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. 2012 Oct;64(10):3383-7.
doi: 10.1002/art.34571.

Brief Report: IRF5 systemic lupus erythematosus risk haplotype is associated with asymptomatic serologic autoimmunity and progression to clinical autoimmunity in mothers of children with neonatal lupus

Tharian S Cherian  1 , Silvia N Kariuki, Beverly S Franek, Jill P Buyon, Robert M Clancy, Timothy B Niewold
Affiliations

Brief Report: IRF5 systemic lupus erythematosus risk haplotype is associated with asymptomatic serologic autoimmunity and progression to clinical autoimmunity in mothers of children with neonatal lupus

Tharian S Cherian et al. Arthritis Rheum. 2012 Oct.

Abstract

Objective: Variation in the interferon regulatory factor 5 (IRF5) gene has been associated with risk of developing systemic lupus erythematosus (SLE), and this association is largely dependent upon anti-Ro autoantibodies. This study was undertaken to determine if the IRF5 genotype is associated with maternal diagnosis or progression of autoimmunity.

Methods: Genotyping of haplotype-tagging polymorphisms in IRF5 was performed in 93 subjects of European ancestry who were recruited to the Research Registry for Neonatal Lupus. All subjects had high-titer anti-Ro autoantibodies and had a child with neonatal lupus (NL); allele frequencies were compared to those in nonautoimmune controls. The mothers had SLE, Sjögren's syndrome (SS), or undifferentiated autoimmune syndrome (UAS), or were asymptomatic.

Results: The SLE risk haplotype of IRF5 was enriched in all anti-Ro-positive subjects except in those with SS (odds ratio [OR] 2.55, P = 8.8 × 10(-4) ). The SLE risk haplotype was even enriched in asymptomatic individuals with anti-Ro antibodies (OR 2.69, P = 0.019). The same haplotype was more prevalent in subjects who were initially asymptomatic but developed symptomatic SLE during followup (OR 5.83, P = 0.0024). Interestingly, SS was associated with 2 minor IRF5 haplotypes, and these same haplotypes were decreased in frequency in mothers with SLE and those with UAS.

Conclusion: The IRF5 SLE risk haplotype was associated with anti-Ro antibody positivity in asymptomatic individuals, as well as with progression to SLE in asymptomatic anti-Ro-positive individuals. SS in mothers of children with NL was associated with different IRF5 haplotypes. These data suggest that IRF5 polymorphisms play a role in serologic autoimmunity in humans and may promote the progression to clinical autoimmunity.

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Conflict of interest statement

Financial Disclosures and Conflict of Interest: The authors report no financial conflict of interest.

Figures

Figure 1
Figure 1
IRF5 haplotype diagram and haplotype frequencies in the NL mothers. A. and B. show the pairwise correlations between SNPs as r-squared values for the NL mothers (A.) and controls (B.) respectively, with darker shading indicating a higher r-squared and thus a greater degree of correlation. C. and D. show the frequencies of the 5 major haplotypes observed in the NL mothers (C.) and controls (D.) respectively.
See this image and copyright information in PMC

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References

    1. Buyon JP, Hiebert R, Copel J, Craft J, Friedman D, Katholi M, et al. Autoimmune-associated congenital heart block: demographics, mortality, morbidity and recurrence rates obtained from a national neonatal lupus registry. J Am Coll Cardiol. 1998;31(7):1658–1666. - PubMed
    1. Rivera TL, Izmirly PM, Birnbaum BK, Byrne P, Brauth JB, Katholi M, et al. Disease progression in mothers of children enrolled in the Research Registry for Neonatal Lupus. Ann Rheum Dis. 2009;68(6):828–835. - PMC - PubMed
    1. Mavragani CP, Niewold TB, Moutsopoulos NM, Pillemer SR, Wahl SM, Crow MK. Augmented interferon-alpha pathway activation in patients with Sjogren's syndrome treated with etanercept. Arthritis Rheum. 2007;56(12):3995–4004. - PMC - PubMed
    1. Weckerle CE, Franek BS, Kelly JA, Kumabe M, Mikolaitis RA, Green SL, et al. Network analysis of associations between serum interferon-alpha activity, autoantibodies, and clinical features in systemic lupus erythematosus. Arthritis Rheum. 2011;63(4):1044–1053. - PMC - PubMed
    1. Niewold TB, Rivera TL, Buyon JP, Crow MK. Serum type I interferon activity is dependent on maternal diagnosis in anti-SSA/Ro-positive mothers of children with neonatal lupus. Arthritis Rheum. 2008;58(2):541–546. - PMC - PubMed

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