In the retrospective cohort study, Dr. Blazer and colleagues evaluated the prevalence of CVD across APOL1 genotypes in 100 SLE patients to test the hypothesis that the APOL1 phenotype for CVD is more penetrant in patients with SLE.
After completing polymerase chain reaction (PCR) sequencing, patients were stratified by genotype (ancestral, G0/G0; heterozygotes, RV/G0; and RV homozygotes, RV/RV) and clinical CVD endpoints were assessed by chart review.
The study found that APOL1 polymorphisms were associated with prevalent atherosclerotic disease in this cohort of SLE patients, with the risk of CVD increasing in patients who carried one or more APOL1 risk variants. The risk of CVD was 21.2% in patients with a G0/G0 genotype, 41.7% in those with RV/G0 genotype, and 63.6% in those with the RV/RV genotype.
After adjusting for other CVD risk factors (e.g., smoking, obesity, hypertension and early-stage renal disease), patients who carried one or more RV had a 3.1-fold increased risk of CVD (P=0.03) with the strongest association with total atherosclerotic disease (odds ratio [OR] of 6.9) and symptomatic disease (OR of 4.8).
When taken together, these results show the APOL1 risk variant is associated with prevalent CVD in this cohort of African Americans with SLE, said Dr. Blazer. “This suggests that SLE may be an important second hit in the relationship between APOL1 RV and CVD,” she said.
Simple Test for SLE Disease Activity Status
Chaim Putterman, MD, a clinical rheumatologist at the Albert Einstein College of Medicine, The Bronx, N.Y., described a simple test for assessing and monitoring SLE disease activity. The need for such a test, he said, is highlighted by the less-than-optimal tests currently used to assess disease activity. These tests make it challenging to predict and promptly identify and treat disease flares to reduce SLE-related morbidity and mortality. “Therefore, sensitive and specific diagnosis of disease activity remains an important unmet clinical need,” he said.
The simple test Dr. Putterman described employs immunosignature technology (IST) developed by the San Ramon, Calif., biotechnology company HealthTell Inc. The test uses assays to measure serum antibodies bound to a microarray of about 126,000 unique peptides to provide a broad sample. Statistical analysis of this sample is done to identify peptide features with binding intensities that are significantly different in persons with active vs. inactive SLE.
To evaluate the utility of the test, Dr. Putterman—who is a research collaborator and consultant at HealthTell—and his colleagues undertook a study to test the hypotheses on two points: that 1) the antibody profile of a patient with SLE identified with IST would reflect disease activity better than individual biomarkers, and 2) it may be possible to use changes in antibody profiles to monitor changes in disease activity.3