ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1019

Type I Interferon Levels Vary with Regional Ancestry in European-derived SLE Cohorts

Justine Shum1, Yogita Ghodke-Puranik 2, Regine Tipon 2, Jessica Dorschner 3, Danielle Vsetecka 3, Shreyasee Amin 4, Ashima Makol 5, Floranne Ernste 4, Thomas Osborn 5, Kevin Moder 3, Vaidehi Chowdhary 3, Uma Thanarajasingam 6, Vilija Oke 7, Iva Gunnarsson 7, Agneta Zickert 7, Maria Zervou 8, Elisabet Svenungsson 9, George Goulielmos 8 and Timothy Niewold 2, 1NYU School of Medicine, New York, 2Colton Center for Autoimmunity, NYU School of Medicine, New York, 3Mayo Clinic, Rochester, 4Mayo Clinic Rochester, Rochester, MN, 5Mayo Clinic Minnesota, rochester, MN, 6Mayo Clinic, Rochester, MN, 7Karolinska Institutet, Stockholm, Sweden, 8University of Crete, Crete, Greece, 9Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden

Meeting: 2019 ACR/ARP Annual Meeting

Keywords: ,

Session Information

Date: Monday, November 11, 2019

Title: SLE – Etiology & Pathogenesis Poster I

Session Type: Poster Session (Monday)

Session Time: 9:00AM-11:00AM

Background/Purpose: Type I interferon (IFN) is an important mediator in the pathogenesis of systemic lupus erythematosus.  Serum type I IFN levels clearly vary between SLE patients of different continental ancestral backgrounds, with levels being highest in African-American SLE patients.  It is not known whether this diversity is also present within continental ancestral groups.  In this study, we examine regional differences between European populations and use ancestry informative markers (AIMs) to assess for Northern versus Southern European admixture in a European-American cohort, and to correlate proportional regional European ancestry with serum type I IFN activity.

Methods: We studied type I IFN levels in European ancestry SLE patient cohorts from Sweden, Crete and the United States.  Patients all met the ACR classification criteria for SLE. Serum IFN-a activity was determined using a WISH cell reporter assay.  In the United States cohort, a validated set of European American ancestry informative markers (AIMs) designed to distinguish northwest and southeast European ancestry was used to assess for proportional Northern versus Southern European ancestry. Principal component analysis (PCA) was performed to infer population structure.

Results: The Swedish cohort had the highest type I IFN levels, while the US cohort was intermediate, and the lowest IFN levels were detected in the Crete cohort.  The US subjects are a mix of Northern and Southern European ancestry by self-report, so we genotyped 297 ancestry informative markers in the 366 US SLE patients with self-reported European American ancestry.  In this group, circulating type I IFN levels were correlated with three of the top five principal components derived from the AIMs considered in aggregate using Fisher’s method for the combination of p-values across the three components (p = 0.024). Given that these components segregate northern versus southern European ancestry, this finding in the US cohort supports the concept that type I IFN levels vary according to regional genetic ancestry within Europe.

Conclusion: In this study, we demonstrate that variations in type I IFN levels correlate with regional ancestry within Europe in European-derived cohorts of SLE patients, further supporting the heterogeneity in type I IFN pathway activation in SLE patients of different ancestral backgrounds.  

Disclosure: J. Shum, None; Y. Ghodke-Puranik, None; R. Tipon, None; J. Dorschner, None; D. Vsetecka, None; S. Amin, None; A. Makol, None; F. Ernste, None; T. Osborn, None; K. Moder, None; V. Chowdhary, None; U. Thanarajasingam, None; V. Oke, None; I. Gunnarsson, None; A. Zickert, None; M. Zervou, None; E. Svenungsson, None; G. Goulielmos, None; T. Niewold, None.

To cite this abstract in AMA style:

Shum J, Ghodke-Puranik Y, Tipon R, Dorschner J, Vsetecka D, Amin S, Makol A, Ernste F, Osborn T, Moder K, Chowdhary V, Thanarajasingam U, Oke V, Gunnarsson I, Zickert A, Zervou M, Svenungsson E, Goulielmos G, Niewold T. Type I Interferon Levels Vary with Regional Ancestry in European-derived SLE Cohorts [abstract]. Arthritis Rheumatol. 2019; 71 (suppl 10). https://acrabstracts.org/abstract/type-i-interferon-levels-vary-with-regional-ancestry-in-european-derived-sle-cohorts/. Accessed .

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