Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.


IRF8 Allele Associated with Susceptibility to Multiple Sclerosis Is Associated with Serum Interferon Alpha and Serologic Profile in Systemic Lupus Erythematosus.

Franek2,  Beverly S., Kariuki2,  Silvia N., Arrington2,  Jasmine, Mikolaitis3,  Rachel A., Jolly3,  Meenakshi, Utset2,  Tammy O., Boumpas1,  Dimitrios T.

Internal Medicine and Rheumatology, Clinical Immunology and Allergy, University of Crete Medical School, Heraklion, Greece
Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, University of Chicago
Section of Rheumatology, Rush University Medical Center

Objective:

Alleles of IRF8 have been associated with susceptibility to both systemic lupus erythematosus (SLE) and multiple sclerosis (MS). While interferon alpha (IFN-a) is thought to be causal in SLE, recombinant human IFN-a is used as a therapy in MS. We investigated whether the IRF8 alleles associated with these two diseases were associated with differences in serum IFN-a or serologic profile in a multi-ancestral cohort of SLE patients.

Methods:

The rs12444486 and rs17445836 single nucleotide polymorphisms (SNPs) in IRF8 (associated with SLE and MS respectively) were genotyped with Taqman primer-probe sets in 244 African-American and 137 European ancestry SLE patients. All patients had serum IFN-a and serology data available, and had been previously genotyped at SLE-risk SNPs in the IRF5 and IRF7 loci. Data from each ancestral background was analyzed separately initially, and combined in meta-analysis when associations were not significantly heterogeneous between ancestral backgrounds. Principal component analysis was used to control for proportional ancestry at the individual level.

Results:

The MS-associated rs17445836 G allele was associated with the presence of anti-dsDNA autoantibodies in SLE patients of both ancestral backgrounds [meta-analysis OR=2.01 (1.09–3.68), p=0.024]. The same allele was also associated with increased serum IFN-a activity in both ancestral backgrounds (meta-analysis p=0.017). There was no evidence for statistical interaction between rs17445836 G and SNPs in IRF5 and IRF7 which have been previously associated with anti-dsDNA in SLE patients. No significant associations were observed between the SLE-associated rs12444486 SNP and serum IFN-a or serologic profile.

Conclusions:

The rs17445836 G allele associated with susceptibility to MS was associated with anti-dsDNA antibodies and serum IFN-a in SLE patients of both African-American and European ancestry. This is interesting, given the therapeutic effect of IFN-a in MS patients, and the pathogenic effect of this same cytokine in SLE. Further exploration of the impact of the IRF8 locus upon in vivo IFN-a levels could provide insight into both diseases.

To cite this abstract, please use the following information:
Franek, Beverly S., Kariuki, Silvia N., Arrington, Jasmine, Mikolaitis, Rachel A., Jolly, Meenakshi, Utset, Tammy O., et al; IRF8 Allele Associated with Susceptibility to Multiple Sclerosis Is Associated with Serum Interferon Alpha and Serologic Profile in Systemic Lupus Erythematosus. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :496
DOI: 10.1002/art.28265

Abstract Supplement

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