biostudies-literatureChan ECIntramural NIH HHS2628-2646https://www.ebi.ac.uk/biostudies/studies/S-EPMC11602389biostudies-literatureUnknown44(12)<h4>Background</h4>Vascular leakage is a deadly complication of severe infections, ranging from bacterial sepsis to malaria. Worldwide, septicemia is among the top 10 causes of lethality because of the shock and multiorgan dysfunction that arise from the host vascular response. In the monoclonal gammopathy-associated capillary leak syndrome (MG-CLS), even otherwise mundane infections induce recurrent septic-like episodes of profound microvascular hyperpermeability and shock. There are no defined genetic risk factors for MG-CLS or effective treatments for acute crises.<h4>Methods</h4>We characterized predicted loss-of-function mutations in PARP15 (poly[ADP-ribose] polymerase 15), a protein of unknown function that is absent in mice, in patients with MG-CLS. We analyzed barrier function in PArteriosclerosis, thrombosis, and vascular biology&lt;i&gt;PARP15&lt;/i&gt; Is a Susceptibility Locus for Clarkson Disease (Monoclonal Gammopathy-Associated Systemic Capillary Leak Syndrome).PMC11602389ZIA AI001083Druey KMOlano MRSchaible NAblooglu AJChan ECParikh SMKrishnan RZhao MGhosh CCGanesan SDesai ALack JBChen Xfalse&lt;i&gt;PARP15&lt;/i&gt; Is a Susceptibility Locus for Clarkson Disease (Monoclonal Gammopathy-Associated Systemic Capillary Leak Syndrome).<h4>Background</h4>Vascular leakage is a deadly complication of severe infections, ranging from bacterial sepsis to malaria. Worldwide, septicemia is among the top 10 causes of lethality because of the shock and multiorgan dysfunction that arise from the host vascular response. In the monoclonal gammopathy-associated capillary leak syndrome (MG-CLS), even otherwise mundane infections induce recurrent septic-like episodes of profound microvascular hyperpermeability and shock. There are no defined genetic risk factors for MG-CLS or effective treatments for acute crises.<h4>Methods</h4>We characterized predicted loss-of-function mutations in PARP15 (poly[ADP-ribose] polymerase 15), a protein of unknown function that is absent in mice, in patients with MG-CLS. We analyzed barrier function in P2024-01-01T00:00:00Z2024 Dec2026-06-10T05:07:28.965Z2026-06-10T03:07:13.845ZS-EPMC116023893947976910.1161/atvbaha.124.32152210.1161/ATVBAHA.124.321522