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ID PMID Title PublicationDate abstract
17293363 Endothelial progenitor cells in active rheumatoid arthritis: effects of tumour necrosis fa 2007 Oct OBJECTIVES: To study the effects of short-term intermediate dose glucocorticoid (GC) therapy in patients with active rheumatoid arthritis (RA) on circulating endothelial progenitor cells (EPC), which are known to influence cardiovascular risk, and to elucidate mechanisms potentially responsible for the reduction of EPCs in patients with active RA. METHODS: EPCs were quantified in 29 patients with active RA by flow cytometry, colony forming unit (CFU) and circulating angiogenic cell (CAC) assays before and after 7 days of intermediate dose GC therapy. CFU from patients with RA and from healthy referents (HR) were cultured in vitro in the absence or presence of dexamethasone (Dex) and/or TNF. RESULTS: After 1 week of GC therapy, EPC increased from 0.026 (SD 0.003)% to 0.053 (SD 0.010)% (p<0.01), and from 12 (SD 4) to 27 (SD 7) CFU/well (p<0.02); CAC also increased from 7 (SD 2) to 29 (SD 8) cells/high power field (p<0.05). In parallel, disease activity decreased significantly after GC treatment. TNF serum levels also decreased from 36 (SD 10) to 14 (SD 6) pg/ml (p<0.0001). Addition of Dex to the RA CFU led to a significant increase of mean CFU counts, whereas addition of TNF induced a decrease of CFU. CONCLUSIONS: Our data indicate that TNF may be at least partly responsible for the reduction of EPC seen in patients with RA. Intermediate doses of GCs for a short period of time, apart from reducing disease activity, significantly increase circulating EPC.
17584584 MYO9B gene polymorphisms are associated with autoimmune diseases in Spanish population. 2007 Jul The aim of the study was to test MYO9B gene polymorphisms for association with three autoimmune diseases, systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and celiac disease (CD), in a Spanish population. We analyzed three SNPs (rs2305767, rs1457092, and rs2305764) in a case-control cohort composed of 349 SLE patients, 356 RA patients, 90 CD patients, and 345 healthy controls. All three SNPs showed a consistent increased frequency of the A allele in SLE, RA, and CD patients compared with healthy controls. An association was observed between CD and rs2305764 (p=0.01, OR=2.3), between SLE and rs1457092 (p=0.002, OR=1.4), and between RA and rs1457092 (p=0.02, OR=1.3). The three autoimmune diseases combined showed significant association with rs1457092 and rs2305764 and with the AAA haplotype (p haplotype=0.005, OR=1.3). Our data demonstrate consistent association with the A allele and AAA haplotype of three SNPs in the MYO9B gene, which were previously reported to be associated with CD in the Dutch population. This suggests that genetic variation in MYO9B is associated with CD, SLE, and RA and that MYO9B is a general risk factor for autoimmunity.
16855150 Inflammation and sex hormone metabolism. 2006 Jun The incidence of autoimmune diseases is higher in females than in males. In both sexes, adrenal hormones, that is, glucocorticoids, dehydroepiandrosterone (DHEA), and androgens, are inadequately low in patients when compared to healthy controls. Hormonally active androgens are anti-inflammatory, whereas estrogens are pro-inflammatory. Therefore, the mechanisms responsible for the alterations of steroid profiles in inflammation are of major interest. The local metabolism of androgens and estrogens may determine whether a given steroid profile found in a subject's blood results in suppression or promotion of inflammation. The steroid metabolism in mixed synovial cells, fibroblasts, macrophages, and monocytes was assessed. Major focus was on cells from patients with rheumatoid arthritis (RA), while cells from patients with osteoarthritis served as controls. Enzymes directly or indirectly involved in local sex steroid metabolism in RA are: DHEA-sulfatase, 3beta-hydroxysteroid dehydrogenase, 17beta-hydroxysteroid dehydrogenase, and aromatase (CYP19), which are required for the synthesis of sex steroids from precursors, 5alpha-reductase and 16alpha-hydroxylase, which can be involved either in the generation of more active steroids or in the pathways leading to depletion of active hormones, and 3alpha-reductase and 7alpha-hydroxylase (CYP7B), which unidirectionally are involved in the depletion of active hormones. Androgens inhibit aromatization in synovial cells when their concentration is sufficiently high. As large amounts of estrogens are formed in synovial tissue, there may be a relative lack of androgens. Production of 5alpha-reduced androgens should increase the local anti-inflammatory activity; however, it also opens a pathway for the inactivation of androgens. The data discussed here suggest that therapy of RA patients may benefit from the use of nonaromatizable androgens and/or the use of aromatase inhibitors.
