Genetic variation near IRF8 is associated with serologic and cytokine profiles in systemic lupus erythematosus and multiple sclerosis

B. S. Chrabot, S. N. Kariuki, M. I. Zervou, X. Feng, J. Arrington, M. Jolly, D. T. Boumpas, A. T. Reder, G. N. Goulielmos, T. B. Niewold

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29 Citations (Scopus)

Abstract

Alleles of interferon (IFN) regulatory factor 8 (IRF8) are associated with susceptibility to both systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Although high-type I IFN is thought to be causal in SLE, type I IFN is used as a therapy in MS. We investigated whether IRF8 alleles were associated with type I IFN levels or serologic profiles in SLE and MS. Alleles that have been previously associated with SLE or MS were genotyped in SLE and MS patients. The MS-associated rs17445836G allele was associated with anti-double-stranded DNA (dsDNA) autoantibodies in SLE patients (meta-analysis odds ratio=1.92). The same allele was associated with decreased serum IFN activity in SLE patients with anti-dsDNA antibodies, and with decreased type I IFN-induced gene expression in peripheral blood mononuclear cell from anti-dsDNA-negative SLE patients. In secondary progressive MS patients, rs17445836G was associated with decreased serum type I IFN. Rs17445836G was associated with increased IRF8 expression in SLE patient B cells. In summary, IRF8 rs17445836G is associated with human autoimmune disease characterized by low-type I IFN levels, and this may have pharmacogenetic relevance as type I IFN is modulated in SLE and MS. The association with autoantibodies and increased IRF8 expression in B cells supports a role for rs17445836G in humoral tolerance.

Original languageEnglish (US)
Pages (from-to)471-478
Number of pages8
JournalGenes and Immunity
Volume14
Issue number8
DOIs
StatePublished - Dec 2013

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Systemic Lupus Erythematosus
Multiple Sclerosis
Interferon Type I
Cytokines
Alleles
Autoantibodies
B-Lymphocytes
Chronic Progressive Multiple Sclerosis
Pharmacogenetics
DNA
Serum
Interferons
Autoimmune Diseases
Meta-Analysis
Blood Cells
Odds Ratio
Gene Expression
Antibodies

Keywords

  • autoantibodies
  • interferon regulatory factors
  • systemic lupus erythematosus
  • type I interferon

ASJC Scopus subject areas

  • Genetics(clinical)
  • Immunology
  • Genetics

Cite this

Chrabot, B. S., Kariuki, S. N., Zervou, M. I., Feng, X., Arrington, J., Jolly, M., ... Niewold, T. B. (2013). Genetic variation near IRF8 is associated with serologic and cytokine profiles in systemic lupus erythematosus and multiple sclerosis. Genes and Immunity, 14(8), 471-478. https://doi.org/10.1038/gene.2013.42

Genetic variation near IRF8 is associated with serologic and cytokine profiles in systemic lupus erythematosus and multiple sclerosis. / Chrabot, B. S.; Kariuki, S. N.; Zervou, M. I.; Feng, X.; Arrington, J.; Jolly, M.; Boumpas, D. T.; Reder, A. T.; Goulielmos, G. N.; Niewold, T. B.

In: Genes and Immunity, Vol. 14, No. 8, 12.2013, p. 471-478.

Research output: Contribution to journalArticle

Chrabot, BS, Kariuki, SN, Zervou, MI, Feng, X, Arrington, J, Jolly, M, Boumpas, DT, Reder, AT, Goulielmos, GN & Niewold, TB 2013, 'Genetic variation near IRF8 is associated with serologic and cytokine profiles in systemic lupus erythematosus and multiple sclerosis', Genes and Immunity, vol. 14, no. 8, pp. 471-478. https://doi.org/10.1038/gene.2013.42
Chrabot, B. S. ; Kariuki, S. N. ; Zervou, M. I. ; Feng, X. ; Arrington, J. ; Jolly, M. ; Boumpas, D. T. ; Reder, A. T. ; Goulielmos, G. N. ; Niewold, T. B. / Genetic variation near IRF8 is associated with serologic and cytokine profiles in systemic lupus erythematosus and multiple sclerosis. In: Genes and Immunity. 2013 ; Vol. 14, No. 8. pp. 471-478.
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abstract = "Alleles of interferon (IFN) regulatory factor 8 (IRF8) are associated with susceptibility to both systemic lupus erythematosus (SLE) and multiple sclerosis (MS). Although high-type I IFN is thought to be causal in SLE, type I IFN is used as a therapy in MS. We investigated whether IRF8 alleles were associated with type I IFN levels or serologic profiles in SLE and MS. Alleles that have been previously associated with SLE or MS were genotyped in SLE and MS patients. The MS-associated rs17445836G allele was associated with anti-double-stranded DNA (dsDNA) autoantibodies in SLE patients (meta-analysis odds ratio=1.92). The same allele was associated with decreased serum IFN activity in SLE patients with anti-dsDNA antibodies, and with decreased type I IFN-induced gene expression in peripheral blood mononuclear cell from anti-dsDNA-negative SLE patients. In secondary progressive MS patients, rs17445836G was associated with decreased serum type I IFN. Rs17445836G was associated with increased IRF8 expression in SLE patient B cells. In summary, IRF8 rs17445836G is associated with human autoimmune disease characterized by low-type I IFN levels, and this may have pharmacogenetic relevance as type I IFN is modulated in SLE and MS. The association with autoantibodies and increased IRF8 expression in B cells supports a role for rs17445836G in humoral tolerance.",
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