Anti-factor H antibody and its role in atypical hemolytic uremic syndrome

Abstract

Atypical hemolytic uremic syndrome (aHUS) an important form of a thrombotic microangiopathy (TMA) that can frequently lead to acute kidney injury (AKI). An important subset of aHUS is the anti-factor H associated aHUS. This variant of aHUS can occur due to deletion of the complement factor H genes, CFHR1 and CFHR3, along with the presence of anti-factor H antibodies. However, it is a point of interest to note that not all patients with anti-factor H associated aHUS have a CFHR1/R3 deletion. Factor-H has a vital role in the regulation of the complement system, specifically the alternate pathway. Therefore, dysregulation of the complement system can lead to inflammatory or autoimmune diseases. Patients with this disease respond well to treatment with plasma exchange therapy along with Eculizumab and immunosuppressant therapy. Anti-factor H antibody associated aHUS has a certain genetic predilection therefore there is focus on further advancements in the diagnosis and management of this disease. In this article we discuss the baseline characteristics of patients with anti-factor H associated aHUS, their triggers, various treatment modalities and future perspectives.

Keywords: aHUS; anti-factor H antibody; atypical hemolytic uremic syndrome; factor H; pediatric.

Figure 1

FH is an important regulatory protein of the complement pathway, with its effect mainly on the alternate pathway of the complement system. FH regulates the complement system via two mechanisms: DAA and CA. DAA enables FH to displace Bb fragment of FB off C3 convertase. Thus, the accelerated irreversible decay of C3bBb into C3b and Bb takes place. In the CA mechanism, FH has the role of a facilitator in the FI-mediated cleavage of C3b to iC3b, which is an inactivated form of C3b. The green ‘+’ arrows exhibit stimulatory or enhanced action whereas red ‘-’ arrows exhibit inhibitory action. Thus, over-amplification of the complement pathway is regulated by FH. The C5b-9 is one of the terminal components of the MAC which mediates the cell lysis and activation completing the complement cascade. The broken arrow implies that MAC enhances the process of thrombus formation from platelets which consists of a series of steps. (FH-factor-H; FI-factor-I; FB-factor-B; FD-factor-D; MAC-membrane attack complex; DAA-decay accelerating activity; CA-co-factor activity; iC3b-inactivated C3b).