Expression of APOBEC family members as regulators of endogenous retroelements and malignant transformation in systemic autoimmunity

Objective: To explore whether APOBEC family members are involved in the response to inappropriate expression of L1 retroelements in primary Sjogren'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.

Automated summary

The study revealed an important role of APOBEC family members in the pathogenesis of systemic autoimmunity and SS-related lymphomagenesis. APOBEC3A was positively correlated with L1 expression, and AID and APOBEC3G were found to be overexpressed in samples from SS lymphoma patients.