Toll-like receptor 3 and interleukin 1ß expression in CD34+ cells from patients with rheumatoid arthritis: association with inflammation and vascular involvement.

OBJECTIVES: Circulating proangiogenic haematopoietic cells (PHCs), including CD34+ cells, play an important role in endothelial homeostasis. Among PHCs, CD34+ cells are the largest cell population, thus, much of the regenerative/reparative potential of PHCs may be attributed to CD34+ cells. Our aim was to determine the association between inflammation and CD34+ cell number, intracellular levels of reactive oxygen species (ROS) and expression of Toll-like receptor 3 (TLR3) and interleukin 1ß (IL-1ß), arterial stiffness (AS) indices, and carotid intima-media thickness (cIMT) in patients affected by rheumatoid arthritis (RA). METHODS: CD34+ cells were isolated from 24 RA patients and 26 matched controls. ROS levels, TLR3 and IL-1ß expression were measured. C-reactive protein (CRP), fibrinogen, AS, and cIMT were also evaluated. RESULTS: CD34+ count was lower in RA patients as compared to controls. In CD34+ cells from RA patients, ROS, TLR3 and IL-1ß expressions were increased compared to controls. In RA patients, we found higher CRP and fibrinogen levels, and higher values of Pulse Wave Velocity (PWV) and Augmentation Index (AIx), both AS indices, and of cIMT. CD34+ cell numbers were inversely correlated with CRP, TLR3, IL-1ß, ROS, and AS indices. TLR3 levels were related to CRP, IL-1ß, fibrinogen and ROS. IL-1ß levels were correlated with expression of CRP, ROS, and PWV. CONCLUSIONS: Inflammatory status in RA is associated with an increased expression of TLR3 and of IL-1ß in CD34+ cells, which appear to affect cell number. These new findings suggest a perspective on accelerated atherosclerosis and vascular damage in RA.

Vitamin D Status in Rheumatoid Arthritis: Inflammation, Arterial Stiffness and Circulating Progenitor Cell Number.

BACKGROUND AND AIMS: Suboptimal vitamin D status was recently acknowledged as an independent predictor of cardiovascular diseases and all-cause mortality in several clinical settings, and its serum levels are commonly reduced in Rheumatoid Arthritis (RA). Patients affected by RA present accelerated atherosclerosis and increased cardiovascular morbidity and mortality with respect to the general population. In RA, it has been reported an impairment of the number and the activity of circulating proangiogenic haematopoietic cells (PHCs), including CD34+, that may play a role in endothelial homeostasis. The purpose of the study is to investigate the association between vitamin D levels and PHCs, inflammatory markers, and arterial stiffening in patients with RA. METHODS AND RESULTS: CD34+ cells were isolated from 27 RA patients and 41 controls. Vitamin D levels, C-reactive protein (CRP), fibrinogen, pulse wave velocity (PWV), and carotid intima-media thickness (cIMT) were also evaluated. CD34+ count and vitamin D levels were lower in RA patients as compared to controls, while fibrinogen, CRP, PWV and cIMT were higher in RA patients. CD34+ cell number appeared to be associated with vitamin D levels, and negatively correlated to fibrinogen and early atherosclerosis markers (PWV and cIMT); vitamin D levels appear also to be inversely associated to fibrinogen. CONCLUSIONS: RA patients with moderate disease activity presented with low vitamin D levels, low CD34+ cell count, increased PWV and cIMT; we found that vitamin D deficiency is associated to CD34+ cell reduction in peripheral blood, and with fibrinogen levels. This suggests that vitamin D might contribute to endothelial homeostasis in patients with RA.

Central nervous system vasculitis after starting methimazole in a woman with Graves' disease.

BACKGROUND: Graves' disease (GD), a prototypical autoimmune disorder, is associated with other autoimmune diseases, including vasculitis. Antithyroid drugs, despite their postulated immunosuppressive effects, may cause several autoimmune disorders. Here we describe the first patient with central nervous system (CNS) vasculitis that developed shortly after the start of methimazole (MMI) treatment for GD. PATIENT FINDINGS: CNS vasculitis was suspected on the basis of the clinical features and neurologic examination, showing a reinforcement of deep reflexes, especially of the left knee and Achilles reflexes. The diagnosis was confirmed by a brain magnetic resonance imaging (MRI), which showed some hyperintensive spots in the subcortical substantia alba and in the parietal area bilaterally, and by a single-photon emission computed tomography (SPECT) imaging, which showed a nonhomogenous distribution of the blood flow in the brain, with a reduced perfusion on the left side of the frontotemporal and parietal regions, and on the right side of the frontotemporal area. MMI was stopped before total thyroidectomy, and symptoms resolved in the next 5 weeks. Six months after MMI was stopped, the brain MRI and SPECT had become normal. SUMMARY: To our knowledge, this is the first report of CNS vasculitis related to MMI therapy.