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Immunology. 2018 Feb 27. doi: 10.1111/imm.12916. [Epub ahead of print]

Characterization of genetic predisposition and autoantibody profile in atypical haemolytic-uraemic syndrome.

Author information

1
National Institute of Immunology, New Delhi, India.
2
National Centre for Cell Science, S. P. Pune University Campus, Pune, India.
3
Regional Centre for Biotechnology, Faridabad, India.
4
Department of Biotechnology, Manipal Academy of Higher Education, Manipal, India.
5
Paediatric Biology Centre, Translational Health Science and Technology Institute, Faridabad, India.
6
Department of Paediatrics, All India Institute of Medical Sciences, New Delhi, India.
7
Kirori Mal College, University of Delhi, Delhi, India.
8
Agharkar Research Institute, Pune, India.

Abstract

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.

KEYWORDS:

complement factor H autoantibodies; genetic predisposition to autoimmunity; haemolytic-uraemic syndrome

PMID:
29485195
PMCID:
PMC6050217
[Available on 2019-08-01]
DOI:
10.1111/imm.12916
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