The shared CTLA4-ICOS risk locus in celiac disease, IgA deficiency and common variable immunodeficiency

K. Haimila, E. Einarsdottir, A. de Kauwe, L. L E Koskinen, Q. Pan-Hammarström, T. Kaartinen, K. Kurppa, F. Ziberna, T. Not, S. Vatta, A. Ventura, I. R. Korponay-Szabo, R. Ádány, Z. Pocsai, G. Széles, E. Dukes, K. Kaukinen, M. Mäki, S. Koskinen, J. PartanenL. Hammarström, P. Saavalainen

Research output: Contribution to journalArticle

Abstract

IgA deficiency (IgAD) and common variable immunodeficiency (CVID) often co-occur in families, associating with chronic inflammatory diseases such as celiac disease (CD). ICOS (inducible co-stimulator) and CTLA4 (cytotoxic T-lymphocyte-associated protein-4) may be important in both disorders, as ICOS is necessary for Ig class-switching and CTLA4 negatively regulates T-cell activation. Linkage and association of CD with CTLA4-ICOS is well documented, we thus aimed to further pinpoint CD susceptibility by haplotype-tagging analysis. We genotyped 663 CD families from Finland and Hungary, 575 additional CD patients from Finland, Hungary and Italy; 275 Swedish and Finnish IgAD individuals and 87 CVID individuals for 14-18 genetic markers in CTLA4-ICOS. Association was found between CTLA4-ICOS and both IgAD (P=0.0015) and CVID (P=0.0064). We confirmed linkage of CTLA4-ICOS with CD (LOD 2.38, P=0.0005) and found association of CTLA4-ICOS with CD (P=0.0009). Meta-analysis of the IgAD, CVID and CD materials revealed intergenic association (P=0.0005). Disease-associated markers were associated with lower ICOS and higher CTLA4 expression, indicating that the risk haplotypes contain functional variants. In summary, we identified a novel shared risk locus for IgAD, CVID and CD, the first report of association between CTLA4-ICOS and IgAD. Association between CD and CTLA4-ICOS was also confirmed in a large European data set.

Original languageEnglish
Pages (from-to)151-161
Number of pages11
JournalGenes and Immunity
Volume10
Issue number2
DOIs
Publication statusPublished - 2009

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Inducible T-Cell Co-Stimulator Protein
IgA Deficiency
Common Variable Immunodeficiency
Celiac Disease
Cytotoxic T-Lymphocytes
Proteins
Hungary
Finland
Haplotypes
Immunoglobulin Class Switching
Disease Susceptibility
Genetic Markers
Italy
Meta-Analysis

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

Haimila, K., Einarsdottir, E., de Kauwe, A., Koskinen, L. L. E., Pan-Hammarström, Q., Kaartinen, T., ... Saavalainen, P. (2009). The shared CTLA4-ICOS risk locus in celiac disease, IgA deficiency and common variable immunodeficiency. Genes and Immunity, 10(2), 151-161. https://doi.org/10.1038/gene.2008.89

The shared CTLA4-ICOS risk locus in celiac disease, IgA deficiency and common variable immunodeficiency. / Haimila, K.; Einarsdottir, E.; de Kauwe, A.; Koskinen, L. L E; Pan-Hammarström, Q.; Kaartinen, T.; Kurppa, K.; Ziberna, F.; Not, T.; Vatta, S.; Ventura, A.; Korponay-Szabo, I. R.; Ádány, R.; Pocsai, Z.; Széles, G.; Dukes, E.; Kaukinen, K.; Mäki, M.; Koskinen, S.; Partanen, J.; Hammarström, L.; Saavalainen, P.

In: Genes and Immunity, Vol. 10, No. 2, 2009, p. 151-161.

Research output: Contribution to journalArticle

Haimila, K, Einarsdottir, E, de Kauwe, A, Koskinen, LLE, Pan-Hammarström, Q, Kaartinen, T, Kurppa, K, Ziberna, F, Not, T, Vatta, S, Ventura, A, Korponay-Szabo, IR, Ádány, R, Pocsai, Z, Széles, G, Dukes, E, Kaukinen, K, Mäki, M, Koskinen, S, Partanen, J, Hammarström, L & Saavalainen, P 2009, 'The shared CTLA4-ICOS risk locus in celiac disease, IgA deficiency and common variable immunodeficiency', Genes and Immunity, vol. 10, no. 2, pp. 151-161. https://doi.org/10.1038/gene.2008.89
Haimila K, Einarsdottir E, de Kauwe A, Koskinen LLE, Pan-Hammarström Q, Kaartinen T et al. The shared CTLA4-ICOS risk locus in celiac disease, IgA deficiency and common variable immunodeficiency. Genes and Immunity. 2009;10(2):151-161. https://doi.org/10.1038/gene.2008.89
Haimila, K. ; Einarsdottir, E. ; de Kauwe, A. ; Koskinen, L. L E ; Pan-Hammarström, Q. ; Kaartinen, T. ; Kurppa, K. ; Ziberna, F. ; Not, T. ; Vatta, S. ; Ventura, A. ; Korponay-Szabo, I. R. ; Ádány, R. ; Pocsai, Z. ; Széles, G. ; Dukes, E. ; Kaukinen, K. ; Mäki, M. ; Koskinen, S. ; Partanen, J. ; Hammarström, L. ; Saavalainen, P. / The shared CTLA4-ICOS risk locus in celiac disease, IgA deficiency and common variable immunodeficiency. In: Genes and Immunity. 2009 ; Vol. 10, No. 2. pp. 151-161.
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AU - Haimila, K.

AU - Einarsdottir, E.

AU - de Kauwe, A.

AU - Koskinen, L. L E

AU - Pan-Hammarström, Q.

AU - Kaartinen, T.

AU - Kurppa, K.

AU - Ziberna, F.

AU - Not, T.

AU - Vatta, S.

AU - Ventura, A.

AU - Korponay-Szabo, I. R.

AU - Ádány, R.

AU - Pocsai, Z.

AU - Széles, G.

AU - Dukes, E.

AU - Kaukinen, K.

AU - Mäki, M.

AU - Koskinen, S.

AU - Partanen, J.

AU - Hammarström, L.

AU - Saavalainen, P.

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