A study led by St. Jude Children’s Research Hospital has found evidence suggesting that patrolling monocytes may drive glomerulonephritis; inflammation of the kidneys, in patients with lupus. The findings overturn the previously held notion that lupus is solely the result of B cell dysfunction.
Lupus is a chronic autoimmune disease that affects adults as well as children and adolescents. There is a range of symptoms with lupus, including fatigue and pain in numerous tissues in the body such as the joints, kidneys, brain, heart, and lungs. Among patients with lupus, 40-70% develop nephritis and 10-30% of those individuals progress to end-stage kidney disease requiring dialysis or kidney transplantation.
The current therapeutic approach for lupus-related glomerulonephritis is based on general immuno-suppressive agents with significant side effects. Experimental therapies target B cells; however, such treatments have proven largely ineffective in clinical testing and therefore have not been approved for use. Patrolling monocytes are a type of immune cell previously link to inflammation in blood vessels. Their dominance in glomerulonephritis opens the door for novel treatment strategies.
Treatments for glomerulonephritis
The findings indicate that treatments for glomerulonephritis that do not address the patrolling monocytes may be ineffective. They are looking at the immune signaling pathways and the genetic regulation of patrolling monocytes to identify new therapeutic targets.” The researchers developed a mouse model based on the human lupus susceptibility locus TNFAIP3-interacting protein 1 (TNIP1, also called ABIN1).
This gene is the same between humans; producing a disease model that closely mimics human lupus. In addition to this work, the researchers confirmed their findings in patient samples. To figure out which cells appearing in the kidney glomeruli, the investigators conducted an antibody screen; using cellular markers to identify cell types.
This effort found that the cells in question were marked with CD43; a hallmark of patrolling monocytes. There is more work to do to understand why these cells get stuck in the kidneys in patients with lupus,” Haecker said. “Exploring these mechanisms may lead us to new drug targets while continuing to inform our view of lupus and the biology that underlies symptoms with the disease.”