Anti-CD19 CAR-T cell therapy in MRL/lpr mice ameliorate established Lupus Nephrites by eliminating CD19+ B-cells as shown by reduced PAX5 transcription factor in BM and spleen. 

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Presentation Time: 02:15 PM - 03:30 PM
Poster Board Number: B610
Abstract ID: 6300

Presenting Author:
Indira Neeli , Research Associate at Univ. of Tennessee Hlth. Sci.Ctr.

Abstract:

SLE is a chronic autoimmune disease that is difficult to diagnose and treat. Our lab demonstrated that anti-CD19 CAR-T cell therapy eliminates CD19+ B cells and improves disease in MRL/lpr mice. Treated mice had undetectable anti-DNA, anti-histone, and anti-cardiolipin autoantibodies, reversed proteinuria, and Lupus Nephrites. Here we analyzed B-cell subpopulations by flow cytometry, quantitative PCR, and measured autoantibody specificities by ELISA, antigen microarrays and ANA both before and after treatment with anti-CD19 CAR-T cells. Our results reveal that autoantibodies to RNP autoantigens persisted in treated mice, indicating that anti-RNP are less effectively regulated by anti-CD19 CAR T cells. The antigen arrays revealed that specific autoantibodies are eliminated but others persist. Flow cytometry analysis of B-cell subpopulations in spleen revealed that the CD19 CAR-T cells eliminate short lived but not long-lived plasma cells.  Our data show a greater than 100-fold decrease in PAX5 and Rag1, which are critical for B cell development, without significant change in Blimp1, suggesting that the CAR-T cells depletes ProB cells prior to Ig gene rearrangement. Thus, our study opens new ways to discover what autoantibodies are tied to prevalent manifestations of lupus and at what stage the CAR-T cells interrupt B-cell development in BM.