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ID PMID Title PublicationDate abstract
23328621 Serum acute phase protein and inflammatory cytokine network correlations: comparison of a 2013 Serum concentrations of acute phase proteins, inflammatory cytokines, and other immunological components were individually assayed using high-sensitivity ELISA in a com-munity-based cohort of preclinical rheumatoid arthritis (pre-RA) and matched non-RA control (CN) subjects. Bivariate correlations of the biomarker panel concentrations were compared in pre-RA versus CN and female versus male subjects. Clinically elevated CRP levels (8+ mg/l) occurred in a higher (p = 0.010) frequency in 46 pre-RA (n = 8, 17.4%) subjects than in 179 CN (n = 9, 5.0%), and were independent of age, gender, smoking behaviors, and serum rheumatoid factor. Selected age and gender differences were found in levels of the immunological network factors. In each study group, the ratio of sTNF-RI to IL-2sRα mean concentrations was 2-fold higher in men than in women. Aging correlated positively with CRP, ASAA, and TNF-α levels, but negatively with IL-1β. Bivariate correlations were similar in pre-RA subjects versus CN and by gender, with few exceptions. Factor loadings in principal component analysis of the total subjects indicated that age- and gender-related variables constituted the two main components. Using multiple regression analyses, an integrative working model of all variable interrelations was generated. The tentative, directional model supports a concept of gender dimorphism of the ratio of sTNF-RI to IL-2sRα serum concentrations and displays differing effects of age on TNF-α versus IL-1β levels. These findings indicate complex age, gender, and cytokine interrelations in control of the immune systems network. Future research in testing such inflammatory pathways promises a better understanding of predisposition to diseases, like RA.
23588940 Association of polymorphisms modulating low-density lipoprotein cholesterol with susceptib 2013 Jun OBJECTIVE: Dyslipidemia, a risk factor for cardiovascular diseases, is more prevalent in patients with rheumatoid arthritis (RA) than in the general population. We investigated whether single-nucleotide polymorphisms (SNP) modulating low-density lipoprotein (LDL) cholesterol affect susceptibility, severity, and progression of RA. METHODS: We enrolled 302 patients with RA and 1636 healthy controls, and investigated the SNP modulating LDL cholesterol. Clinical characteristics of RA, serum adipocytokine concentrations, and radiographic severity were analyzed according to genotype score based on the number of unfavorable alleles. The influence of genotype score on radiographic progression was also investigated using multivariable logistic models. RESULTS: We identified 3 SNP (rs688, rs693, and rs4420638) modulating LDL cholesterol in Koreans, which correlated well with LDL cholesterol levels in both patients with RA and controls. Among them, 2 SNP, rs688 and rs4420638, were more prevalent in patients with RA than in controls. In patients with RA carrying more unfavorable alleles (genotype score ≥ 3), disease activity measures, serum adipocytokine levels, and radiographic severity were all increased. The genotype score was an independent risk factor for radiographic progression of RA over 2 years, and its effect was greater than the influence of conventional risk factors. CONCLUSION: SNP modulating LDL cholesterol influence the risk, activity, and severity of RA. These results provide the first evidence that genetic mechanisms linked to dyslipidemia may directly contribute to the susceptibility and prognosis of RA, a representative of chronic inflammatory diseases, explaining the high incidence of dyslipidemia in RA.
