Membrane cofactor protein (MCP) haplotype, which predisposes to atypical hemolytic and uremic syndrome, has no consequence on neutrophils and endothelial cells MCP levels or on HUVECs ability to activate complement

Frimat, Marie; Roumenina, Lubka; Tabarin, Fanny; Halbwachs‐Mecarelli, Lise; Frémeaux‐Bacchi, Véronique

doi:10.1016/j.imbio.2012.08.168

Cited by 5 publications

(8 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 80,82 Reporter gene assays have suggested that this haplotype reduces transcriptional activity by 25%, 80 however, this did not correlate with MCP cell surface expression in vivo. 80,86,87 Further experiments on human umbilical vein endothelial cells (HUVECs) with risk and protective MCP haplotypes showed equal MCP expression whether in the resting state, after cytokine treatment, or free heme treatment. Likewise, no increase in complement deposition could be shown on HUVECs bearing the MCP risk haplotype.…”

Section: Genetic Susceptibility Factorsmentioning

confidence: 99%

See 1 more Smart Citation

Atypical Hemolytic Uremic Syndrome

Kavanagh

Goodship

Richards

2013

Seminars in Nephrology

304

367

View full text Add to dashboard Cite

SummaryHemolytic uremic syndrome (HUS) is a triad of microangiopathic hemolytic anemia, thrombocytopenia, and acute renal failure. The atypical form of HUS is a disease characterized by complement overactivation. Inherited defects in complement genes and acquired autoantibodies against complement regulatory proteins have been described. Incomplete penetrance of mutations in all predisposing genes is reported, suggesting that a precipitating event or trigger is required to unmask the complement regulatory deficiency. The underlying genetic defect predicts the prognosis both in native kidneys and after renal transplantation. The successful trials of the complement inhibitor eculizumab in the treatment of atypical HUS will revolutionize disease management.

show abstract

Section: Genetic Susceptibility Factorsmentioning

confidence: 99%

“…Likewise, no increase in complement deposition could be shown on HUVECs bearing the MCP risk haplotype. 87 …”

Section: Genetic Susceptibility Factorsmentioning

confidence: 99%

Atypical Hemolytic Uremic Syndrome

Kavanagh

Goodship

Richards

2013

Seminars in Nephrology

304

367

View full text Add to dashboard Cite

show abstract

“…A CD46 haplotype ( CD46 ggaac ) block has been associated with a two- to threefold increased risk of complement-mediated aHUS [ 22 – 24 ]. This encompasses 2 SNPs in the promoter region of CD46, and reporter gene assays have suggested that this haplotype reduces transcriptional activity by 25% albeit without decreased CD46 cell surface expression in vivo [ 24 , 25 ]. A CFH haplotype ( CFH -H3; tgtgt) has been shown to increase the risk of complement-mediated aHUS two- to fourfold [ 22 , 26 ].…”

Section: Pathologymentioning

confidence: 99%

Diseases of complement dysregulation—an overview

Wong

Kavanagh

2018

Semin Immunopathol

View full text Add to dashboard Cite

Atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3G), and paroxysmal nocturnal hemoglobinuria (PNH) are prototypical disorders of complement dysregulation. Although complement overactivation is common to all, cell surface alternative pathway dysregulation (aHUS), fluid phase alternative pathway dysregulation (C3G), or terminal pathway dysregulation (PNH) predominates resulting in the very different phenotypes seen in these diseases. The mechanism underlying the dysregulation also varies with predominant acquired autoimmune (C3G), somatic mutations (PNH), or inherited germline mutations (aHUS) predisposing to disease. Eculizumab has revolutionized the treatment of PNH and aHUS although has been less successful in C3G. With the next generation of complement therapeutic in late stage development, these archetypal complement diseases will provide the initial targets.

show abstract

“…expression in vivo. 80,86,87 Further experiments on human umbilical vein endothelial cells (HUVECs) with risk and protective MCP haplotypes showed equal MCP expression whether in the resting state, after cytokine treatment, or free heme treatment. Likewise, no increase in complement deposition could be shown on HUVECs bearing the MCP risk haplotype.…”

Section: Genetic Susceptibility Factorsmentioning

confidence: 98%

“…Likewise, no increase in complement deposition could be shown on HUVECs bearing the MCP risk haplotype. 87 A SNP in C4b binding protein (R240H) was associated with aHUS in cohorts from the United Kingdom and France. C4b binding protein is the predominant classic pathway fluid phase regulator but also has weak AP regulatory activity.…”

Section: Genetic Susceptibility Factorsmentioning

confidence: 99%