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Expression of APOBEC family members as regulators of endogenous retroelements and malignant transformation in systemic autoimmunity
Clinical Immunology ( IF 8.6 ) Pub Date : 2020-12-14 , DOI: 10.1016/j.clim.2020.108649
Clio P. Mavragani , Kyriakos A. Kirou , Adrianos Nezos , Surya Seshan , Teresa Wild , Sharon M. Wahl , Haralampos M. Moutsopoulos , Mary K. Crow

Objective

To explore whether APOBEC family members are involved in the response to inappropriate expression of L1 retroelements in primary Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE), as well as in SS related lymphomagenesis.

Methods

Minor salivary glands (MSG) and kidney biopsy (KB) specimens were obtained from 41 SS patients (10 with lymphoma) and 23 patients with SLE, respectively. PBMC and sera were also collected from 73 SLE patients. Full-length L1 transcripts, members of the APOBEC and IFN family were quantitated by real time PCR. Type I IFN activity was assessed in lupus plasma by a cell assay.

Results

APOBEC3A was increased in SS MSG, SLE KB and PBMC and correlated with L1. AID and APOBEC3G were particularly overexpressed in MSG tissues derived from SS lymphoma patients.

Conclusion

These data reveal a previously unappreciated role of APOBEC family proteins in the pathogenesis of systemic autoimmunity and SS related lymphomagenesis.



中文翻译:

APOBEC家族成员在系统性自身免疫中作为内源性逆转录和恶性转化调控因子的表达

目的

探讨APOBEC家族成员是否参与对原发性干燥综合征(SS)和系统性红斑狼疮(SLE)以及SS相关淋巴瘤的L1逆转录表达的不当响应。

方法

分别从41例SS患者(10例淋巴瘤)和23例SLE患者中获得了小唾液腺(MSG)和肾脏活检(KB)标本。还从73例SLE患者中收集了PBMC和血清。全长L1转录本,APOBEC和IFN家族成员通过实时PCR定量。通过细胞测定评估狼疮血浆中的I型IFN活性。

结果

SS MSG,SLE KB和PBMC中APOBEC3A升高,并与L1相关。AID和APOBEC3G在来自SS淋巴瘤患者的MSG组织中特别过表达。

结论

这些数据揭示了APOBEC家族蛋白在全身性自身免疫和SS相关淋巴瘤的发病机理中的作用。

更新日期:2020-12-25
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