23411650 Relationship of the HLA-DRB1 alleles and seropositivity, anti-MCV, functional status and r 2013 OBJECTIVES: The HLA-DRB1 gene plays an important role in the genetic predisposition to rheumatoid arthritis. The anti-citrullinated protein antibody (ACPA) is known to be associated with the susceptibility to rheumatoid arthritis (RA), as well as the severity of the disease. The aim of this study is to determine the HLA genes that are associated with the severity of the RA measured by seropositivity, functional status, radiological damage and the anti-modified citrullinated vimentin (MCV) levels. MATERIAL AND METHOD: Ninety-six patients diagnosed with rheumatoid arthritis and a control group consisting of 84 healthy individuals were enrolled in the study. The HLA-DRB1 type and subtypes were specified using the polymerase chain reaction with sequence-specific primers (PCR-SSP). The association of the HLA-DRB1 type and subtypes with seropositivity, anti-MCV levels, functional status and anatomical joint damage were explored using the modified Larsen scoring method. RESULTS: The DRB1*01, DRB1*04, DRB1*07, DRB1*10, DRB1*11 and DRB1*15 alleles were found to be related with higher anti-MCV levels (p< 0.05). The DRB1*11 type and the DRB1*1001 subtype were observed to be associated with poor functional status (Stages 3-4). The DRB1*0801 subtype was associated with lower anti MCV levels (OR=8.35, p=0.02). DRB1*04 type and DRB1*0405 subtypes were related with radiological damage (OR=0.52 and 0.25; p=0.04 and 0.03, respectively). No significant relationship was observed between the RF seropositivity and the HLA-DRB1 alleles. CONCLUSION: This study revealed the association between the HLA alleles and seropositivity, functional status, anti-MCV levels and radiological damage in patients in the Southeast Anatolian region of Turkey.
24015711 Antibodies to N-homocysteinylated albumin and haemoglobin in patients with rheumatoid arth 2014 OBJECTIVES: To investigate whether anti-Nε-homocysteinylated albumin (anti-N-Hcy-Alb) and haemoglobin (anti-N-Hcy-Hb) antibodies occur in rheumatoid arthritis (RA) and whether they are associated with RA activity and/or severity. METHOD: Plasma total homocysteine (tHcy) and serum anti-N-Hcy-Alb and -Hb antibodies levels were determined in 76 RA patients (12 men and 64 women, median age 56 years) and 80 age- and sex-matched controls. RESULTS: RA patients compared to healthy controls demonstrated elevated tHcy [median (IQR), 13.20 (3.80) vs. 9.45 (3.25) μmol/L; p < 0.000001] and anti-N-Hcy-Alb and -Hb antibodies [absorbance at 490 nm, median (IQR), 0.546 (0.085) vs. 0.452 (0.056) and 0.649 (0.106) vs. 0.532 (0.057), respectively; all p < 0.000001]. In RA patients, RA radiological class was a strong independent predictor of tHcy [β (SE), 0.59 (0.11); p = 0.000001] and anti-N-Hcy-Alb [0.36 (0.12); p = 0.003] and -Hb [0.49 (0.11); p = 0.00007] antibodies. The number of swollen joints, but not C-reactive protein (CRP), interleukin 6 (IL-6), positive rheumatoid factor (RF), or anti-cyclic citrullinated peptide (anti-CCP) antibodies, showed independent effects on anti-N-Hcy-Alb [β (SE), 0.36 (0.11); p = 0.001] and -Hb [0.25 (0.11); p = 0.02] antibodies. Anti-N-Hcy-Hb antibodies, but not those against N-Hcy-Alb, were positively correlated with RA functional class and RA duration. No effect of any medications on tHcy or anti-N-Hcy-protein antibodies was observed. CONCLUSIONS: This study is the first to show that RA is characterized by enhanced autoimmune response to Nε-homocysteinylated proteins detectable in circulating blood, which is related to some clinical measures of RA severity.
24988887 Calreticulin promotes angiogenesis via activating nitric oxide signalling pathway in rheum 2014 Nov Calreticulin (CRT) is a multi-functional endoplasmic reticulum protein implicated in the pathogenesis of rheumatoid arthritis (RA). The present study was undertaken to determine whether CRT was involved in angiogenesis via the activating nitric oxide (NO) signalling pathway. We explored the profile of CRT expression in RA (including serum, synovial fluid and synovial tissue). In order to investigate the role of CRT on angiogenesis, human umbilical vein endothelial cells (HUVECs) were isolated and cultured in this study for in-vitro experiments. Our results showed a significantly higher concentration of CRT in serum (5·4 ± 2·2 ng/ml) of RA patients compared to that of osteoarthritis (OA, 3·6 ± 0·9 ng/ml, P < 0·05) and healthy controls (HC, 3·7 ± 0·6 ng/ml, P < 0·05); and significantly higher CRT in synovial fluid (5·8 ± 1·2 ng/ml) of RA versus OA (3·7 ± 0·3 ng/ml, P < 0·05). High levels of CRT are expressed in synovial membrane localized predominantly to inflammatory cells and synovial perivascular areas in both the lining and sublining layers of RA synovial tissue (RAST). Increased nitric oxide (NO) production and phosphorylation level of endothelial nitric oxide synthase (eNOS) were measured in HUVECs following CRT stimulation, while the total eNOS expression was not significantly changed. Furthermore, CRT promoted the proliferation, migration and tube formation of HUVECs, which were significantly inhibited by a specific eNOS inhibitor. These findings suggested that CRT may be involved in angiogenesis events in RA through NO signalling pathways, which may provide a potential therapeutic target in the treatment of RA.
