EBV is a candidate trigger of rheumatoid arthritis (RA). We determined both EBV-specific T cell and B cell responses and cell-associated EBV DNA copies in patients with RA and demographically matched healthy virus carriers. Patients with RA showed increased and broadened IgG responses to lytic and latent EBV-encoded Ags and 7-fold higher levels of EBV copy numbers in circulating blood cells. Additionally, patients with RA exhibited substantial expansions of CD8+ T cells specific for pooled EBV Ags expressed during both B cell transformation and productive viral replication and the frequency of CD8+ T cells specific for these Ags correlated with cellular EBV copy numbers. In contrast, CD4+ T cell responses to EBV and T cell responses to human CMV Ags were unchanged, altogether arguing against a defective control of latent EBV infection in RA. Our data show that the regulation of EBV infection is perturbed in RA and suggest that increased EBV-specific effector T cell and Ab responses are driven by an elevated EBV load in RA.

Cytokines are supposed to play an essential role in the regulation of the bone metabolic unit. However, information on cytokine production of primary human osteoblasts from patients with metabolic bone disease is scarce, and few attempts have been made to correlate such data to histomorphometric parameters of individual patients. We investigated 11 patients with metabolic bone disease referred to our outpatient department for bone biopsy and analyzed interleukin (IL)-1, IL-6, and TNF-␣ protein release and gene expression in primary osteoblast cultures. Compared with four controls, five patients showed normal cytokine protein release, whereas six patients showed much higher levels of interleukin-6 (26-fold) and TNF-␣ (84-fold). All three cytokines were strongly correlated concerning gene expression and/or protein levels (r ‫؍‬ 0.72-0.96). Histomorphometric analysis of the bone samples showed that eroded surface (ES/BS) as a parameter of bone resorption was significantly associated with TNF-␣. In addition, RANKL gene expression was positively associated with ES/BS and osteoclast surface (Oc.S/BS

n-3 long-chain PUFA (n-3 LC-PUFA) may improve cardiovascular and inflammatory diseases. The effects of n-3 LC-PUFA-supplemented dairy products on inflammation and immunological parameters, biomarkers of oxidative stress, serum lipids, and on disease activity were determined in patients with rheumatoid arthritis (RA). Forty-five subjects (forty-three females and two males) were randomly divided into two groups in a double-blind, placebo-controlled cross-over study. Both groups received placebo or verum products consecutively for 3 months with a 2-month washout phase between the two periods. Blood samples were taken at the beginning and at the end of each period. The dairy products generally improved serum lipids by increasing HDL and lowering lipoprotein a. The n-3 LC-PUFA supplements act to lower TAG. Additionally, a decreased lipopolysaccharide-stimulated cylo-oxygenase-2 expression was found in patients who had consumed the enriched dairy products. The majority of the CD analysed were not influenced, although n-3 LC-PUFA did suppress the immune response as lymphocytes and monocytes were found to be significantly decreased. The n-3 LC-PUFA did not increase the biomarkers of oxidative stress such as 8-iso-PGF2α and 15-keto-dihydro PGF2α, and DNA damage like 7,8-dihydro-8-oxo-2′-deoxyguanosine. The long-term consumption of dairy products (2 × 12 weeks) diminished the excretion of hydroxypyridinium crosslinks, and favoured the diastolic blood pressure. The consumption of moderate doses of n-3 LC-PUFA in combination with dairy products did not improve the disease activity. However, there is evidence of cardioprotective effects. Furthermore, the long-term consumption of dairy products acts against the cartilage and bone destruction in RA.

The aim of our study was to compare the significance of risk factors for osteoporosis according to gender and menopausal state in patients with rheumatoid arthritis (RA). Bone mineral density (dual X-ray absorptiometry), cumulative glucocorticoid dose, age, disease duration, body mass index (BMI) and parameters of disease activity and bone turnover were registered in 343 postmenopausal women, 100 premenopausal women and 108 men with RA. Osteoporosis was found in a significantly higher percentage in postmenopausal women (55.7%) and in men (50.5%) in comparison with premenopausal women (18%; P < 0.001). The following risk factors for osteoporosis were found: older age, low BMI and high cumulative glucocorticoid dose in postmenopausal women, low BMI and high cumulative glucocorticoid dose in men and low BMI in premenopausal women. There is a very high prevalence of osteoporosis not only in postmenopausal women but also in men with RA. Osteoporosis risk factors are strongly dependent from gender and menopausal state.

The development of secondary osteoporosis in rheumatoid arthritis (RA) has recently become well recognized, characterized by demineralization at axial and in particular periarticular peripheral bone sites. Our aim was to evaluate multisite quantitative ultrasound (QUS) compared to digital X-ray radiogrammetry (DXR) by the quantification of cortical bone loss dependent on the severity of RA. Fifty-three patients with verified RA underwent QUS measurements (Sunlight Omnisense 7000) with estimation of the speed of sound (QUS-SOS) at the distal radius and at the phalanx of the third digit. Also, bone mineral density (DXR-BMD) and metacarpal index (DXR-MCI) were estimated on metacarpals II-IV using DXR technology. Additionally, Larsen score and Steinbroker stage were assessed. Disease activity of RA was estimated by disease activity score 28 (DAS 28). For the group with minor disease activity (3.2 5.1), QUS-SOS of the radius revealed a significant correlation to DXR-BMD (R = 0.71) and DXR-MCI (R = 0.84), whereas for QUS-SOS (phalanx) no significant association to the DXR parameters was shown. The DXR parameters and, to a lesser extent, the QUS data also demonstrated pronounced declines in the case of accentuated disease activity (DAS > 5.1). Both DXR-BMD (-25.9 %, P < 0.01) and DXR-MCI (-38.6 %, P < 0.01) revealed a notable reduction dependent on the severity of RA. Otherwise, QUS-SOS marginally decreased, with -2.6% (radius) and -3.9% (phalanx). DXR revealed a significant reduction of DXR-BMD as well as DXR-MCI dependent on the severity of RA and surpassed multisite QUS as a promising diagnostic tool.