16508932 Infliximab treatment maintains employability in patients with early rheumatoid arthritis. 2006 Mar OBJECTIVE: To evaluate the impact of infliximab therapy on the employment status of patients with early rheumatoid arthritis (RA). METHODS: Methotrexate (MTX)-naive patients with active early RA were randomly allocated to receive MTX plus placebo or MTX plus infliximab (3 mg/kg or 6 mg/kg) at weeks 0, 2, and 6 and then every 8 weeks through week 46. Data for patients younger than age 65 years were included in the analyses. A patient was categorized as employable if he or she was employed or felt well enough to work if a job were available. RESULTS: The change in actual employment was not significantly different between patients receiving MTX plus infliximab and those receiving MTX plus placebo (0.5% versus 1.3%; P > 0.5). However, the proportion of patients whose status changed from employable at baseline to unemployable at week 54 was smaller in the group receiving MTX plus infliximab compared with that in the group receiving MTX alone (8% versus 14%; P = 0.05). Patients who were treated with infliximab plus MTX had a significantly greater likelihood of improvement rather than deterioration in employability (odds ratio 2.4; P < 0.001); this likelihood was not significantly greater in patients receiving MTX alone. The proportion of employed patients who lost workdays during the trial was smaller in the MTX plus infliximab group than in the MTX-alone group (P = 0.010). CONCLUSION: The actual employment rates among patients in the 2 treatment groups were not different. However, patients with early RA who were treated with MTX plus infliximab had a higher probability of maintaining their employability compared with those who were treated with MTX alone.
16689999 Relevance of the stroma and epithelial-mesenchymal transition (EMT) for the rheumatic dise 2006 Epithelial-mesenchymal transition (EMT) is a term applied to the process whereby cells undergo a switch from an epithelial phenotype with tight junctions, lateral, apical, and basal membranes, and lack of mobility into mesenchymal cells that have loose interactions with other cells, are non-polarized, motile and produce an extracellular matrix. The importance of this process was initially recognized from a very early step in embryology, but more recently as a potential mechanism for the progression and spread of epithelial cancers. As the sequence of morphological changes has become understood in molecular terms, diseases characterized by alterations in stromal elements and fibrosis are being considered as examples of EMT. This review will focus on the pathogenetic features of immune-mediated renal disease, systemic sclerosis and rheumatoid arthritis that could be explained by EMT.
17652963 Signaling axis in osteoclast biology and therapeutic targeting in the RANKL/RANK/OPG syste 2007 Bone integrity is maintained through a balance between bone formation and bone resorption, and osteoclasts are primary cells involved in bone resorption. Recent studies have revealed an essential role of macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor kappa-B ligand (RANKL) in the development of osteoclasts, and detailed molecular cascades that induce osteoclast differentiation, activation and apoptosis have been clarified. Osteoclasts are involved in various pathologic conditions, such as osteoporosis, rheumatoid arthritis and tumor-induced bone disease, which are characterized by abnormal bone resorption, and the finding of RANKL has provided us a good therapeutic target for such pathologic conditions.
16507115 Enumeration and phenotypical analysis of distinct dendritic cell subsets in psoriatic arth 2006 Dendritic cells (DCs) comprise heterogeneous subsets of professional antigen-presenting cells, linking innate and adaptive immunity. Analysis of DC subsets has been hampered by a lack of specific DC markers and reliable quantitation assays. We characterised the immunophenotype and functional characteristics of psoriatic arthritis (PsA)-derived and rheumatoid arthritis (RA)-derived myeloid DCs (mDCs) and plasmacytoid DCs (pDCs) to evaluate their potential role in arthritis. Circulating peripheral blood (PB) pDC numbers were significantly reduced in PsA patients (P = 0.0098) and RA patients (P = 0.0194), and mDCs were significantly reduced in RA patients (P = 0.0086) compared with healthy controls. The number of circulating mDCs in RA PB was significantly inversely correlated to C-reactive protein (P = 0.021). The phenotype of both DC subsets in PsA PB and RA PB was immature as compared with healthy controls. Moreover, CD62L expression was significantly decreased on both mDCs (PsA, P = 0.0122; RA, P = 0.0371) and pDCs (PsA, P = 0.0373; RA, P = 0.0367) in PB. Both mDCs and pDCs were present in PsA synovial fluid (SF) and RA SF, with the mDC:pDC ratio significantly exceeding that in matched PB (PsA SF, P = 0.0453; RA SF, P = 0.0082). pDCs isolated from RA SF and PsA SF displayed an immature phenotype comparable with PB pDCs. RA and PsA SF mDCs, however, displayed a more mature phenotype (increased expression of CD80, CD83 and CD86) compared with PB mDCs. Functional analysis revealed that both SF DC subsets matured following toll-like receptor stimulation. pDCs from PB and SF produced interferon alpha and tumour necrosis factor alpha on TLR9 stimulation, but only SF pDCs produced IL-10. Similarly, mDCs from PB and SF produced similar tumour necrosis factor alpha levels to TLR2 agonism, whereas SF mDCs produced more IL-10 than PB controls. Circulating DC subset numbers are reduced in RA PB and PsA PB with reduced CD62L expression. Maturation is incomplete in the inflamed synovial compartment. Immature DCs in SF may contribute to the perpetuation of inflammation via sampling of the inflamed synovial environment, and in situ presentation of arthritogenic antigen.