24313545 Circulating progenitor cells in rheumatoid arthritis: association with inflammation and ox 2014 OBJECTIVES: To evaluate the association between inflammation, oxidative stress, and circulating progenitor cell (CPC) number and redox equilibrium, vascular lesions and accelerated atherosclerosis in rheumatoid arthritis (RA). METHOD: Circulating CD34+ cells were isolated from 33 RA patients and 33 controls. Reactive oxygen species (ROS) levels and mRNA expression of manganese superoxide dismutase (MnSOD), catalase (CAT), glutathione peroxidase type 1 (GPx-1) antioxidant enzymes, and the gp91phox-containing nicotinamide adenine dinucleotide phosphate (NADPH) oxidase NOX2 were measured in CD34+ cells. C-reactive protein (CRP), fibrinogen, erythrocyte sedimentation rate (ESR), carotid intima-media thickness (cIMT), and arterial stiffness (AS) were also evaluated. We investigated the relationships between inflammatory markers, vascular parameters, cell number, and antioxidant enzymes. RESULTS: CD34+ cell number was lower in RA patients than in controls. In CD34+ cells from RA patients, ROS levels, MnSOD mRNA, and NOX2 mRNA were higher, while mRNA expression of GPx-1 and CAT was significantly lower. The AS, pulse wave velocity (PWV), and augmentation index (AIx) were higher, as was cIMT. CD34+ cell number was inversely correlated with CRP, ROS, PWV, and AIx, and with the CAT/MnSOD and GPx-1/MnSOD ratios. CRP was correlated with MnSOD mRNA, PWV, and AIx but not with CAT and GPx-1 mRNA. CONCLUSIONS: Our data show a link between inflammation, oxidative stress, and the impairment of the antioxidant system of CPCs and their number, and with arterial stiffness in RA subjects. This could suggest a perspective on the accelerated development of vascular damage and atherosclerosis in RA.
23938142 Multidetector computed tomography findings of the sternoclavicular joint in patients with 2013 Nov We evaluated the multidetector computed tomography (MDCT) findings of the sternoclavicular joint in patients with rheumatoid arthritis (RA) and compare them with general population. Chest MDCT scans of RA patients were reviewed. The control group was formed from age and sex-matched individuals. The most common CT findings were cortical irregularity, joint space narrowing, and osteophytes in study group. There were no statistically significant differences in the MDCT findings between the two groups except that osteophytes were observed more often in the control group. It is difficult to distinguish between the involvement of RA and age-related degenerative changes at the sternoclavicular joint.
23961672 [Abatacept]. 2013 Jul Rheumatoid arthritis (RA) is an autoimmune disease that targets synovial joints and leads to bone destruction and joint deformity. T cell activations were shown to be involved in the onset of RA. T cells may control downstream inflammatory mediators reaching the synovium, where inflammation leads to joint destruction. However the treatment of RA has improved considerably in recent years through the introduction of DMARDs such as MTX, and anti-tumor necrosis factor therapy, there is still unmet medical need. Not a few patients experience an inadequate response to these therapies. Abatacept, a fusion protein of the extracellular domain of CTLA4 (a molecule inhibits the costimulatory pathway in T cell activation) and the Fc domain of human IgG1, was developed for the treatment of RA. Abatacept has shown long-term efficacy and safety in RA patients who were inadequate to MTX and/or anti-tumor necrosis factor therapy.
