GALT in lupus nephritis V1
Research type
Research Study
Full title
Gut-associated lymphoid tissue in lupus nephritis and controls
IRAS ID
345775
Contact name
Jo Spencer
Contact email
Sponsor organisation
King's College London
Duration of Study in the UK
3 years, 0 months, 1 days
Research summary
Systemic lupus erythematosus is a debilitating autoimmune disease in which the immune system makes autoantibodies to DNA. In the most severe cases, complexes of antibody DNA and complement may be deposited in the kidney leading to the most life threatening manifestation of lupus: lupus nephritis.
We have identified several ways in which the immune system in the gut and gut microbiota are linked to disease severity in lupus, including:
-That the gut is involved in the development of a subset of human B cells in health and also that this subset of B cells and the pathways along which it develops are selectively depleted in lupus nephritis.
- That features of lupus including associated cells and targets of autoantibodies, are selectively located in the gut in a place where the immune system directly meets the gut microbiota.
- That animal models that had previously supported a suggestion that the anti-DNA antibodies in lupus were driven by DNA shed by dying cells were flawed. We saw that a key enzyme that mediates the dispersal of DNA outside cells has a different distribution in humans and mice. Whilst in mice it is associated with digestion of DNA from dying cells, in humans it is not. Rather it is associated with digestion of DNA from gut bacteria in humans.
Here we plan to look directly at the immune system in gut in patients of with lupus nephritis and controls by requesting patients to consent to donate biopsies taken through the flexible sigmoidoscope. Using these samples we will ask, first, if the immune system profile in changes in disease compared to controls. Second, is bacterial transit into tissue any different in disease compared to controls. Third, are mechanisms that normally disperse DNA from bacteria in health (including DNASE1L3 and C1q) any different in disease compared to controls.
REC name
London - Camden & Kings Cross Research Ethics Committee
REC reference
26/LO/0085
Date of REC Opinion
6 Mar 2026
REC opinion
Further Information Favourable Opinion