WEHI PhD Completion Seminar hosted by Associate Professor Rhys Allan

Sara Berent
PhD Student – Allan Laboratory, Immunity division, WEHI

Molecular profiling of immune dysregulation in lupus nephritis

Davis Auditorium

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Including Q&A session

Systemic lupus erythematous (SLE) is an autoimmune disease that can impact multiple organ systems, causing significant morbidity and mortality. Lupus nephritis (LN) is one of the most severe forms of SLE, defined by kidney immune infiltration and damage. LN affects predominantly young women and carries a significant risk of organ failure.  Due to the high heterogeneity of disease manifestations, immune mechanisms that drive disease flares and treatment resistance remain poorly understood.

During their PhD Sara has applied long-read single-cell RNA sequencing, urine and plasma protein profiling and flow cytometry to map immune dysregulation across blood and kidney in LN patients. This peripheral immune profiling reveals cell repertoire shifts that mirror disease severity and predict flare. 

In addition to characterising the disease on cellular level, Sara has also explored the molecular underpinnings of LN. Over 90% of LN patients are female, which strongly suggests a sex-specific disease driver. The X chromosome has long been speculated to underlie the striking female predominance of autoimmunity due to possibly increased dosage of gene expression from the inactive X. By analysing X chromosome silencing and escape at single-cell resolution, Sara’s PhD project directly interrogates that hypothesis and detects canonical expression from the inactive X chromosome in both healthy controls and 21 LN patients across varying disease severity, but contradicts the extent and escape status of previously reported genes of interest. Thus, Sara’s findings reframe our understanding of X chromosome biology in autoimmune disease.

All welcome!