"It's generally thought that the presence of antibodies in the kidney indicates a problem with the immune system," Shaw says. "But our data suggest that antibodies and other proteins from the blood may normally pass through or become trapped in the filters of the kidney and that an important process is the removal or clearance of these proteins from the kidney."
The glomerular abnormalities in mice lacking one copy of CD2AP are very similar to a disease in humans called focal segmental glomerulosclerosis (FSGS), one of the most common forms of kidney disease. FSGS afflicts both children and adults, is more prevalent in African Americans and can be triggered by chronic infections such as HIV. Currently, the disease has no treatment or cure.
Shaw and his colleagues examined DNA from 45 African Americans with FSGS, 15 of whom also had HIV. They compared these individuals with 45 African Americans with HIV who did not have kidney problems. Ten of the individuals with FSGS had DNA changes in the CD2AP gene that were not found in the control group. Two of these patients had a genetic mutation that would be expected to block one of the two copies of their CD2AP gene, consistent with the idea that inheriting only one copy of the gene can lead to kidney disease.
"I think there are going to be many genes identified in the future that are involved in the clearance of these proteins from the kidney," Shaw says. "In this case, we identified at least two patients that lack one copy of CD2AP. We hope that more knowledge about such mutations will help us identify individuals predisposed to develop these diseases and potentially prevent them from becoming sick."