A5083115353- Complement system in diseases
- Renal Diseases and Glomerulopathies
- Renal Transplantation Outcomes and Treatments
- Retinal Diseases and Treatments
- Blood Coagulation and Thrombosis Mechanisms
- Neurological Complications and Syndromes
- Pregnancy and preeclampsia studies
- Coagulation, Bradykinin, Polyphosphates, and Angioedema
- Hemoglobinopathies and Related Disorders
- Iron Metabolism and Disorders
- Blood groups and transfusion
- Adenosine and Purinergic Signaling
- Mosquito-borne diseases and control
- Immune Cell Function and Interaction
- Retinal Imaging and Analysis
- SARS-CoV-2 and COVID-19 Research
- Retinal Development and Disorders
- Diversity and Career in Medicine
- Renal and Vascular Pathologies
- Transplantation: Methods and Outcomes
- Hepatitis B Virus Studies
- Retinal and Optic Conditions
- Lysosomal Storage Disorders Research
- Polyomavirus and related diseases
- HIV/AIDS drug development and treatment
Washington University in St. Louis
2015-2025
University of Helsinki
2024
Jewish Hospital
2016
Barnes-Jewish Hospital
2016
The term atypical hemolytic uremic syndrome has been in use since the mid-1970s. It was initially used to describe familial or sporadic form of as opposed epidemic, typical disease. Over time, evolved into being refer anything that is not Shiga toxin–associated syndrome. describes a heterogeneous group diseases disparate causes, circumstance makes defining disease-specific natural history and/or targeted treatment approaches challenging. A working specialty-specific experts thrombotic...
Abstract The genetic architecture of age-related macular degeneration (AMD) involves numerous variants, both common and rare, in the coding region complement factor H ( CFH ). While these variants explain high disease burden some families, they fail to pathology all. We selected families whose AMD was unexplained by known performed whole exome sequencing probe for other highly penetrant variants. identified four rare loss-of-function associated with AMD. Missense variant 1:196646753 (C192F)...
C3 glomerulopathy is a recently described form of CKD. C3GN subtype characterized by predominant deposits in the glomeruli and commonly result acquired or genetic abnormalities alternative pathway (AP) complement system. We identified first mutation gene (p. I734T) two related individuals diagnosed with C3GN. Immunofluorescence electron microscopy studies showed subendothelial space, associated unusual located near receptor 1 (CR1)-expressing podocytes. In vitro, this exhibited decreased...
Purpose: Factor I (FI) is a serine protease regulator of the complement system. Genetic variants in CFI are associated with advanced age-related macular degeneration (AAMD). However, clinical and functional impact these unknown. This study assessed significance rare using serum-based assay. Methods: Carriers (n = 78) without AAMD 28), noncarriers 49) AMD 44) were evaluated. Function FI was determined by measuring proteolytic cleavage C3b to iC3b, cofactor protein, H. Results: categorized...
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The objective of the study was to investigate role genetic variants in complement proteins pre-eclampsia.
<h2>Abstract</h2> The haemolytic uraemic syndromes (HUS) are a heterogeneous group of conditions only some which mediated by complement (CaHUS). We report the outcome 2023 International Society Nephrology HUS Forum where global panel experts considered current state art, identified areas uncertainty, and proposed optimal solutions. Areas uncertainty for future research included: nomenclature HUS; novel testing strategies; identification biomarkers; genetic predisposition to aHUS; dosing...
Abstract Thrombotic microangiopathy (TMA) is a challenging and serious complication of kidney transplantation that significantly impacts graft patient survival, occurring in 0.8–15% transplant recipients. TMA characterized by microangiopathic hemolytic anemia, thrombocytopenia, organ injury due to endothelial damage microthrombi formation small vessels. However, clinical features can range from renal-limited form, diagnosed only on biopsy, full-blown systemic manifestations, which include...
Abstract Age-related macular degeneration (AMD) is a complex neurodegenerative eye disease with behavioral and genetic etiology the leading cause of irreversible vision loss among elderly Caucasians. Functionally significant variants in alternative pathway complement have been strongly linked to disease. More recently, rare variant terminal has associated increased risk, Complement component 9 (C9) P167S. To assess functional consequence this variant, C9 levels were measured two independent...
Genetic testing has uncovered rare variants in complement proteins associated with thrombotic microangiopathy (TMA) and C3 glomerulopathy (C3G). Approximately 50% are classified as of uncertain significance (VUS). Clinical risk assessment patients carrying a VUS remains challenging primarily due to lack functional information, especially the context multiple confounding factors setting kidney transplantation. Our objective was evaluate clinicopathologic genetic TMA C3G transplant cohort. We...
Ninety percent of people with chronic kidney disease (CKD) remain undiagnosed, most at risk do not receive guideline-concordant testing, and disparities care outcomes exist across all stages the disease. To improve CKD diagnosis management primary care, National Kidney Foundation launched a collective impact (CI) initiative known as Show Me CKDintercept. The was implemented in Missouri, USA from January 2021 to June 2022, using data strategy, stakeholder engagement relationship mapping,...
Factor I (FI) is a serine protease inhibitor of the complement system. Heterozygous rare genetic variants in factor (CFI) are associated with advanced age-related macular degeneration (AMD). The clinical impact these unknown since majority have not been functionally characterized and classified as 'variants uncertain significance' (VUS). This study assessed functional significance VUS CFI. Our previous cross-sectional using serum-based assay demonstrated that CFI AMD can be categorized into...
Aim: Ravulizumab and eculizumab are complement C5 inhibitors approved for the treatment of atypical hemolytic uremic syndrome (aHUS). requires less frequent infusions than eculizumab, which may reduce burden. This study investigated patients' preferences impact both treatments on patient caregiver quality life. Materials & methods: Two surveys were conducted (one adult patients with aHUS one caregivers pediatric aHUS) to quantitatively assess preference patient- caregiver-reported...
Atypical hemolytic uremic syndrome (aHUS) is a rare thrombotic microangiopathy (TMA) characterized by the triad of microangiopathic anemia, thrombocytopenia, and acute kidney injury (AKI).1Goodship T.H. Cook H.T. Fakhouri F. et al.Atypical C3 glomerulopathy: conclusions from "Kidney Disease: Improving Global Outcomes" (KDIGO) Controversies Conference.Kidney Int. 2017; 91: 539-551Abstract Full Text PDF PubMed Scopus (276) Google Scholar,S1–S5 The disease features overactivity alternative...
Abstract Preeclampsia is a common multifactorial disease of pregnancy. Dysregulation the complement activation among emerging candidates responsible for pathogenesis. In targeted exomic sequencing study we identified 14 variants within nine genes coding components membrane attack complex (MAC, C5b-9) that are associated with preeclampsia. We found two rare missense in C5 gene predispose to preeclampsia (rs200674959: I1296V, OR (CI95) = 24.13 (1.25–467.43), p-value 0.01 and rs147430470:...