Prompt plasma exchanges and immunosuppressive treatment improves the outcomes of anti-factor H autoantibody-associated hemolytic uremic syndrome in children

Abstract

Antibodies to complement factor H are an uncommon cause of hemolytic uremic syndrome (HUS). Information on clinical features and outcomes in children is limited. In order to explore this we studied a multicenter cohort of 138 Indian children with anti-complement factor H antibody associated HUS, constituting 56% of patients with HUS. Antibody titers were high (mean 7054 AU/ml) and correlated inversely with levels of complement C3, but not complement factor H. Homozygous deletion of the CFHR1 gene was found in 60 of 68 patients. Therapies included dialysis in 119 children, 105 receiving plasma exchanges and 26 intravenous immunoglobulin. Induction immunosuppression consisted of 87 children receiving prednisolone with or without intravenous cyclophosphamide or rituximab. Antibody titers fell significantly following plasma exchanges and increased during relapses. Adverse outcome (stage 4-5 CKD or death) was seen in 36 at 3 months and 41 by last follow up, with relapse in 14 of 122 available children. Significant independent risk factors for adverse outcome were an antibody titer over 8000 AU/ml, low C3 and delay in plasma exchange. Combined plasma exchanges and induction immunosuppression resulted in significantly improved renal survival: one adverse outcome prevented for every 2.6 patients treated. Maintenance immunosuppressive therapy, of prednisolone with either mycophenolate mofetil or azathioprine, significantly reduced the risk of relapses. Thus, prompt use of immunosuppressive agents and plasma exchanges are useful for improving outcomes in pediatric patients with anti-complement factor H-associated HUS.

Heterogeneity but individual constancy of epitopes, isotypes and avidity of factor H autoantibodies in atypical hemolytic uremic syndrome

“…Mutations in the factor H gene (CFH) are the most prevalent genetic alterations representing ~25% of cases ). In addition, autoantibodies directed to factor H (FH) are found in ~10% of aHUS cases, but larger proportions were also reported, depending on geographical region and ethnicity (Dragon-Durey et al 2005;Hofer, Giner, Jozsi 2014;Sinha et al 2014). This autoimmune form affects mainly children, and has a highly relapsing course with progression to ESRD ).…”

Complement factor H antibody-associated atypical hemolytic uremic syndrome and eculizumab treatment

“…Sinha ve ark. (10) , özellikle anti-FH antikorlarına bağlı aHÜS'te antikorların uzaklaştırılmasını sağladığı için plazma değişiminin yararlı olabileceğini ama antikorların immunsupresif tedavi ile de azaltılması gerektiğini bildirmişlerdir. Bir immunsupresif tedavi alternatifi olan anti CD20 antikoru olan Rituksimab, dirençli TTP hastalarında ya da anti-FH antikoru iliş-kili hastalarda kullanılmıştır (11) .…”

“…Anti-FH antikoru olan 138 aHUS tanılı hastada yapılan çalışmada, plazma değişimi ve oral prednizolon ve siklofosfamid ya da rituksimab tedavisini içeren immunsupresif tedavinin antikor düzeyini ortalama 32 günde azalttığı gösterilmiştir (10) . Bu tedavi ile hematolojik remisyonun sağlandığı ve klinik gidişin daha iyi olduğu gösterilmiştir (10) . Anti-FH antikoru olan aHUS tanılı hastalarda Ekulizumab kullanımı ile ilgili veriler oldukça sınırlı olmakla birlikte, etkisini gösteren yayınlar vardır (12,13) .…”

Egészségügyi szakmai irányelv – A thromboticus thrombocytopeniás purpura (TTP) és a haemolyticus uraemiás syndroma (HUS) kezeléséről

“…A kezelést úgy kell végezni, hogy az antitesttiter lehetőleg 1000 AU/ ml alá csökkenjen. A 8000 AU/ml feletti kiindulási antitesttiter kedvezőtlen prognózist sejtet [90]. Súlyos extrarenalis tünetek esetén (azonnali hatása miatt) az első vonalú eculizumab + immunszuppresszív kezelés lehet az optimális választás [91].…”