Factor H autoantibody is associated with atypical hemolytic uremic syndrome in children in the United Kingdom and Ireland

Abstract

Factor H autoantibodies can impair complement regulation, resulting in atypical hemolytic uremic syndrome, predominantly in childhood. There are no trials investigating treatment, and clinical practice is only informed by retrospective cohort analysis. Here we examined 175 children presenting with atypical hemolytic uremic syndrome in the United Kingdom and Ireland for factor H autoantibodies that included 17 children with titers above the international standard. Of the 17, seven had a concomitant rare genetic variant in a gene encoding a complement pathway component or regulator. Two children received supportive treatment; both developed established renal failure. Plasma exchange was associated with a poor rate of renal recovery in seven of 11 treated. Six patients treated with eculizumab recovered renal function. Contrary to global practice, immunosuppressive therapy to prevent relapse in plasma exchange–treated patients was not adopted due to concerns over treatment-associated complications. Without immunosuppression, the relapse rate was high (five of seven). However, reintroduction of treatment resulted in recovery of renal function. All patients treated with eculizumab achieved sustained remission. Five patients received renal transplants without specific factor H autoantibody–targeted treatment with recurrence in one who also had a functionally significant CFI mutation. Thus, our current practice is to initiate eculizumab therapy for treatment of factor H autoantibody–mediated atypical hemolytic uremic syndrome rather than plasma exchange with or without immunosuppression. Based on this retrospective analysis we see no suggestion of inferior treatment, albeit the strength of our conclusions is limited by the small sample size.

Thrombotic Microangiopathy and the Kidney

“…There is a strong association with homozygous deletion of CFHR3 and CFHR1, which encode the proteins FHR3 and FHR1 (21), although the mechanism is not understood; CFHR3/1 deletion is a common polymorphism, and it is not present in all individuals who develop FH autoantibodies (22). It predominantly presents in childhood, frequently with a gastrointestinal prodrome.…”

Atypical Hemolytic Uremic Syndrome in a 13-year-old Lao Girl: A Case Report

“…The prevalence of antiCFHaHUS shows ethnic differences. However, pre valence in studies reporting exclusively pediatric cases (10-56% of total cases with aHUS) 2,911) is higher than that www.chikd.org in studies reporting both, pediatric and adult cases (5-10 %) 3,11,12) . A large cohort study that included patients with antiCFHaHUS 6) reported that abnormal activation of the alternative complement pathway (low serum C3 levels with normal C4 levels) was observed in 58% of the patients at disease onset, as was observed in our patient.…”

Long-term outcomes and response to treatment in diacylglycerol kinase epsilon nephropathy

“…Patient identification numbers were allocated according to time of referral to our center; they begin at NCL25 to maintain consistency with our previously published study on factor H autoantibody-associated aHUS. 27 Six patients had a renal biopsy (NCL25, NCL26, NCL27, NCL29, NCL34, and NCL37).…”