Background Systemic lupus erythematosus (SLE) is a chronic, multiorgan, autoimmune disease that affects people of all ages and ethnicities.
Objectives To explore the relationship between age at disease onset and many of the diverse manifestations of SLE. Additionally, to determine the relationship between age of disease onset and genetic risk in patients with SLE.
Methods The relationship between the age at disease onset and SLE manifestations were explored in a multi-racial cohort of 1317 patients. Patients with SLE 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, haemolytic anaemia, arthritis and leucopenia (OR=3.03, 2.13, 2.08, 2.50, 1.89, 1.53, respectively; p values <0.0001, 0.0004, 0.0005, 0.0024, 0.0114, 0.045, respectively). In female subjects, the odds of having cellular casts were 2.18 times higher in childhood-onset than in 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. However, late adult-onset patients with SLE have higher odds of developing photosensitivity than early adult-onset patients. Each SLE-susceptibility risk allele carried within the genome of patients with SLE increased the odds of having a childhood-onset disease in a race-specific manner: 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 The genetic contribution towards predicting early-onset disease in patients with SLE is quantified for the first time. A more severe SLE phenotype is found in patients with early-onset disease in a large multi-racial cohort, independent of gender, race and disease duration.
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Funding This work was supported by the NIH grant number R03AI076729 from the National Institute of Allergy and Infectious Diseases, and NIH grants numbers P20-RR015577, P20- RR020143, P30-AR053483, P01-AI083194, P01-AR049084, N01-AR62277, R37-AI024717, R01-AR042460, UL1-RR029882, P60-AR049459, UL1-RR024986, the Lupus Foundation of America, Merit Award from the US Department of Veterans Affairs, the University of Oklahoma Health Sciences Center, the Oklahoma City VA Medical Center and the Oklahoma Medical Research Foundation.
Competing interests None.
Ethics approval This study was conducted with the approval of the Oklahoma Medical Research Foundation and the University of Oklahoma Health Sciences Center.
Provenance and peer review Not commissioned; externally peer reviewed.
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