Familial hypercholesterolemia (FH, OMIM number #143890), a life-threatening monogenic disorder characterized by high levels of low-density lipoprotein cholesterol (LDL-C), is classified into dominant and recessive types (1). The form FH may result from mutations in the LDLR, APOB, PCSK9 genes (2). However, receptor (LDLR) adaptor protein-1 (LDLRAP1) gene cause an autosomal inheritance pattern c...

Several studies have demonstrated genetic predisposition in non-shigatoxin-associated hemolytic uremic syndrome (HUS), involving regulatory proteins of the complement alternative pathway: Factor H (FH) and membrane co-factor protein (CD46). Regarding the observations of thrombotic thrombocytopenic purpura patients, in whom a von Willebrand factor protease (ADAMST-13) deficiency may be inherited...

Meningococcal factor H-binding protein (fHbp) is a promising antigen that is part of two vaccines in clinical development. The protein specifically binds human complement factor H (fH), which downregulates complement activation on the bacterial surface and enables the organism to evade host defenses. In humans, the vaccine antigen forms a complex with fH, which may affect anti-fHbp antibody rep...

Serum resistance, or resistance to complement-mediated killing, is a key virulence property of microbial pathogens. Rck is a 17-kDa outer membrane protein encoded on the virulence plasmid of Salmonella enterica serovars Typhimurium and Enteritidis. When expressed in either Escherichia coli or S. enterica Typhimurium, Rck confers serum resistance independent of LPS length. Recently, the Rck homo...

Tick-borne relapsing fever in North America is primarily caused by the spirochete Borrelia hermsii. The pathogen employs multiple strategies, including the acquisition of complement regulators and antigenic variation, to escape innate and humoral immunity. In this study we identified in B. hermsii a novel member of the complement regulator-acquiring surface protein (CRASP) family, designated Bh...

INTRODUCTION Complement activation is involved in rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and atypical hemolytic uremic syndrome (aHUS). Autoantibodies to complement inhibitor factor H (FH), particularly in association with deletions of the gene coding for FH-related protein 1 (CFHR1), are associated with aHUS. METHODS Autoantibodies against FH, factor I (FI) and C4b-bin...

BACKGROUND AND OBJECTIVE Neisseria meningitidis is a leading cause of meningitis and sepsis worldwide. The factor H binding protein (fHBP) is a key virulence factor of Neisseria meningitidis that is able to selectively bind to human factor H, the key regulator of the alternative complement pathway, which it has important implications for meningococcal pathogenesis and vaccine design. The aims o...

In this report we compare the cord blood lipoproteins of a newborn boy homozygote who has low density lipoprotein (LDL) receptor-defective familial hypercholesterolemia (FH) with the lipoproteins from cord blood of normal newborns. Plasma LDL-cholesterol and apoprotein (Apo)B were 612 and 233 mg/dl (vs. 31+/-16 and 24+/-12 mg/dl, respectively, for normals, n = 21). LDL-cholesterol/ApoB ratio wa...

The Fumarase (Fumarate Hydratase, FH) is a tumor suppressor gene whose germline heterozygous mutations predispose to hereditary leiomyomatosis and renal cell cancer (HLRCC). The FH gene encodes an enzyme of the Krebs cycle, functioning as a homotetramer and catalyzing the hydration of fumarate to malate. Among the numerous FH mutations reported so far, the R190H missense mutation is the most fr...

In an attempt to evade annihilation by the vertebrate complement system, many microbes capture factor H (FH), the key soluble complement-regulating protein in human plasma. However, FH is normally an active complement suppressor exclusively on self-surfaces and this selective action of FH is pivotal to self versus non-self discrimination by the complement system. We investigated whether the bac...