Premium
Characterization of genetic predisposition and autoantibody profile in atypical haemolytic–uraemic syndrome
Author(s) -
Gurjar Bahadur Singh,
Manikanta Sriharsha Tholu,
Bhasym Angika,
Prabhu Savit,
Puraswani Mamta,
Khandelwal Priyanka,
Saini Himanshi,
Saini Savita,
Verma Anita Kamra,
Chatterjee Priyadarshini,
Guchhait Prasenjit,
Bal Vineeta,
George Anna,
Rath Satyajit,
Sahu Arvind,
Sharma Amita,
Hari Pankaj,
Sinha Aditi,
Bagga Arvind
Publication year - 2018
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12916
Subject(s) - autoantibody , epitope , immunology , antibody , genotype , medicine , genetics , biology , gene
Summary We previously reported that Indian paediatric patients with atypical haemolytic–uraemic syndrome ( aHUS ) showed high frequencies of anti‐complement factor H ( FH ) autoantibodies that are correlated with homozygous deletion of the genes for FH ‐related proteins 1 and 3 ( FHR 1 and FHR 3) ( FHR 1/3 –/– ). We now report that Indian paediatric aHUS patients without anti‐ FH autoantibodies also showed modestly higher frequencies of the FHR 1/3 –/– genotype. Further, when we characterized epitope specificities and binding avidities of anti‐ FH autoantibodies in aHUS patients, most anti‐ FH autoantibodies were directed towards the FH cell‐surface anchoring polyanionic binding site‐containing C‐terminal short conservative regions ( SCR s) 17–20 with higher binding avidities than for native FH . FH SCR 17–20‐binding anti‐ FH autoantibodies also bound the other cell‐surface anchoring polyanionic binding site‐containing region FH SCR 5–8, at lower binding avidities. Anti‐ FH autoantibody avidities correlated with antibody titres. These anti‐ FH autoantibody characteristics did not differ between aHUS patients with or without the FHR 1/3 –/– genotype. Our data suggest a complex matrix of interactions between FHR 1 ‐ FHR 3 deletion, immunomodulation and anti‐ FH autoantibodies in the aetiopathogenesis of aHUS .