Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder in which the immune system attacks healthy tissues, producing symptoms that range from mild to life-threatening. Lupus nephritis (LN), is a severe complication of SLE. It involves kidney inflammation and damage, and a major cause of morbidity in SLE patients. SLE shows a marked sex bias, with up to 90% of adult patients being female. Evidence suggests that this could be due to disrupted gene dosage of X chromosome genes. In healthy females, one copy of the two X-chromosomes undergoes inactivation (XCI), resulting in similar dosage as in males for most X-linked genes. Disruptions to this process, including increased expression of immune-related X-linked genes, have been implicated in lupus.
We have investigated the genetic, transcriptional, and XCI characteristics of peripheral blood immune cells in female LN patients and healthy controls using long-read single-cell RNA sequencing. Preliminary analyses shows that allele specific expression can be used to assign cells into X-chromosomal haplotypes. We identify known and novel X-linked genes which escape X-inactivation through allelic ratios. The approach demonstrates the feasibility of integrating long-read single-cell transcriptomics to explore potential links between X-chromosome dosage regulation and sex-biased susceptibility in autoimmune disease.