Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Association of multiple sclerosis with ILT6 deficiency

Genes & Immunity volume 6, pages 445–447 (2005)Cite this article

Abstract

Multiple sclerosis (MS) is an autoimmune disorder of multifactorial etiology. Family studies have shown strong genetic contributions. Linkage analyses have revealed several regions harboring risk genes including chromosome region 19q13. ILT6 is one of the most interesting candidate genes, since ILTs are involved in the generation of immunological tolerance. There is an absence/presence of variability of the ILT6 gene comprising several exons, thus incapacitating the gene function. In the present study, we examined the association of ILT6 deletion with MS. Using PCR typing, deficiency of ILT6 was examined in 607 blood donors and in 751 Caucasian German, as well as 89 French MS patients. Homozygous ILT6 deficiencies were significantly more prevalent in MS patients (7.1%) than in blood donors (3.8%; P=0.009). ILT6 deficiency is associated with MS in the German population and hence a likely risk factor for autoimmune disorders.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. Robertson NP, Clayton D, Fraser M, Deans J, Compston DA . Clinical concordance in sibling pairs with multiple sclerosis. Neurology 1996; 47: 347–352.

    Article  CAS  Google Scholar 

  2. Ebers GC, Sadovnick AD, Risch NJ . A genetic basis for familial aggregation in multiple sclerosis. Canadian Collaborative Study Group. Nature 1995; 377: 150–151.

    CAS  Google Scholar 

  3. Ebers GC, Bulman DE, Sadovnick AD et al. A population-based study of multiple sclerosis in twins. N Engl J Med 1986; 315: 1638–1642.

    Article  CAS  Google Scholar 

  4. Barcellos LF, Thomson G, Carrington M et al. Chromosome 19 single-locus and multilocus haplotype associations with multiple sclerosis. Evidence of a new susceptibility locus in Caucasian and Chinese patients. JAMA 1997; 278: 1256–1261.

    Article  CAS  Google Scholar 

  5. Pericak-Vance MA, Rimmler JB, Martin ER et al. Linkage and association analysis of chromosome 19q13 in multiple sclerosis. Neurogenetics 2001; 3: 195–201.

    Article  CAS  Google Scholar 

  6. Haines JL, Bradford Y, Garcia ME et al. The Multiple Sclerosis Genetics Group. Multiple susceptibility loci for multiple sclerosis. Hum Mol Genet 2002; 11: 2251.

    Article  CAS  Google Scholar 

  7. Young NT, Canavez F, Uhrberg M, Shum BP, Parham P . Conserved organization of the ILT/LIR gene family within the polymorphic human leukocyte receptor complex. Immunogenetics 2001; 53: 270–278.

    Article  CAS  Google Scholar 

  8. Trowsdale J, Barten R, Haude A, Stewart CA, Beck S, Wilson MJ . The genomic context of natural killer receptor extended gene families. Immunol Rev 2001; 181: 20–38.

    Article  CAS  Google Scholar 

  9. Colonna M, Navarro F, Bellon T et al. A common inhibitory receptor for major histocompatibility complex class I molecules on human lymphoid and myelomonocytic cells. J Exp Med 1997; 186: 1809–1818.

    Article  CAS  Google Scholar 

  10. Shiroishi M, Tsumoto K, Amano K et al. Human inhibitory receptors Ig-like transcript 2 (ILT2) and ILT4 compete with CD8 for MHC class I binding and bind preferentially to HLA-G. Proc Natl Acad Sci USA 2003; 100: 8856–8861.

    Article  CAS  Google Scholar 

  11. Dietrich J, Cella M, Colonna M . Ig-like transcript 2 (ILT2)/leukocyte Ig-like receptor 1 (LIR1) inhibits TCR signaling and actin cytoskeleton reorganization. J Immunol 2001; 166: 2514–2521.

    Article  CAS  Google Scholar 

  12. Chang CC, Ciubotariu R, Manavalan JS et al. Tolerization of dendritic cells by T (S) cells: the crucial role of inhibitory receptors ILT3 and ILT4. Nat Immunol 2002; 3: 237–243.

    Article  CAS  Google Scholar 

  13. Torkar M, Haude A, Milne S, Beck S, Trowsdale J, Wilson MJ . Arrangement of the ILT gene cluster: a common null allele of the ILT6 gene results from a 6.7-kbp deletion. Eur J Immunol 2000; 30: 3655–3662.

    Article  CAS  Google Scholar 

  14. Kubagawa H, Cooper MD, Chen CC et al. Paired immunoglobulin-like receptors of activating and inhibitory types. Curr Top Microbiol Immunol 1999; 244: 137–149.

    CAS  Google Scholar 

  15. Ujike A, Takeda K, Nakamura A, Ebihara S, Akiyama K, Takai T . Impaired dendritic cell maturation and increased T(H)2 responses in PIR-B-(−/−)mice. Nat Immunol 2002; 3: 542–548.

    Article  CAS  Google Scholar 

  16. Borges L, Hsu ML, Fanger N, Kubin M, Cosman D . A family of human lymphoid and myeloid Ig-like receptors, some of which bind to MHC class I molecules. J Immunol 1997; 159: 5192–5196.

    CAS  PubMed  Google Scholar 

  17. Norman PJ, Carey BS, Stephens HA, Vaughan RW . DNA sequence variation and molecular genotyping of natural killer leukocyte immunoglobulin-like receptor, LILRA3. Immunogenetics 2003; 55: 165–171.

    Article  CAS  Google Scholar 

  18. Miterski B, Bohringer S, Klein W et al. Inhibitors in the NFkappaB cascade comprise prime candidate genes predisposing to multiple sclerosis, especially in selected combinations. Genes Immun 2002; 3: 211–219.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by Kompetenznetz Rheuma grant C2.12.

Author information

Author notes

  1. S Koch and R Goedde: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Clinical Immunology, Medical School, Hannover, Germany

    S Koch, T Momot, R E Schmidt & T Witte

  2. Department of Human Genetics, Ruhr-University, Bochum, Germany

    R Goedde, V Nigmatova & J T Epplen

  3. Department of Medicine, University of Essen, Essen, Germany

    N Müller

  4. Department of Neurology, University of Lille, Lille, France

    J de Seze & P Vermersch

Authors
  1. S Koch
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R Goedde
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. V Nigmatova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J T Epplen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. N Müller
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J de Seze
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. P Vermersch
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. T Momot
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. R E Schmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. T Witte
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T Witte.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Koch, S., Goedde, R., Nigmatova, V. et al. Association of multiple sclerosis with ILT6 deficiency. Genes Immun 6, 445–447 (2005). https://doi.org/10.1038/sj.gene.6364187

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gene.6364187

Keywords

This article is cited by

Search

Advanced search

Quick links