Клинические особенности течения и исходы атипичного гемолитико-уремического синдрома, ассоциированного с антителами к Фактору H

Abstract

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).