Rhea Bhargava, MD

Elucidating Sex Differences in Systemic Lupus Erythematosus by Utilizing Metabolic and Glycomic Profiles​

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Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that affects mainly women, but the disease severity is worse in males with an increased risk of developing lupus nephritis (LN). The cause of these differences remains unclear. Our recent investigations have shown differences in kidney and immune cell metabolism in SLE with and without nephritis. The epidemiology of kidney disease also differs by sex, with a greater risk of kidney failure in men. New data suggest that sex differences in proximal tubule metabolism may contribute to these differing outcomes. Changes in metabolic pathways not only support the biosynthetic and bioenergetic needs of a cell but also control the fate or function of immune cells. We have previously shown that metabolism of kidney cells in lupus can influence the proliferation of T cells in the kidney and hence influence the progression of lupus nephritis. B cells play an essential role in immune complex mediated disease like SLE and lupus nephritis. We have also demonstrated that changes in IgG glycosylation can lead to podocyte injury through metabolic reprogramming. In this proposal, we hypothesize that there is a link between altered metabolism in lupus and reprogramming of B cells eventually leading to aberrant IgG glycosylation and the development of lupus nephritis and this may contribute to the sex specific differences noted in SLE.