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 (FHR1 and FHR3) (FHR1/3 ). We now report that Indian paediatric aHUS patients without anti-FH autoantibodies also showed modestly higher frequencies of the FHR1/3 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 (SCRs) 17-20 with higher binding avidities than for native FH. FH SCR17-20-binding anti-FH autoantibodies also bound the other cell-surface anchoring polyanionic binding site-containing region FH SCR5-8, 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 FHR1/3 genotype. Our data suggest a complex matrix of interactions between FHR1-FHR3 deletion, immunomodulation and anti-FH autoantibodies in the aetiopathogenesis of aHUS.