23800433 IL-33 in rheumatoid arthritis: potential role in pathogenesis and therapy. 2013 Sep Rheumatoid arthritis (RA) is characterized by chronic inflammatory disease, including synovial proliferation and excessive pro-inflammatory cytokines production, leading to cartilage and bone destruction. Cytokine-mediated immunity plays an important role in the pathogenesis of various autoimmune diseases such as RA. Recently, the IL-1 family member IL-33, was recognized to perform as an inflammatory cytokine, exerted profound effects in human RA and experimental inflammatory arthritis. Furthermore, inhibition of IL-33 signaling proposed a potential therapeutic approach. In this review, we summarize recent advances on the pathological roles of IL-33 in RA and discuss the therapeutic significance of these new findings.
24133964 [Progress in the study of BLyS and APRIL on regulating T cell responses in rheumatoid arth 2013 Jul B lymphocyte stimulator (BLyS), a tumor neurosis factor ligand superfamily, is an important factor of B cell survival and activation. However, BLyS also regulates T cell activation and survival, playing key roles in T cell-mediated autoimmune disorders. In the paper, we introduced the mechanisms of BLyS and a proliferation-inducing ligand (APRIL) regulating T cell responses and their roles in rheumatoid arthritis (RA).
23881264 A comparison of impact of fatigue on cognitive, physical, and psychosocial status in patie 2013 Dec This study was performed to compare the impact of fatigue on different aspects of quality of life in patients with rheumatoid arthritis (RA) and fibromyalgia syndrome (FM). This study involved subjects with FM (n = 45) and RA (n = 44). Impact of fatigue on physical, cognitive, and psychosocial status was measured with Fatigue Impact Scale (FIS) and health-related quality of life (HRQoL) with the Medical Outcome Study Short Form 36 (SF-36). Multiple regression analyses were used to evaluate impact of fatigue on quality of life by taking into account clinical symptoms and disease activity scores in these two patient groups. Although the severity of fatigue assessed by FSS was the same in FM and RA; according to Fatigue Impact Scale, fatigue has higher impact on cognitive function in FM (mean ± SD; 28.8 ± 19.9), and on the other hand, it has higher impact on mainly physical component (mean ± SD; 26.3 ± 4.9) in RA. Regarding all the clinical symptoms and disease activity scores, multiple regression models showed that fatigue together with pain affected the HRQoL (SF-36) in both patient groups. Fatigue has different impacts on QoL in FM and RA, respectively. Together with pain, fatigue lead FM patients to see disease as having worse health in terms of mental function, whereas it leads to poor health in terms of physical function in RA.
24435352 Cumulative disease activity predicts incidental hearing impairment in patients with rheuma 2014 Mar We previously reported that 24% of 113 rheumatoid arthritis (RA) patients had hearing impairment (HI). We investigated if disease activity was a predictor of incidental HI. One hundred and four patients completed three consecutive 6 months-apart rheumatic evaluations and concomitant audiometric evaluations which included at least an interview, an otoscopic evaluation, and a pure tone audiometry. HI was defined if the average thresholds for at least one of low-, mid-, or high-frequency ranges were ≥25 decibels (dB) hearing level in one or both ears. Appropriated statistics was used. Internal review board approval was obtained. Patients were most frequently middle-aged (43.4 ± 13.3 years), female (89.4%), and had median disease duration of 5 years and low disease activity. All were receiving RA treatment. At inclusion, 24 patients had HI which was sensorineural in 91.7% of them. Among the 80 patients without HI at baseline, 10 (12.5%) developed incidental HI, and they had more disease activity either at baseline ([median, range] disease activity score-28 joints evaluated-C-reactive protein [DAS28-CRP], 3.9 [1.6-7.3] vs. 2.1 [1-8.7], p = 0.006) or cumulative previous incidental HI (3.4 [1.8-4.8] vs. 2 [1-6.2], p = 0.007) and were more frequently on combined methotrexate and sulfasalazine (20 vs. 1.4%, p = 0.05) than their counterparts. In the adjusted Cox proportional model, cumulative DAS28-CRP was the only variable to predict incidental HI (odds ratio, 1.8; 95% confidence interval, 1.1-2.7; p = 0.01). Almost 13% of RA patients with short disease duration and low disease activity developed incidental HI during 1 year. Cumulative disease activity predicted incidental HI.
