen) were significantly elevated in tears but not serum in both SjD models.

CONCLUSION

NOD and NOR mice with SjD-associated AD have distinct autoantibody profiles in tears and serum. Tear IgA isotype autoantibodies showed a greater diversity than tear IgG autoantibodies. TLS observed in LG are a likely source of the tear autoantibodies.

摘要

背景

干燥综合征(SjD)是一种自身免疫性疾病,其特征是唾液腺和泪腺(LG)出现淋巴细胞浸润。泪腺产生富含蛋白质的泪液水性成分,因此与SjD相关的自身免疫性泪腺炎(AD)可能会改变泪液自身抗体的组成。

方法

使用免疫荧光评估来自两种与SjD相关的AD小鼠模型(雄性非肥胖糖尿病(NOD)小鼠和雄性挪威(NOR)小鼠)的泪腺中三级淋巴结构(TLS)的存在情况。在三项研究中,使用自身抗体微阵列,针对一组80 - 120种自身抗原,检测这些模型血清和泪液中的IgG和IgA反应性,并与健康雄性BALB/c小鼠的血清和泪液进行比较。数据通过R包Limma进行分析。

结果

对两种SjD模型的泪腺切片进行免疫荧光分析显示存在TLS。在所有研究中,两种SjD模型的泪液和血清中只有一种自身抗体显著升高。在所有研究中,两种SjD模型的血清中有三种自身抗体显著升高,但泪液中未升高。相反,在两种SjD模型中,六种IgG自身抗体和十三种IgA自身抗体(其中6种共享相同的自身抗原)在泪液中显著升高,但血清中未升高。

结论

患有与SjD相关的AD的NOD和NOR小鼠在泪液和血清中具有不同的自身抗体谱。泪液IgA同种型自身抗体显示出比泪液IgG自身抗体更大的多样性。在泪腺中观察到的TLS可能是泪液自身抗体的来源。

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