16583470 Paraarticular trabecular bone loss at the ultradistal radius and increased arterial stiffe 2006 Apr OBJECTIVE: We recently reported enhanced arterial thickening in patients with rheumatoid arthritis (RA) and the importance of increased bone resorption in this process. Our aim was to examine whether arterial stiffening, another aspect of atherosclerosis, is also increased in patients with RA, and to determine if it is an important risk factor. METHODS: The subjects were 47 patients with RA and 49 healthy controls, all postmenopausal women. Subjects having risk factors for atherosclerosis were excluded. Femoral-ankle (fa) pulse wave velocity (PWV) and brachial-ankle (ba) PWV were measured in all patients using a waveform analyzer. Bone mineral density (BMD) at the ultradistal radius was assessed by peripheral quantitative computed tomography. Inflammation markers (C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, platelet count) and bone resorption markers (urinary excretion of deoxypyridinoline and N-terminal telopeptide) were also measured. RESULTS: The median values of faPWV and baPWV in RA patients were 1124 cm/s [interquartile range (IQR) 1040-1175] and 1539 cm/s (IQR 1297-1738), respectively, which were significantly greater than the respective values of 982 cm/s (IQR 819-1054; p < 0.001) and 1322 cm/s (IQR 1112-1398; p = 0.004) in controls. In multiple regression analysis, the presence of RA emerged as an independent factor associated with the greater faPWV and baPWV when adjusted for age, blood pressure, and smoking. In RA patients alone, BMD in the trabecular bone component, but not for the total bone (cortical plus trabecular), at the ultradistal radius correlated significantly with both faPWV and baPWV. Multiple regression analysis showed that trabecular BMD at the distal radius was a significant factor independently associated with greater faPWV and baPWV when adjusted for age, blood pressure, and smoking. None of the measured inflammation markers or bone resorption markers correlated with either faPWV or baPWV in patients with RA. CONCLUSION: Patients with RA show increased arterial stiffening, in addition to the arterial thickening we have previously reported, supporting the notion of enhanced atherosclerosis in RA patients. Paraarticular bone loss in the trabecular bone component at the ultradistal radius is a factor significantly associated with increased arterial stiffening in RA patients.
17591585 Disseminated cryptococcosis initially presenting as cellulitis in a rheumatoid arthritis p 2007 Jun Infection with Cryptococcus neoformans often occurs in immunocompromised hosts. It is usually acquired by invasion of the respiratory tract, and then the organisms may spread hematogenously to other viscera, mainly the central nervous system. Although there are some reports of primary cutaneous cryptococcosis, cryptococcal skin disease is a rare feature of disseminated cryptococcosis, and has a poor outcome if unrecognized and untreated. We present a case of cryptococcal cellulitis in a patient with rheumatoid arthritis who was receiving long-term steroid treatment. Reviewing the literature, this is the first report of rheumatoid arthritis with disseminated cryptococcosis initially presenting as cellulitis.
17453718 Gene expression profiling in autoimmune diseases: chronic inflammation or disease specific 2007 May A central issue in autoimmune disease is whether the underlying inflammation is a repeated stereotypical process or whether disease specific gene expression is involved. To shed light on this, we analysed whether genes previously found to be differentially regulated in rheumatoid arthritis (RA) patients and healthy individuals were specific for the arthritic process or likewise altered in other chronic inflammatory diseases such as chronic autoimmune thyroiditis (Hashimoto's thyroiditis, HT) and inflammatory bowel disease (IBD). Using qPCR for 18 RA-discriminative genes, there were no significant differences in peripheral blood mononuclear cell (MNC) gene expression patterns between 15 newly diagnosed HT patients and 15 matched healthy controls. However, the MNC expression levels of five genes were significantly upregulated in 25 IBD patients, compared to 18 matched healthy controls (CD14, FACL2, FCN1, RNASE2, VNN2). There was concordance in the directional change for all genes between IBD and RA patients, i.e. increased expression compared to controls. These data show that one third of the genes significantly upregulated in MNC from RA patients were upregulated in patients with other chronic immunoinflammatory diseases, but only if accompanied by pronounced systemic manifestations. This suggests that at least some of the genes activated in RA are predominantly or solely related to general and disease-nonspecific autoimmune processes.
