New cause of kidney damage in lupus identified

Researchers at Charité – Universitätsmedizin Berlin, the German Rheumatology Research Center (DRFZ) and the Max Delbrück Center (MDC) have discovered that specialised immune cells, known as innate lymphoid cells (ILC), play a key role in kidney damage (lupus nephritis) in lupus patients. These cells exacerbate the organ damage that was mainly associated to autoantibodies until now. The study, published in Nature, challenges traditional views and could influence future antibody therapies for lupus. Lupus affects around five million people worldwide, mainly young women, and can lead to severe kidney damage.

The research team led by Antigoni Triantafyllopoulou and Andreas Diefenbach, both Charité-liaison group leaders at the DRFZ, and Masatoshi Kanda from the MDC, in cooperation with Mir-Farzin Mashreghi from the DRFZ, examined the entire kidney cell repertoire  using single-cell RNA sequencing. They analysed almost 100,000 kidney and immune cells to identify the circuits controlled by the ILCs in order to understand the mechanism of lupus nephritis.

Until now, it was assumed that autoantibodies alone cause kidney inflammation. However, this study has shown that specialised ILC with the receptor NKp46, play a key role in triggering kidney damage. These cells produce the protein GM-CSF, which leads to the proliferation of macrophages that cause tissue damage. By blocking NKp46, the kidney damage was significantly reduced, even though the amount of autoantibodies did not change.

These findings could lead to the development of new antibody therapies to prevent severe kidney damage in lupus patients.