The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Emma Ahlqvist

Emma Ahlqvist

Assistant researcher

Emma Ahlqvist

Mutations in genes encoding complement inhibitors CD46 and CFH affect the age at nephritis onset in patients with systemic lupus erythematosus

Author

  • Andreas Jönsen
  • Sara Nilsson
  • Emma Ahlqvist
  • Elisabet Svenungsson
  • Iva Gunnarsson
  • Karin G. Eriksson
  • Anders Bengtsson
  • Agneta Zickert
  • Maija-Leena Eloranta
  • Lennart Truedsson
  • Lars Ronnblom
  • Gunnel Nordmark
  • Gunnar Sturfelt
  • Anna Blom

Summary, in English

Introduction: Inherited deficiencies of several complement components strongly predispose to systemic lupus erythematosus (SLE) while deficiencies of complement inhibitors are found in kidney diseases such as atypical hemolytic uremic syndrome (aHUS). Methods: The exons of complement inhibitor genes CD46 and CFH (factor H) were fully sequenced using the Sanger method in SLE patients with nephritis originating from two cohorts from southern and mid Sweden (n = 196). All identified mutations and polymorphisms were then analyzed in SLE patients without nephritis (n = 326) and in healthy controls (n = 523). Results: We found nonsynonymous, heterozygous mutations in CFH in 6.1% patients with nephritis, in comparison with 4.0% and 5.4% in patients without nephritis and controls, respectively. No associations of SLE or nephritis with common variants in CFH (V62I/Y402H/E936D) were found. Furthermore, we found two nonsynonymous heterozygous mutations in CD46 in SLE patients but not in controls. The A353V polymorphism, known to affect function of CD46, was found in 6.6% of nephritis patients versus 4.9% and 6.1% of the non-nephritis SLE patients and controls. The presence of mutations in CD46 and CFH did not predispose to SLE or nephritis but was associated with earlier onset of nephritis. Furthermore, we found weak indications that there is one protective and one risk haplotype predisposing to nephritis composed of several polymorphisms in noncoding regions of CD46, which were previously implicated in aHUS. Conclusions: SLE nephritis is not associated with frequent mutations in CFH and CD46 as found in aHUS but these may be modifying factors causing earlier onset of nephritis.

Department/s

  • Rheumatology
  • Protein Chemistry, Malmö
  • Genomics, Diabetes and Endocrinology
  • Division of Microbiology, Immunology and Glycobiology - MIG
  • EpiHealth: Epidemiology for Health

Publishing year

2011

Language

English

Publication/Series

Arthritis Research and Therapy

Volume

13

Issue

6

Document type

Journal article

Publisher

BioMed Central (BMC)

Topic

  • Rheumatology and Autoimmunity

Status

Published

Research group

  • Protein Chemistry, Malmö
  • Genomics, Diabetes and Endocrinology

ISBN/ISSN/Other

  • ISSN: 1478-6362