Lymphopenia is a risk factor in the progression of carotid intima‐media thickness in juvenile‐onset systemic lupus erythematosus

Abstract

Objective. To characterize the atherosclerotic risk factors in the progression of subclinical atherosclerosis in patients with juvenile-onset systemic lupus erythematosus (SLE).Methods. This was a longitudinal study of 76 patients with juvenile-onset SLE. Carotid arteries were evaluated using ultrasonography at baseline and at followup visits at 6-month intervals over the 6-year study period. Clinical and laboratory parameters, disease activity, treatment, and traditional risk factors for atherosclerosis were evaluated. Data were analyzed using generalized estimating equations.Results. The mean ؎ SD age of the patients at baseline was 15.01 ؎ 3.48 years and the mean ؎ SD disease duration was 2.65 ؎ 2.5 years. The mean ؎ SD duration of followup was 3.74 ؎ 1.24 years. The mean ؎ SD intima-media thickness (IMT) of the common carotid arteries differed significantly between the patient and control (n ‫؍‬ 38) groups (0.63 ؎ 0.08 mm versus 0.54 ؎ 0.06 mm; P < 0.001). The presence of lymphopenia at diagnosis and at baseline and higher levels of serum creatinine and C-reactive protein at baseline were positively associated with progression of carotid IMT (P ‫؍‬ 0.006, P ‫؍‬ 0.043, P ‫؍‬ 0.037, and P ‫؍‬ 0.049, respectively). In multivariate analysis, only lymphopenia at baseline and at diagnosis were consistently associated with progression of IMT (P ‫؍‬ 0.012 and P ‫؍‬ 0.045, respectively).Conclusion. In patients with juvenile-onset SLE, some nontraditional risk factors for the progression of subclinical atherosclerosis were identified. Lymphopenia was the only independent risk factor for the progression of IMT. The pathogenic mechanisms warrant further investigation.

Pediatric lupus in Asia

“…Most of them were benign, limited and without postherpetic neuralgia. 38 leukopenia on SLE diagnosis, lymphopenia on SLE diagnosis, higher creational level, CRP >5 mg/l were positively associated with progression of intima-media thickening by univariate analysis. (p ¼ 0.027, 0.006, 0.037 and 0.048, respectively).…”

Reply

“…This hypothesis is raised because of previous reports indicating that leukopenia is associated with atherosclerosis in SS (1) and that lymphopenia is associated with atherosclerosis in SLE (2). Their study also reveals that anti-SSA antibodies are a risk factor for the progression of atherosclerosis, and data from SLE studies showed that lymphopenia is highly associated with the presence of anti-SSA antibodies (3).…”

“…There were no differences in the baseline carotid IMT between patients with and those without (mean Ϯ SD 0.62 Ϯ 0.07 versus 0.64 Ϯ 0.09; P ϭ 0.26). Furthermore, we used the generalized estimating equation (GEE) method to analyze the correlation between the anti-SSA antibody data and the progression of atherosclerosis (2). Progression of IMT was not associated with the presence of anti-SSA antibodies (P ϭ 0.93) in univariate analysis.…”

“…We did not state in our article that the issue of the thromboprotective effects of antimalarials had only been addressed in studies involving populations without SLE but were instead referring to the findings of 2 prospective studies in non-SLE populations (1,2). We referred to other descriptive and observational studies in SLE, and acknowledge that we did not refer to all available publications on this topic and that 2824 LETTERS…”

Subclinical Atherosclerosis in Systemic Autoimmune Disorders

“…The role of SLE activity in the formation of non calcified coronary plaque (NCP) was investigated by Kiani et al; unlike coronary calcium, which is not associated with SLE activity measures or with active serologies, NCP is more common in patients with active disease (Kiani, Vogel-Claussen et al 2010). Additionally, the presence of lymphopenia and higher levels of serum creatinine and CRP seem to be disease related risk factors in the progression of carotid IMT in juvenile-onset SLE as demonstrated by Huang et al (Huang, Chung et al 2009). In particular, lupus EPCs/CACs (myeloid circulating angiogenic cells) have decreased capacity to differentiate into mature ECs and synthesize decreased amounts of the molecules vascular endothelial growth factor and hepatic growth factor (Rajagopalan, Somers et al 2004;Denny, Thacker et al 2007;Lee, Li et al 2007;Moonen, de Leeuw et al 2007;Westerweel, Luijten et al 2007).…”