Clinical Features of Anti-Factor H Autoantibody–Associated Hemolytic Uremic Syndrome

Abstract

Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy that associates, in 70% of cases, with genetic or acquired disorders leading to dysregulation of the alternative pathway of complement. Autoantibody directed against Factor H causes at least 6% to 10% of aHUS cases, but only a few clinical reports are available. Here, we describe the clinical, biologic, genetic features, treatment, and outcome of 45 patients who presented with aHUS associated with anti-FH autoantibody. We found that this form of aHUS primarily affects children between 9 and 13 years old but it also affects adults. It presents with a high frequency of gastrointestinal symptoms and with extrarenal complications and has a relapsing course. Activation of the alternative pathway of complement at the onset of disease portends a poor prognosis. Early specific treatment may lead to favorable outcomes. These data should improve the recognition and diagnosis of this form of aHUS and help identify patients at high risk of a poor outcome.

Complement Factor H–Related Protein 1 Deficiency and Factor H Antibodies in Pediatric Patients with Atypical Hemolytic Uremic Syndrome

“…The age at disease onset in our cohort (mean age, 7.9 years) was similar to the published age range (37). Age at onset was significantly greater than that in patients with CFH-antibody negative cases (31,37).…”

“…The presence of CFH antibodies was associated with a significantly lower platelet nadir at disease onset compared with CFH antibody-negative patients, and even lower than described for the nonexclusively pediatric cohort (37). The platelet nadir in our cohort is quite close to the mean platelet nadir in ADAMTS 13 activity-deficient patients with thrombotic thrombocytopenia (42), which may lead to diagnostic difficulties.…”

“…Extrarenal complications in CFH antibody-positive aHUS during the first flare of disease were common, although CNS involvement was found in a significantly lower percentage of patients than in CFH antibody-negative patients (11% versus 38%) and than in non-exclusively pediatric CFH antibody-positive population (37).…”

“…Few descriptive reports on clinical and biologic data and treatments for CFH antibody-positive aHUS have been published (25,26,(29)(30)(31)(32)(33)(35)(36)(37). This study sought to evaluate the frequency of deletions in the CFHR1-5 genes and the presence of CFH antibodies in pediatric patients with aHUS and in healthy blood donors.…”

The role of the alternative pathway of complement activation in glomerular diseases

“…3). In fact, autoantibodies to the C-terminal end of CFH are found in approximately 10% of aHUS patients, and the majority of them have a homozygous deletion of CHFR1 [37,108,109]. Furthermore, the prevalence of anti-CFH antibodies correlates with the occurrence of CFHR3-1Δ variant, known to be protective against IgAN and AMD, and a risk factor for SLE and aHUS [47,70,83].…”