25126574 Blood monocyte subsets and selected cardiovascular risk markers in rheumatoid arthritis of 2014 OBJECTIVES: To evaluate blood monocyte subsets and functional monocyte properties in patients with rheumatoid arthritis (RA) of short duration in the context of cardiovascular (CV) risk and disease activity. METHODS: We studied conventional markers of CV risk, intima media thickness (IMT), and blood monocyte subsets in 27 patients aged 41 ± 10 years with RA of short duration (median 12 months) and 22 healthy controls. The RA subjects were divided into low (DAS28: 2.6-5.1) and high (DAS28 > 5.1) disease activity. RESULTS: RA patients exhibited increased levels of intermediate (CD14(++)CD16(+)) monocytes with decreased CD45RA expression compared to controls, increased counts of classical (CD14(++)CD16(-)) monocytes, and decreased percentages of nonclassical (CD14(+)CD16(++)) monocytes. Patients with high disease activity had lower HLA DR expression on classical monocytes compared to low disease activity patients. There were no differences in monocyte subsets between subjects with DAS > 5.1 and DAS ≤ 5.1. There were no significant intergroup differences in IMT and the majority of classical CV risk factors. CONCLUSIONS: Patients with RA of short duration show alteration in peripheral blood monocyte subsets despite the fact that there is no evidence of subclinical atherosclerosis. Disease activity assessed with DAS28 was associated with impaired functional properties but not with a shift in monocyte subpopulations.
22798566 Very early rheumatoid arthritis as a predictor of remission: a multicentre real life prosp 2013 Jun BACKGROUND: To assess whether, in the real world of three early arthritis clinics, early referral could allow the best outcome, ie, remission, to be reached, and whether reaching the outcome was more dependent on therapy than on disease duration or vice versa. METHODS: 1795 patients with early arthritis (symptom duration≤12 months) were entered into a prospective follow-up study. 711 patients (39.6%) were diagnosed with rheumatoid arthritis (RA). Each RA patient was treated according to the local algorithm, in three tertiary referral centres (representing a small province, a medium sized province and a metropolitan area, respectively). Remission, defined using the disease activity score in 28 joints (DAS28<2.6) and American College of Rheumatology (ACR) criteria, was the major outcome evaluated at the 12-month follow-up. RESULTS: DAS28 remission was achieved in 34.3% (range 19.5-49%) of RA patients and ACR remission in 15.2% (range 8.5-20.6%). At the multivariate logistic regression analysis only two variables emerged as predictors of the major outcome: being in very early rheumatoid arthritis (VERA; less than 12 weeks symptom duration at the time of first treatment) and being on disease-modifying antirheumatic drugs (DMARD) within 3 months from disease onset. Among RA patients in remission, only 10% of VERA subjects received an anti-TNF blocker compared with 32.2% of non-VERA patients (p=0.002, OR 0.23, 95% CI 0.09 to 0.64). CONCLUSIONS: In a real-world setting, the 12 weeks disease duration and an early intervention with DMARD represent the most significant opportunities to reach the major outcome, ie, remission of RA. Moreover, VERA represents a window of opportunity in terms of cost saving.
24361610 Effect of TNFα on osteoblastogenesis from mesenchymal stem cells. 2014 Mar BACKGROUND: Bone destruction and osteoporosis are accelerated in chronic inflammatory diseases, such as rheumatoid arthritis (RA) and periodontitis, in which many studies have shown the proinflammatory cytokines, especially TNFα, play an important role; TNFα causes osteoclast-induced bone destruction as well as the inhibition of osteoblastogenesis. SCOPE OF REVIEW: Here we review our current understanding of the mechanism of the effect of TNFα on osteoblastogenesis from mesenchymal stem cells (MSCs). We also highlight the function of MSC in the pathogenesis of autoimmune diseases. MAJOR CONCLUSIONS: Many studies have revealed that TNFα inhibits osteoblastogenesis through several mechanisms. On the other hand, it has been also reported that TNFα promotes osteoblastogenesis. These discrepancies may depend on the cellular types, the model animals, and the timing and duration of TNFα administration. GENERAL SIGNIFICANCE: A full understanding of the role and function of TNFα on osteoblastogenesis from MSC may lead to targeted new therapies for chronic inflammation diseases, such as RA and periodontitis.
