Terminal Complement Complex (C5b-9) in Children with Recurrent Hemolytic Uremic Syndrome

Prüfer, Friederike; Scheiring, Johanna; Sautter, Sabine; Jensen, Dorthe Bødker; Treichl, Ruth; Würzner, Reinhard; Zimmerhackl, L. B.

doi:10.1055/s-2006-939768

Cited by 22 publications

(24 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The serum TCC levels did not differ between carriers and healthy family members. Another report describes a modest elevation of TCC levels in 17 patients suffering from recurrent HUS (18). Whether these results were obtained during active disease or remission is not described.…”

Section: Discussionmentioning

confidence: 99%

A Large Family with a Gain-of-Function Mutation of Complement C3 Predisposing to Atypical Hemolytic Uremic Syndrome, Microhematuria, Hypertension and Chronic Renal Failure

Lhotta

Janecke

Scheiring

et al. 2009

Clinical Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

Design, setting, participants, & measurements: A large family with a C3 R570Q mutation is described. Clinical and laboratory findings of carriers of the mutation and unaffected family members are reported.Results: The index patient suffered from recurrent aHUS at age 22 and developed end-stage renal failure. Of 24 family members, nine harbored the C3 R570Q mutation. Carriers showed reduced or borderline C3 levels. Arterial hypertension was found in six family members, microhematuria in five and chronic kidney disease stage 3 in two elderly carrier patients. Despite marked consumption of C3, serum terminal complement complex levels were not elevated in carriers compared with other family members.Conclusions: The penetrance of the C3 R570Q mutation to induce aHUS is incomplete and lower compared with mutations in other genes predisposing to the disease. The mutation is possibly also associated with hypertension, hematuria and chronic kidney disease, all of which may represent consequences of long-term complement activation in the renal vasculature.

show abstract

Section: Discussionmentioning

confidence: 99%

A Large Family with a Gain-of-Function Mutation of Complement C3 Predisposing to Atypical Hemolytic Uremic Syndrome, Microhematuria, Hypertension and Chronic Renal Failure

Lhotta

Janecke

Scheiring

et al. 2009

Clinical Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

show abstract

“…Plasma levels of complement components C3 (54) and terminal complement complex (TCC) (40,66) were measured by enzyme-linked immunosorbent assay. Levels of C3a were measured by a commercial enzyme-linked immunosorbent assay kit (Quidel) as recommended by the manufacturer.…”

Section: Methodsmentioning

confidence: 99%

Potent Human Immunodeficiency Virus-Neutralizing and Complement Lysis Activities of Antibodies Are Not Obligatorily Linked

Huber

Wyl

Ammann

et al. 2008

J Virol

View full text Add to dashboard Cite

To evaluate the contribution of complement-mediated lysis to the in vivo activities of neutralizing antibodies, we analyzed the influence of complement activation on treatment success in a recent passive immunization trial with the neutralizing monoclonal antibodies 2G12, 2F5, and 4E10. Administration of monoclonal antibodies led to an immediate, high activation of the complement system even in the absence of viremia in the 14 participating human immunodeficiency virus-infected individuals. Lysis activity measured in patient plasma increased during passive immunization; however, the increases were modest and only partially attributable to the administration of antibodies. We found that unlike neutralization activity, lysis activity was not associated with treatment success in this trial. Compared to complement lysis mounted by the polyclonal antibody response in vivo, monoclonal antibodies were weak inducers of this activity, suggesting that polyclonal responses are more effective in reaching the required threshold of complement activation. Importantly, strong neutralization activity of the monoclonal antibodies did not predict complement lysis activity against patient and reference viruses, suggesting that these activities are not linked. In summary, our data support the notion that the in vivo activities of 2G12, 2F5, and 4E10 are likely due to direct neutralization or Fc receptor-mediated mechanisms such as phagocytosis and antibody-dependent cellular cytotoxicity.

show abstract

“…20,21 Serum concentration of the soluble membrane attack complex (sC5b-9) at the time of TMA diagnosis and in 20 consecutive time-matched HSCT recipients without TMA was tested by enzyme-linked immunosorbent assay at the CCHMC Hematology Clinical Laboratory (normal 72-244 ng/mL). 13,22,23 …”

Section: Laboratory Monitoringmentioning

confidence: 99%

Diagnostic and risk criteria for HSCT-associated thrombotic microangiopathy: a study in children and young adults

Jodele

Davies

Lane

et al. 2014

Blood

342

443

View full text Add to dashboard Cite

• Proteinuria and elevated markers of complement activation at TMA diagnosis are associated with poor outcome.• Clinical interventions should be considered in HSCT patients with these high-risk features at the time TMA is diagnosed.Transplant-associated thrombotic microangiopathy (TMA) leads to generalized endothelial dysfunction that can progress to multiorgan injury, and severe cases are associated with poor outcomes after hematopoietic stem cell transplantation (HSCT). Identifying patients at highest risk for severe disease is challenging. We prospectively evaluated 100 consecutive HSCT recipients to determine the incidence of moderate and severe TMA and factors associated with poor overall outcomes. Thirty-nine subjects (39%) met previously published criteria for TMA. Subjects with TMA had a significantly higher nonrelapse mortality (43.6% vs 7.8%, P < .0001) at 1 year post-HSCT compared with those without TMA. Elevated lactate dehydrogenase, proteinuria on routine urinalysis, and hypertension were the earliest markers of TMA. Proteinuria (>30 mg/dL) and evidence of terminal complement activation (elevated sC5b-9) in the blood at the time of TMA diagnosis were associated with very poor survival (<20% at 1 year), whereas all TMA subjects without proteinuria and a normal sC5b-9 serum concentration survived (P < .01). Based on these prospective observations, we conclude that severe TMA occurred in 18% of HSCT recipients in our cohort and propose an algorithm to identify the highest-risk patients who might benefit from prompt clinical interventions. (Blood. 2014;124(4):645-653)

show abstract

Terminal Complement Complex (C5b-9) in Children with Recurrent Hemolytic Uremic Syndrome

Cited by 22 publications

References 10 publications

A Large Family with a Gain-of-Function Mutation of Complement C3 Predisposing to Atypical Hemolytic Uremic Syndrome, Microhematuria, Hypertension and Chronic Renal Failure

A Large Family with a Gain-of-Function Mutation of Complement C3 Predisposing to Atypical Hemolytic Uremic Syndrome, Microhematuria, Hypertension and Chronic Renal Failure

Potent Human Immunodeficiency Virus-Neutralizing and Complement Lysis Activities of Antibodies Are Not Obligatorily Linked

Diagnostic and risk criteria for HSCT-associated thrombotic microangiopathy: a study in children and young adults

Contact Info

Product

Resources

About