GLOBAL IMMUNE REPERTOIRE PROFILING SUGGESTS MULTIFACETED UNRESOLVED DYSREGULATION UPON SYSTEMIC LUPUS ERYTHEMATOSUS IMMUNOSUPPRESSANT THERAPY

PV004 / #575 Poster Topic: AS01 - Adaptive Immunity Background/Purpose Examination of cross-treatment immune dynamics and its potential contribution to the relapse of systemic lupus erythematosus (SLE) in the real clinical setting. Methods We performed single-cell RNA and VDJ profiling on 31 samples from 24 individuals in total, consisting of 20 naïve SLE patients, 7 matched standard-of-care-treated SLE patients, and 4 health control samples. Along with published SLE data, we compiled a comprehensive SLE immune atlas of ~1.6 million cells. Results While the treatment did lead to the suppression of global immune overactivity, we discovered for the first time its failure to effectively restore several undocumented abnormalities in treatment-naïve patients, including the drop in somatic hypermutation (SHM) of memory and DN B cells, and the clonal expansion of CD4 + Th1 and CD8 + memory T cells. Conclusions Our study provides valuable data and sheds lights on the underlying multifaceted unresolved dysregulation upon SLE immunosuppressant therapy under the real clinical setting; such dysregulation may further contribute to the high post-treatment relapse rate and thus call for additional target-specific treatment strategies.