Background Pericarditis is a frequent complication of systemic lupus erythematosus (SLE) with potential for important compromise of cardiac function. Pericarditis is characterized by chest pain, pericardial friction rub, and detectable changes on electrocardiography or transthoracic echocardiogram. Its prevalence in SLE patients ranges from 12% to 56%, and its underlying mechanisms remain poorly understood. Treatment with glucocorticoids is commonly used to resolve pericardial effusions.

Methods 263 SLE patients with a minimum of 5-years of follow-up were studied, identifying individuals with a history of pericarditis based on clinical presentation and/or documented moderate to severe effusion. Gene expression analysis was conducted on prospectively collected longitudinal blood samples from 15 SLE patients with pericarditis history and 51 SLE patients without such history as controls, totaling 329 blood samples (an average of 5 samples per patient in each group). Differentially expressed genes were identified using limma and lme4 models to account for random effects.

Results There were no prominent demographic differences between the patient groups. However, patients of African ancestry were more represented in the pericarditis group (40% vs. 32%). The pericarditis group showed a higher rate of class IV lupus nephritis (27% vs. 16%) and increased incidence of myocardial infarction (4% vs. 1%), cardiomyopathy (6% vs. 1%), and deforming or erosive arthritis (14% vs. 9%), but a lower incidence of diabetes (1% vs. 6%). Gene expression analysis identified 82 differentially expressed genes between the groups (FDR 5%), with the COX7A1 mitochondrial gene being the most significantly downregulated gene in pericarditis patients. Notably, purine metabolism-related genes (FHIT, PAPSS1, PDE9A, GUCY1A2, NT5C3B) were affected among pericarditis patients according to KEGG pathway enrichment analysis. Laboratory data also indicated higher uric acid levels among pericarditis patients (OR 1.68 (0.54–2.81), p=0.006).

Discussion Pericarditis has known associations with uremia in gout disease and kidney failure, but a role for uric acid as a primary factor in predisposing SLE patients to pericarditis remains unreported. Interestingly, colchicine, recommended for acute and recurrent pericarditis in the general population, has shown success in treating SLE patients with pericarditis. Moreover, the downregulation of COX7A1 in peripheral blood might reflect the inflamed pericardium and its impaired serosal tissue function among SLE patients with pericarditis.