Familial relapsing haemolytic uraemic syndrome and complement factor H deficiency

Warwicker, Paul; Donne, Rosie; Goodship, Judith A.; Goodship, Timothy H.J.; Howie, A J; Kumararatne, D. S.; Thompson, Rohan; Taylor, Chris

doi:10.1093/ndt/14.5.1229

Cited by 61 publications

(38 citation statements)

References 4 publications

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“…This is not unexpected as IF, like CFH, is predominantly synthesized by the liver and thus a renal allograft will not correct the underlying defect. From individuals reported in the literature and unpublished from our own cohort, the recurrence rate in those with CFH mutations and/or CFH deficiency is approximately 80% (2,4,6,7,(25)(26)(27)(28)(29)(30).…”

Section: Discussionmentioning

confidence: 97%

Mutations in Complement Factor I Predispose to Development of Atypical Hemolytic Uremic Syndrome

Kavanagh¹,

Kemp²,

Mayland³

et al. 2005

Journal of the American Society of Nephrology

315

168

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Mutations in the plasma complement regulator factor H (CFH) and the transmembrane complement regulator membrane co-factor protein (MCP) have been shown to predispose to atypical hemolytic uremic syndrome (HUS). Both of these proteins act as co-factors for complement factor I (IF). IF is a highly specific serine protease that cleaves the ␣-chains of C3b and C4b and thus downregulates activation of both the classical and the alternative complement pathways. This study looked for IF mutations in a panel of 76 patients with HUS. Mutations were detected in two patients, both of whom had reduced serum IF levels. A heterozygous bp change, c.463 G>A, which results in a premature stop codon (W127X), was found in one, and in the other, a heterozygous single base pair deletion in exon 7 (del 922C) was detected. Both patients had a history of recurrent HUS after transplantation. This is in accordance with the high rate of recurrence in patients with CFH mutations. Patients who are reported to have mutations in MCP, by contrast, do not have recurrence after transplantation. As with CFH-and MCPassociated HUS, there was incomplete penetrance in the family of one of the affected individuals. This study provides further evidence that atypical HUS is a disease of complement dysregulation.

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Section: Discussionmentioning

confidence: 97%

Mutations in Complement Factor I Predispose to Development of Atypical Hemolytic Uremic Syndrome

Kavanagh¹,

Kemp²,

Mayland³

et al. 2005

Journal of the American Society of Nephrology

315

168

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“…Eleven patients (7 in the literature [8,36,37,38,39,40], 3 in Hôpital des Enfants-Malades, P. Niaudet, unpublished data, 1 in Hôpital Robert Debré, C. Loirat, unpublished data) with HUS associated with factor H deficiency have a documented post-transplant course (Tables 3 and 4). HUS started during infancy or childhood in 8, during adulthood in 3.…”

Section: The Risk Of Hus Recurrence In Patients With Hus Associated Wmentioning

confidence: 99%

“…Another patient lost his graft on day 27 from either vascular rejection or recurrence of HUS [38]. The 5 other patients had no recurrence of HUS after transplantation, although 2 lost their graft from early vascular rejection with some thrombotic microangiopathy lesions in 1 (P. Niaudet, unpublished data), without thrombotic microangiopathy lesions in the other [39]. Seven patients with HUS and normal factor H concentrations, but with mutations in factor H gene, have been transplanted [8].…”

Section: The Risk Of Hus Recurrence In Patients With Hus Associated Wmentioning

confidence: 99%

The risk of recurrence of hemolytic uremic syndrome after renal transplantation in children

Loirat

Niaudet

2003

Pediatric Nephrology

136

105

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We reviewed the literature to analyze the risk of recurrence of hemolytic uremic syndrome (HUS) after renal transplantation in children. Among 118 children transplanted after post-diarrheal (D+) HUS, 1 (0.8%) had recurrence with graft loss. Among 63 children transplanted after HUS not associated with a prodrome of diarrhea (D-) of unknown mechanism, 13 (21%) had recurrence with graft loss. Of 11 patients with HUS associated with factor H deficiency who were transplanted, 5 lost the graft because of recurrence. Of 7 patients with HUS associated with normal factor H concentration but mutations in factor H gene who were transplanted, probably 2 had recurrence. Three patients with HUS associated with low serum C3, but no factor H deficiency or mutation lost their graft because of recurrence. The risk of recurrence in the autosomal recessive forms of HUS of unknown mechanism is not documented in children, but is around 60% in adults. A similar risk has been reported in the autosomal dominant forms. The only transplant patient with a constitutional deficiency of von Willebrand factor-cleaving protease had recurrence. Further efforts to document the post-transplant course of patients with D- HUS and progress in the understanding of the mechanisms and genetics of the disease are needed to allow more accurate prediction of the recurrence risk and to define therapeutic approaches.

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“…Factor H abnormalities are also associated with excess C3b and paramesangial deposits, although the associated nephritis is usually mild and hypocomplementemia is usually severe (7). Factor H abnormalities have been observed in a variety of renal diseases, including familial hemolytic uremic syndrome (26), collagen III nephropathy (27), and atypical MPGN type II (28).…”

Section: Discussionmentioning

confidence: 99%

Linkage of a Gene Causing Familial Membranoproliferative Glomerulonephritis Type III to Chromosome 1

Neary¹,

Conlon²,

Croke³

et al. 2002

Journal of the American Society of Nephrology

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Familial relapsing haemolytic uraemic syndrome and complement factor H deficiency

Abstract: These findings represent further evidence of the association between factor H dysfunction and HUS.

Cited by 61 publications

References 4 publications

Mutations in Complement Factor I Predispose to Development of Atypical Hemolytic Uremic Syndrome

Mutations in Complement Factor I Predispose to Development of Atypical Hemolytic Uremic Syndrome

The risk of recurrence of hemolytic uremic syndrome after renal transplantation in children

Linkage of a Gene Causing Familial Membranoproliferative Glomerulonephritis Type III to Chromosome 1

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