Early Life Stress in Summer Months Accelerates the Progression of Autoimmunity in Female Lupus-Prone Mice

Systemic lupus erythematosus (SLE) is an autoimmune disorder with a high prevalence of renal disease. The progression of SLE is tracked by plasma double-stranded (ds) DNA autoantibodies. We have used an established model of SLE, female NZBWF1 mice, to determine mechanisms associated with SLE-induced renal disease. Typically, mice arrive by truck from Maine at 5-6 weeks of age and are not manipulated until 30-35 weeks when renal inflammation/injury is evident. Based on anecdotal observations in different cohorts of SLE mice, we hypothesized that seasonal factors, along with the stress associated with travel in early life, accelerate disease course in aged SLE mice. We performed a retrospective analysis of 5-6 week old female NZBWF1 mice ordered between 2015-2019 and divided them into two groups based on their date of arrival: summer (April-September; n=38) and winter (October-March; n=51). Average temperature on dates of arrival was higher in summer (78.5 ± 1.8 vs. 52.5 ± 1.9 °F; p< 0.001). Plasma dsDNA autoantibodies at 34-35 weeks was higher in SLE mice that arrived in summer (6.0e5 ± 8.6e4 vs. 4.1e5 ± 5.1e4 U/mL; p=0.049) and this coincided with higher indices of renal injury in SLE mice that arrived in summer (urinary albumin: 13.3e3 ± 2.6e3 vs. 6.0e3 ± 1.5e3 ug/mL; p=0.0096). Our findings suggest early life stress compounded with seasonal factors modulate autoimmunity. Future studies will investigate biochemical processes associated with warmer temperatures and their impact on the progression of SLE-associated renal disease.