Atypical hemolytic-uremic syndrome associated with antibodies to factor H
Authors:   Moscow State Medical and Dental University, Moscow, Russia, Emirova Kh.M. ,   Saint Vladimir Moscow City Children's Clinical Hospital, Moscow, Russia, Pankratenko T.E. ,   Saint Vladimir Moscow City Children's Clinical Hospital, Moscow, Russia,   M.F. Vladimirsky Moscow Oblast Regional Scientific and Research Clinical Institute (MONIKI), Moscow, Russia, Vakhitov V.K. ,   Kazan State Medical University, Kazan, Republic of Tatarstan, Russia, Orlova O.M. ,   Moscow State Medical and Dental University, Moscow, Russia,   Saint Vladimir Moscow City Children's Clinical Hospital, Moscow, Russia, Chernysheva O.O. ,   Moscow State Medical and Dental University, Moscow, Russia, Muzurov A.L. ,   Saint Vladimir Moscow City Children's Clinical Hospital, Moscow, Russia,   Russian Medical Academy for Continuous Professional Education, Moscow, Russia, Kudlay D.A. ,   I.M. Sechenov First Moscow State Medical University, Moscow, Russia,   M.V. Lomonosov Moscow State University, Moscow, Russia,   National Research Center Institute of Immunology of the Russian Federal Biomedical Agency, Moscow, Russia, Zaitseva O.V. ,   Moscow State Medical and Dental University, Moscow, Russia, Mstislavskaya S.A. ,   Moscow State Medical and Dental University, Moscow, Russia,   Saint Vladimir Moscow City Children's Clinical Hospital, Moscow, Russia, Abaseeva T.Y. ,   Moscow State Medical and Dental University, Moscow, Russia,   Saint Vladimir Moscow City Children's Clinical Hospital, Moscow, Russia, Generalova G.A. ,   Saint Vladimir Moscow City Children's Clinical Hospital, Moscow, Russia,   Russian Medical Academy for Continuous Professional Education, Moscow, Russia, Shatalov P.A. ,   National Medical Radiology Research Center, Obninsk, Kaluga Oblast, Russia, Avdonin P.V. ,   Koltzov Institute of Developmental Biology of the Russian Academy of Sciences (IDB RAS), Moscow, Russia, Avdonin P.P. ,   Koltzov Institute of Developmental Biology of the Russian Academy of Sciences (IDB RAS), Moscow, Russia
Published: February 2024

Atypical hemolytic-uremic syndrome (aHUS) is an ultra-rare life-threatening disease from the group of thrombotic microangiopathies (TMA) with genetic predisposition factors associated with uncontrolled activation of the alternative complement pathway. In 10% of cases aHUS is acquired and associated with antibodies to factor H (CFH-Ab-aHUS), among which 90% of cases are also determined by a deficiency of plasma proteins related to factor H (CFHR). Information on the course, therapeutic approaches and outcomes of CFH-Ab-aHUS varies Worldwide and is presented by series of clinical observations. The purpose of the research was to determine the patterns of the course and outcomes of CFH-Ab-aHUS to substantiate methods of effective treatment and improve prognosis. Methods used: retro- and prospective analysis of the course and outcomes of CFH-Ab-aHUS in 43 patients in Jan. 2010-Feb. 2022. The sample is continuous. In the development of microangiopathic hemolytic anemia (MAHA), thrombocytopenia and acute kidney injury (AKI), the diagnosis of CFH-Ab-aHUS was established after exclusion of other forms of TMAs and determination of immunoglobulin class G (IgG) in serum against factor H by enzyme-linked immunosorbent assay (ELISA-VIDITEST anti-complement factor H, Czech Republic). In 41 cases molecular genetic study by NGS (next generation sequencing) for aHUS panel and Sanger sequencing were performed. Results: the incidence of CFH-Ab-aHUS was 20.6% among all cases of aHUS. In 88.4% of children the disease debuted at the age of above 4 y/o. It was associated with a trigger (infections, vaccination, trauma, etc.) in 76.7% of cases. The median (Me) level of antibodies to factor H was 12400 [4187; 22181] AU/ml, which was more than 8 times higher than the normal upper limit. The acute period was characterized by the development of the TMA triad (MAGA, thrombocytopenia, AKI) in 100%, hemorrhagic syndrome (69.8%), arterial hypertension (69.8%), C3 consumption (77.8%) and dysfunction of more than 2 systems (83.7%). Neoliguric form of AKI was diagnosed in 44.2%, cardiac involvement in 65.1%, CNS in 55.8%, GI in 51.2%, pulmonary in 23.3%, and visual organ in 16.3% of cases. CFHR1/CFHR3 deletions were found in 87.8% (36/41) of cases (77.8% homozygous/ 22.2% heterozygous). Relapses were noted in 34.9%. Remission of CFH-Ab-aHUS was achieved in 11.6% of cases using plasma therapy and immunosuppressants, in 88.4% - with complement-blocking therapy (eculizumab). The outcome of the disease was characterized by the development of arterial hypertension (65.1%), CKD (60.5%), hypertrophic (25.6%) and dilated cardiomyopathy (16.3%). Conclusion: thus, in the Russin pediatric population with aHUS, every fifth child is diagnosed with CFH-Ab-aHUS associated with a risk of recurrence in every third child. The most important components of the management of patients with CFH-Ab-aHUS are its timely diagnosis and initiation of pathogenetic therapy (plasma therapy with immunosuppressants/eculizumab).