24708605 Effects of exercise on depressive symptoms in adults with arthritis and other rheumatic di 2014 Apr 7 BACKGROUND: Depression is a major public health problem among adults with arthritis and other rheumatic disease. The purpose of this study was to conduct a systematic review of previous meta-analyses addressing the effects of exercise (aerobic, strength or both) on depressive symptoms in adults with osteoarthritis, rheumatoid arthritis, fibromyalgia and systemic lupus erythematous. METHODS: Previous meta-analyses of randomized controlled trials were included by searching nine electronic databases and cross-referencing. Methodological quality was assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) Instrument. Random-effects models that included the standardized mean difference (SMD) and 95% confidence intervals (CIs) were reported. The alpha value for statistical significance was set at p ≤ 0.05. The U3 index, number needed to treat (NNT) and number of US people who could benefit were also calculated. RESULTS: Of the 95 citations initially identified, two aggregate data meta-analyses representing 6 and 19 effect sizes in as many as 870 fibromyalgia participants were included. Methodological quality was 91% and 82%, respectively. Exercise minus control group reductions in depressive symptoms were found for both meta-analyses (SMD, -0.61, 95% CI, -0.99 to -0.23, p = 0.002; SMD, -0.32, 95% CI, -0.53 to -0.12, p = 0.002). Percentile improvements (U3) were equivalent to 22.9 and 12.6. The number needed to treat was 6 and 9 with an estimated 0.83 and 0.56 million US people with fibromyalgia potentially benefitting. CONCLUSIONS: Exercise improves depressive symptoms in adults with fibromyalgia. However, a need exists for additional meta-analytic work on this topic.
25086074 Bone structure and perfusion quantification of bone marrow edema pattern in the wrist of p 2014 Sep OBJECTIVE: To quantify bone structure and perfusion parameters in regions of bone marrow edema pattern (BMEP), non-edematous bone marrow (NBM), and pannus tissue areas in the wrists of patients with rheumatoid arthritis (RA) using 3-Tesla (3T) magnetic resonance imaging (MRI), and high resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: Sixteen subjects fulfilling American College of Rheumatology classification were imaged using a HR-pQCT system and a 3T MRI scanner with an 8-channel wrist coil. Coronal T2-weighted and dynamic contrast-enhanced (DCE-MRI) images were acquired. BMEP and pannus tissue areas were segmented semiautomatically in T2-weighted images. NBM areas were placed at a similar distance from the joint space as BMEP regions. MR and HR-pQCT images were registered, and bone variables were calculated within the BMEP and NBM regions. Perfusion parameters in BMEP, pannus tissue, and NBM regions were calculated based on the signal-time curve obtained from DCE-MRI. RESULTS: Eighteen BMEP areas were segmented, 15 of them presented proximal to pannus-filled erosions. Significant increases in bone density and trabecular thickness and number were observed in all BMEP regions compared to NMB (p < 0.05). Significantly elevated perfusion measures were observed in both BMEP and pannus tissue regions compared to NBM (p < 0.05). CONCLUSION: BMEP regions showed significantly increased bone density and structures as well as perfusion measures, suggesting bone remodeling and active inflammation. Combining MRI and HR-pQCT provides a powerful multimodality approach for understanding BMEP and erosions, and for potentially identifying novel imaging markers for disease progression in RA.
