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.


Early Disease Onset Is Predicted by a Higher Genetic Risk for Lupus and Is Associated with a More Severe Phenotype in Lupus Patients.

Webb3,  Ryan, Kelly3,  Jennifer A., Somers7,  Emily C., Hughes3,  Travis, Kaufman4,  Kenneth M., Sanchez3,  Elena, Nath3,  Swapan K.

Cincinnati Children's Hospital Medical Center, VAMC, Oklahoma City, OK
Med Univ of South Carolina, Charleston, SC
Oklahoma Medical Research Foundation
Oklahoma Medical Research Foundation, University of Oklahoma, US Department of Veterans Affairs Medical Center
Oklahoma Medical Research Foundation, Uppsala University, Uppsala, Sweden
University of Michigan, Ann Arbor, MI
University of Michigan
University of Oklahoma, US Department of Veterans Affairs Medical Center, Oklahoma Medical Research Foundation, Oklahoma City, OK

Purpose:

Systemic lupus erythematosus (SLE) is a chronic, multi-organ, autoimmune disease that affects people of all ages and ethnicities. Herein, we explore the relationship between the age at disease onset and many of its diverse manifestations. We further determine the relationship between age of disease onset and genetic risk in SLE patients.

Methods:

We explore the relationship between the age at disease onset and SLE manifestations in a multi-ethnic cohort of 1,317 patients. SLE patients were genotyped across 19 confirmed genetic susceptibility loci for SLE. Logistic regression was used to determine the relationships between the number of risk alleles present and age of disease onset.

Results:

Childhood-onset SLE had higher odds of proteinuria, malar rash, anti-dsDNA antibody, hemolytic anemia, arthritis, and leukopenia (odds ratios = 3.03, 2.13, 2.08, 2.50, 1.89, 1.53, respectively, and p-values <0.0001, 0.0004, 0.0005, 0.0024, 0.011, and 0.045, respectively). In females, the odds of having cellular casts were 2.18 times higher in childhood-onset versus adult-onset SLE (p=0.0027). With age of onset >= 50, the odds of having proteinuria, cellular casts, anti-nRNP antibody, anti-Sm antibody, anti-dsDNA antibody, and seizures were reduced. Instead, late adult-onset SLE patients have higher odds of developing photosensitivity compared with early adult-onset patients (onset >=18 and <50 yrs). Importantly, each SLE-susceptibility risk allele carried within the genome of SLE patients increased the odds of having a childhood-onset disease in an ethnicity-specific manner: each risk allele increased risk by an average of 48% in Gullah, and 25% in African-Americans, but this was not significant in Hispanic and European-American lupus patients.

Conclusions:

We report and quantify for the first time the genetic contribution towards predicting early-onset disease in SLE patients. Furthermore, we report a more severe SLE phenotype in patients with an early-onset disease in a large multiethnic cohort, independent of gender, race, and disease duration.

To cite this abstract, please use the following information:
Webb, Ryan, Kelly, Jennifer A., Somers, Emily C., Hughes, Travis, Kaufman, Kenneth M., Sanchez, Elena, et al; Early Disease Onset Is Predicted by a Higher Genetic Risk for Lupus and Is Associated with a More Severe Phenotype in Lupus Patients. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1590
DOI: 10.1002/art.29356

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