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.

Figure 1.

Anti-FH associated-aHUS occurs mainly in late childhood but can affect adults.

Figure 2.

At onset, the majority of patients shows complement alternative pathway activation (decreased C3 and/or Factor B) and a subset has decreased FH. The dashed lines represent the lower limit of normal range (for C3, FB, and FH antigenic levels) or the positive threshold (for anti-FH IgG titers).

Figure 3.

Anti-FH levels are lower at remission than at disease onset. The difference reaches statistical significance using the t test.

Figure 4.

Low C3 levels at onset are correlated with a higher risk of disease relapse. The Kaplan-Meier curves calculate the probability of survival without relapse and of renal survival (ESRD or death) according to C3 levels at onset (normal or low levels) and the disease progression parameters of 31 patients from our series of anti-FH–associated aHUS.