24274618 Immune responses to stress after stress management training in patients with rheumatoid ar 2013 INTRODUCTION: Psychological stress may alter immune function by activating physiological stress pathways. Building on our previous study, in which we report that stress management training led to an altered self-reported and cortisol response to psychological stress in patients with rheumatoid arthritis (RA), we explored the effects of this stress management intervention on the immune response to a psychological stress task in patients with RA. METHODS: In this study, 74 patients with RA, who were randomly assigned to either a control group or a group that received short stress management training, performed the Trier Social Stress Test (TSST) 1 week after the intervention and at a 9-week follow-up. Stress-induced changes in levels of key cytokines involved in stress and inflammatory processes (for example, interleukin (IL)-6 and IL-8) were assessed. RESULTS: Basal and stress-induced cytokine levels were not significantly different in patients in the intervention and control groups one week after treatment, but stress-induced IL-8 levels were lower in patients in the intervention group than in the control group at the follow-up assessment. CONCLUSIONS: In line with our previous findings of lower stress-induced cortisol levels at the follow-up of stress management intervention, this is the first study to show that relatively short stress management training might also alter stress-induced IL-8 levels in patients with RA. These results might help to determine the role of immunological mediators in stress and disease. TRIAL REGISTRATION: The Netherlands National Trial Register (NTR1193)
23710573 Catabolic and anabolic periarticular bone changes in patients with rheumatoid arthritis: a 2013 INTRODUCTION: The aim of this study was to determine the factors, including markers of bone resorption and bone formation, which determine catabolic and anabolic periarticular bone changes in patients with rheumatoid arthritis (RA). METHODS: Forty RA patients received high-resolution peripheral quantitative computed tomography (HR-pQCT) analysis of the metacarpophalangeal joints II and III of the dominantly affected hand at two sequential time points (baseline, one year follow-up). Erosion counts and scores as well as osteophyte counts and scores were recorded. Simultaneously, serum markers of bone resorption (C-terminal telopeptide of type I collagen (CTX I), tartrate-resistant acid phosphatase 5b (TRAP5b)), bone formation (bone alkaline phosphatase (BAP), osteocalcin (OC)) and calcium homeostasis (parathyroid hormone (PTH), 25-hydroxyvitamin D3 (Vit D)) were assessed. Bone biomarkers were correlated to imaging data by partial correlation adjusting for various demographic and disease-specific parameters. Additionally, imaging data were analyzed by mixed linear model regression. RESULTS: Partial correlation analysis showed that TRAP5b levels correlate significantly with bone erosions, whereas BAP levels correlate with osteophytes at both time points. In the mixed linear model with erosions as the dependent variable, disease duration (P <0.001) was the key determinant for these catabolic bone changes. In contrast, BAP (P = 0.001) as well as age (P = 0.018), but not disease duration (P = 0.762), were the main determinants for the anabolic changes (osteophytes) of the periarticular bone in patients with RA. CONCLUSIONS: This study shows that structural bone changes assessed with HR-pQCT are accompanied by alterations in systemic markers of bone resorption and bone formation. Besides, it can be shown that bone erosions in RA patients depend on disease duration, whereas osteophytes are associated with age as well as serum level of BAP. Therefore, these data not only suggest that different variables are involved in formation of bone erosions and osteophytes in RA patients, but also that periarticular bone changes correlate with alterations in systemic markers of bone metabolism, pointing out BAP as an important parameter.
23778340 Expression of leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) on osteoclasts 2013 Apr OBJECTIVE: Leukocyte-associated immunoglobulin-like receptor-1 is an inhibitory receptor primarily expressed by immune cells. This study was undertaken to define the role of this molecule in osteoclast differentiation and rheumatoid arthritis. METHODS: In vitro osteoclast assays were performed to characterize the role of Leukocyte-associated immunoglobulin-like receptor-1 in murine and human osteoclastogenesis. Human Leukocyte-associated immunoglobulin-like receptor-1 expression was assessed by immunohistochemistry staining in the synovium of patients with rheumatoid arthritis. The levels of soluble Human Leukocyte-associated immunoglobulin-like receptor-1 were determined by enzyme-linked immunosorbent assay. RESULTS: We found that multinucleated osteoclast formation from mouse bone marrow cells was inhibited by treatment with a monoclonal antibody against mouse Leukocyte-associated immunoglobulin-like receptor-1 in vitro. By immunohistochemistry, we found that Leukocyte-associated immunoglobulin-like receptor-1 was mainly expressed by macrophages in the inflamed synovial tissue of rheumatoid arthritis patients. In addition, serum and synovial fluid levels of soluble Leukocyte-associated immunoglobulin-like receptor-1 were higher in rheumatoid arthritis patients compared to healthy controls or osteoarthritis patients. Moreover, overexpression of Leukocyte-associated immunoglobulin-like receptor-1 in CD14+ monocytes from healthy volunteers also inhibited human osteoclastogenesis. CONCLUSION: Collectively, these data demonstrate for the first time that Leukocyte-associated immunoglobulin-like receptor-1 inhibits osteoclastogenesis. Therefore, these results may have therapeutic implications for the treatment of rheumatoid arthritis.