ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1638

High Genetic Risk Score Is Associated with Increased Organ Damage in SLE

Sarah Reid1, Andrei Alexsson1, Martina Frodlund2, Johanna K Sandling1, Elisabet Svenungsson3, Andreas Jönsen4, Christine Bengtsson5, Iva Gunnarsson3, Anders A. Bengtsson4, Solbritt Rantapaa-Dahlqvist5, Maija-Leena Eloranta1, Ann-Christine Syvänen6, Christopher Sjöwall2, Lars Rönnblom1 and Dag Leonard1, 1Rheumatology and Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Sweden, Uppsala, Sweden, 2Department of Clinical and Experimental Medicine, Linköping University, Sweden, Linköping, Sweden, 3Rheumatology Unit, Department of Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden, 4Lund University, Department of Clinical Sciences, Rheumatology, Lund, Sweden, 5Dept of Public Health and Clinical Medicine/Rheumatology, Umeå University, Sweden, Umeå, Sweden, 6Uppsala University, Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala, Sweden

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: ,

Session Information

Date: Monday, November 6, 2017

Title: Systemic Lupus Erythematosus – Clinical Aspects and Treatment Poster II: Damage and Comorbidities

Session Type: ACR Poster Session B

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

Background/Purpose:

Systemic lupus erythematosus (SLE) is a chronic, autoimmune disease with a complex genetic etiology. Over 80 risk genes for SLE have been identified and some genetic variants have demonstrated association with specific disease manifestations, such as STAT4 and nephritis. The overall effect of a patient’s hereditary risk factors on disease severity has so far not been studied. We therefore assessed the relationship between high genetic risk and development of organ damage in SLE.

Methods:

Patients with SLE, who met at least 4 ACR criteria (n = 1012), were genotyped

using a 200K Immunochip SNP Array (Illumina). A genetic risk score (GRS) was assigned to

each patient based on the single nucleotide polymorphisms (SNPs) which in previous studies have shown association (p<5×10-8) with SLE according to Morris, et al (Nat Genet, 2016. 48(8): p. 940-6). For 32 loci the SLE GWAS SNP was available on the ImmunoChip. For each SNP, the natural logarithm of the odds ratio (OR) for SLE susceptibility was multiplied by the number of risk alleles in each individual. The sum of all products for each patient was defined as the GRS. Information regarding organ damage according to Systemic Lupus International Collaborating Clinics / American College of Rheumatology Damage Index (SLICC-DI), disease manifestations, antibody profile, medication, current disease activity, age at diagnosis and sex was retrieved from medical records. Statistical analyzes were performed using Statistica 13.2 (Statsoft).

Results:

In an ordinal regression model, with SLICC-DI (0, 1, 2, 3, 4 and >4 points) as outcome and age and GRS as independent variables, an association was found between GRS and SLICC-DI (OR1.16 (1.03-1.31), p=0.015). The relationship was more pronounced for patients under 60 years of age (OR1.30 (1.11-1.52) p=7.1×10-4). Using a linear regression model, a negative relationship was observed between GRS and age at diagnosis (β = -0.13, p=1.5×10-5).When analyzing the 11 SLE criteria (ACR-82) using a logistic regression model associations were observed between GRS and nephritis (OR 1.26 (1.09-1.45), p=0.0015), the immunological criteria (OR 1.31 (1.13-1.51), p = 3.2×10-4) and arthritis (OR 0.84 (0.71-1.00), p=0.044). A high GRS was also associated with presence of anti-dsDNA (OR 1.37 (1.15-1.62), p=9.4×10-7) and low complement levels (OR 1.32 (1.03-1.68), p=0.044). No association was observed between GRS and disease activity at the time of follow-up and there was no difference in GRS between men and women with SLE.

Conclusion:

In patients with SLE, there is an association between a high genetic risk score and early disease onset. In addition, patients with high genetic risk scores have a higher risk of developing permanent organ damage compared to individuals with fewer risk genes. Our findings indicate that genetic profiling of patients with SLE may provide a tool for predicting severity of the disease.

Disclosure: S. Reid, None; A. Alexsson, None; M. Frodlund, None; J. K. Sandling, None; E. Svenungsson, None; A. Jönsen, None; C. Bengtsson, None; I. Gunnarsson, None; A. A. Bengtsson, None; S. Rantapaa-Dahlqvist, None; M. L. Eloranta, None; A. C. Syvänen, None; C. Sjöwall, None; L. Rönnblom, None; D. Leonard, None.

To cite this abstract in AMA style:

Reid S, Alexsson A, Frodlund M, Sandling JK, Svenungsson E, Jönsen A, Bengtsson C, Gunnarsson I, Bengtsson AA, Rantapaa-Dahlqvist S, Eloranta ML, Syvänen AC, Sjöwall C, Rönnblom L, Leonard D. High Genetic Risk Score Is Associated with Increased Organ Damage in SLE [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/high-genetic-risk-score-is-associated-with-increased-organ-damage-in-sle/. Accessed .

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