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:

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

Default user image.

Eero Lindholm

Associate professor

Default user image.

Variability in the CIITA gene interacts with HLA in multiple sclerosis.


  • A Gyllenberg
  • F Piehl
  • L Alfredsson
  • J Hillert
  • I L Bomfim
  • L Padyukov
  • Marju Orho-Melander
  • Eero Lindholm
  • Mona Landin-Olsson
  • Åke Lernmark
  • M Aili
  • L E Bååth
  • E Carlsson
  • H Edenwall
  • G Forsander
  • B W Granström
  • I Gustavsson
  • R Hanas
  • L Hellenberg
  • H Hellgren
  • E Holmberg
  • H Hörnell
  • Sten-A Ivarsson
  • C Johansson
  • G Jonsell
  • K Kockum
  • B Lindblad
  • A Lindh
  • J Ludvigsson
  • U Myrdal
  • Jan Neiderud
  • K Segnestam
  • S Sjö
  • L Skogsberg
  • L Strömberg
  • U Ståhle
  • B Thalme
  • K Tullus
  • T Tuvemo
  • M Wallensteen
  • O Westphal
  • J Aman
  • H Arnqvist
  • E Björck
  • J Eriksson
  • L Nyström
  • L O Ohlson
  • B Scherstén
  • J Ostman
  • T Olsson
  • I Kockum

Summary, in English

The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.Genes and Immunity advance online publication, 16 January 2014; doi:10.1038/gene.2013.71.


  • Diabetes - Cardiovascular Disease
  • Department of Clinical Sciences, Malmö
  • Medicine, Lund
  • Celiac Disease and Diabetes Unit
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year







Genes and Immunity





Document type

Journal article


Nature Publishing Group


  • Endocrinology and Diabetes



Research group

  • Diabetes - Cardiovascular Disease
  • Diabetes and Celiac Unit


  • ISSN: 1476-5470