Novel biomarker and easy to perform ELISA for monitoring complement inhibition in patients with atypical hemolytic uremic syndrome treated with eculizumab.

Atypical hemolytic uremic syndrome (aHUS) is a devastating disease characterized by thrombus formation in the microvasculature and is associated with complement dysregulation. The recommended treatment is eculizumab, an humanized monoclonal antibody, which binds complement protein C5 and thereby preventing the assembly of the terminal complement complex (TCC, soluble C5b-9) and the generation of C5a, an anaphylatoxin. The objective of the study was to identify a reliable biomarker, which estimates the degree of complement inactivation under normal and pathophysiological conditions, such as an infection.

Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome.

Background: Atypical hemolytic-uremic syndrome is a genetic, life-threatening, chronic disease of complement-mediated thrombotic microangiopathy. Plasma exchange or infusion may transiently maintain normal levels of hematologic measures but does not treat the underlying systemic disease.

Methods: We conducted two prospective phase 2 trials in which patients with atypical hemolytic-uremic syndrome who were 12 years of age or older received eculizumab for 26 weeks and during long-term extension phases.

Complement factor H-related protein 1 deficiency and factor H antibodies in pediatric patients with atypical hemolytic uremic syndrome.

Background And Objectives: This study evaluated the relevance of complement factor H (CFH)-related protein (CFHR) 1 deficiency in pediatric patients with atypical hemolytic uremic syndrome (aHUS) by evaluating both the frequency of deletions in CFHR1 and the presence of complement factor H (CFH) antibodies.

Design, Setting, Participants, & Measurements: A total of 116 patients (mainly from central Europe) and 118 healthy blood donors were included from 2001 to 2012. The presence of CFHR1 gene deletions was determined in 90 pediatric patients with aHUS and 118 controls by an easy, fast, and cheap PCR assay; 100 patients with aHUS and 42 controls were tested for CFH antibodies by ELISA.

Need for long-term follow-up in enterohemorrhagic Escherichia coli-associated hemolytic uremic syndrome due to late-emerging sequelae.

Background: The aim of this study was to evaluate the long-term prognosis of children with hemolytic uremic syndrome (HUS).

Methods: Over a 6-year period, 619 pediatric patients with the clinical diagnosis of HUS were registered in Austria and Germany, and a subset (n = 274) was prospectively followed up for 5 years.

Results: Infection with enterohemorrhagic Escherichia coli (EHEC) was confirmed in 79% of cases.

Immunogenicity of meningococcus C vaccination in a patient with atypical hemolytic uremic syndrome (aHUS) on eculizumab therapy.

We report successful kidney transplantation in a 10-yr-old boy with aHUS and heterozygous factor H mutation using the terminal complement inhibitor eculizumab to avoid recurrence of aHUS in the renal graft. Vaccination against meningococcus C (Men C) is essential in patients with dysfunction of the complement system, as induced by eculizumab. In our patient, we report waning SBA titers but maintenance of protective SBA titers (≥1:8) after kidney transplantation under immunosuppressive therapy with mycophenolate mofetil, tacrolimus, steroids, and eculizumab over a 27-month observational period.