Discoveries about the basic workings of endothelial cells could lead to a diagnostic test for the serious kidney disease known as hemolytic uremic syndrome (HUS).
HUS is a potentially life-threatening condition and often occurs after gastrointestinal infection with Escherichia coli
O157:H7, which produces Shiga toxins (Stx) that cause hemolytic anemia, thrombocytopenia, and renal injury.
Scientists at University of Toronto (ON, Canada) discovered a biological pathway never before known to have played a role in the development of HUS. Specifically, they found that the toxin can increase the level of a chemokine, namely stromal cell-derived factor-1 (SDF-1), and its receptor, C-X-C chemokine receptor type 4 (CXCR4). Chemokines are small secreted proteins that stimulate cells to move or migrate. CXCR4 was already known to stimulate the release and migration of the precursors of white blood cells from bone marrow, to change how blood vessels grow and to help the AIDS virus enter cells.
Blood tests were performed on children with E. coli
and all measurements of SDF-1 were performed on blinded samples by a sandwich enzyme-linked immunosorbent assay (ELISA) (R&D Systems, Minneapolis, MN, USA). The results indicated that those who went on to develop HUS had as much as four times higher levels of the protein SDF-1, than other children with E. coli
who did not go on to develop HUS. This suggests that a blood test could be used to predict who is most likely to develop the potentially fatal HUS, meaning they could be monitored more closely. The scientists found that too much communication between SDF-1 and CXCR4 molecules can also impact the development of HUS in animals and humans.
Philip A. Marsden, MD, FRCPC, who is a nephrologist at Saint Michael’s Hospital (Toronto, ON, Canada) and senior author of the study, said, "A safe water supply and clean food supply chain is the most important step in preventing HUS caused by E. coli
. If we can measure SDF-1 levels in real time during an E. coli
outbreak and confirm these findings, then we have a strong case for a trial of CXCR4 antagonists in patients with toxin-producing E. coli
to see if it prevents or improves cases of HUS.” The study was published on January 9, 2012, in the Journal of Clinical Investigation.
University of Toronto
Saint Michael’s Hospital