Puraswani, Mamta and Khandelwal, Priyanka and Saini, Himanshi and Saini, Savita and Gurjar, Bahadur Singh and Sinha, Aditi and Shende, Rajashri Pramod and Maiti, Tushar Kanti and Singh, Abhishek Kumar and Kanga, Uma and Ali, Uma and Agarwal, Indira and Anand, Kanav and Prasad, Narayan and Rajendran, Padmaraj and Sinha, Rajiv and Vasudevan, Anil and Saxena, Anita and Agarwal, Sanjay and Hari, Pankaj and Sahu, Arvind and Rath, Satyajit and Bagga, Arvind (2019) Clinical and Immunological Profile of Anti-factor H Antibody Associated Atypical Hemolytic Uremic Syndrome: A Nationwide Database. Frontiers in Immunology, 10. ISSN 1664-3224

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Abstract

Hemolytic uremic syndrome (HUS) is an important cause of acute kidney injury (AKI) in children (1, 2). While the majority of patients follow gastrointestinal infection with Shiga toxin associated organisms, abnormalities in the complement and coagulation pathways are associated with atypical hemolytic uremic syndrome (aHUS) (1, 3). Although 5–25% patients in European cohorts show antibodies to factor H (FH) (4– 6), this subset of illness is common in India accounting for ∼50% cases (7). Recent data from the global aHUS registry, from centers in Europe, North America and Australia, confirm the presence of anti-FH antibodies in 24% children and 19% adults (8). The pathogenesis of anti-FH associated aHUS and reasons for its high frequency in south Asia are unclear. While more than 80% patients show a homozygous deletion in the gene encoding FH related protein 1 (CFHR1), the deletion is present in 5– 10% healthy people across the world. High levels of antibodies at disease onset or relapse are believed to induce functional deficiency of FH; their decline in response to plasmapheresis is associated with disease remission (7, 9, 10). The antibodies bind chiefly to the C-terminus of FH, inhibiting its cell surface regulatory functions (11, 12). A dose-response relationship is not established as many patients show high antibody levels even during remission, emphasizing the need to evaluate other markers of complement activation. Studies relating antibody titers to functional assays of FH inhibition, such as level of sheep red blood cell (SRBC) lysis, free FH, soluble terminal complement complex (sC5b-9) and epitope specificity of antibodies are limited (9, 13, 14). We report the clinical features and outcomes of a large nationwide database of patients with anti-FH associated HUS. We also examined the functional implications of anti-FH antibodies and biomarkers that might enable prediction of a relapse.

Item Type:	Article
Subjects:	Biochemical and Biophysical Sciences
Depositing User:	RCB Library
Date Deposited:	25 Jun 2020 07:41
Last Modified:	25 Jun 2020 07:41
URI:	http://rcb.sciencecentral.in/id/eprint/278

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