| First Author | Ueda Y | Year | 2018 |
| Journal | J Am Soc Nephrol | Volume | 29 |
| Issue | 7 | Pages | 1928-1937 |
| PubMed ID | 29858280 | Mgi Jnum | J:293121 |
| Mgi Id | MGI:6436115 | Doi | 10.1681/ASN.2017121244 |
| Citation | Ueda Y, et al. (2018) Blocking Properdin Prevents Complement-Mediated Hemolytic Uremic Syndrome and Systemic Thrombophilia. J Am Soc Nephrol 29(7):1928-1937 |
| abstractText | Background Properdin (P) is a positive regulator of the alternative pathway of complement activation. Although P inhibition is expected and has been shown to ameliorate the alternative pathway of complement-mediated tissue injury in several disease models, it unexpectedly exacerbated renal injury in a murine model of C3 glomerulopathy. The role of P in atypical hemolytic uremic syndrome (aHUS) is uncertain.Methods We blocked P function by genetic deletion or mAb-mediated inhibition in mice carrying a factor H (FH) point mutation, W1206R (FH(R/R)), that causes aHUS and systemic thrombophilia with high mortality.Results P deficiency completely rescued FH(R/R) mice from premature death and prevented thrombocytopenia, hemolytic anemia, and renal disease. It also eliminated macrovessel thrombi that were prevalent in FH(R/R) mice. All mice that received a function-blocking anti-P mAb for 8 weeks survived the experimental period and appeared grossly healthy. Platelet counts and hemoglobin levels were significantly improved in FH(R/R) mice after 4 weeks of anti-P mAb treatment. One half of the FH(R/R) mice treated with an isotype control mAb but none of the anti-P mAb-treated mice developed stroke-related neurologic disease. Anti-P mAb-treated FH(R/R) mice showed largely normal renal histology, and residual liver thrombi were detected in only three of 15 treated mice.Conclusions These results contrast with the detrimental effect of P inhibition observed in a murine model of C3 glomerulopathy and suggest that P contributes critically to aHUS pathogenesis. Inhibition of P in aHUS may be of therapeutic benefit. |