18092263 Accumulation of FoxP3-expressing CD4+CD25+ T cells with distinct chemokine receptors in sy 2007 Nov OBJECTIVE: To explore the presence and characteristics of FoxP3-expressing CD4+CD25+ regulatory T cells in synovial fluid (SF) of patients with active rheumatoid arthritis (RA). METHODS: The frequency and chemokine receptors expression profile of FoxP3-expressing CD4+CD25+ regulatory T cells in SF and peripheral blood (PB) from RA patients and PB from healthy controls were investigated by flow cytometry using three- or four-colour intracellular staining. RESULTS: The frequency of CD4+CD25+ FoxP3+ T cells was increased significantly in SF compared with paired PB from RA patients and PB from healthy controls (p<0.05). However, the frequency in PB from RA patients was significantly lower than in PB from healthy controls (p<0.05). Notably, CD4+CD25+FoxP3+ T cells in SF expressed increased levels of inflammation-related trafficking chemokine receptors, such as CCR4, CCR5, and CXCR4. CONCLUSION: There is an accumulation of FoxP3-expressing regulatory T cells in RA SF, and such recruitment may be dependent on the distinct chemokine receptors expressed on regulatory T cells.
17143590 Combination therapy with cyclosporine A and anti-TNF-alpha agents in the treatment of rheu 2007 Jul We describe two cases of rheumatoid arthritis (RA) patients and concomitant hepatitis C virus infection (HCV), treated with cyclosporine A (CsA) and anti-TNF-alpha agents. SGOT/SGPT and HCV-RNA serum levels remained unchanged longer than 1 year of treatment. No side effects were registered. We suggest that combination therapy with CsA and TNF-alpha blockers should be considered safe and well-tolerated in the treatment of HCV-positive RA patients.
19067499 Impact of specialty drugs on the use of other medical services. 2008 Dec OBJECTIVE: To examine whether initiation of a biologic agent to treat 2 autoimmune disorders -- rheumatoid arthritis (RA) and multiple sclerosis (MS) -- affects use of other medical services. STUDY DESIGN: Longitudinal analysis from 1997 to 2005 examining linked pharmacy and medical claims from large, private employers. METHODS: The study sample included 30,761 individuals newly diagnosed with RA (92,660 person-years) and 8961 unique individuals with MS (25,100 person-years). Negative binomial models were used to estimate changes in inpatient, outpatient, and procedure use before and after initiating a biologic drug for each condition. RESULTS: Starting a biologic response modifier was associated with a reduction in physician visits and use of expensive procedures for patients with RA within 2 to 3 years of initiation. Use of immunomodulatory therapy for MS was associated with a reduced number of hospitalizations and expensive procedures within 2 years of initiation. Although biologics may reduce other types of service use, the savings do not come close to offsetting the full cost of these drugs. CONCLUSIONS: Given the high cost of many specialty drugs, health plans may rightly focus on making sure only patients who will most benefit receive them. But once such patients are identified, it makes little sense to limit coverage.
17728506 Ultrasonographic findings of the shoulder in patients with rheumatoid arthritis and compar 2007 Aug The objectives of this study were: 1) to identify the ultrasonographic (US) abnormalities and 2) to compare the findings of physical examination with US findings in rheumatoid arthritis (RA) patients with shoulder pain. We studied 30 RA patients. Physical examination was performed systemically as follows: 1) area of tenderness; 2) range of passive and active shoulder motion; 3) impingement tests; 4) maneuvers for determining the location of the tendon lesions. US investigations included the biceps, the supraspinatus, infraspinatus, and subscapularis tendons; the subacromial-subdeltoid bursa; and the glenohumeral and acromioclavicular joints. Thirty RA patients with 35 painful and 25 non-painful shoulders were examined. The range of motion affected the most by shoulder pain was abduction. The most frequent US finding of shoulder joint was effusion in the long head of the biceps tendon. Among the rotator cuff tendons, subscapularis was the most frequently involved. Tendon tear was also common among non-painful shoulders. Physical examination used for the diagnosis of shoulder pain had low sensitivity and specificity for detecting abnormalities in the rheumatoid shoulder joint. In conclusion, US abnormalities showed frequent tendon tears in our RA patients. Physical examination had low sensitivity and specificity for detecting rotator cuff tear in the rheumatoid shoulder joint.
17604848 Macrophages express granzyme B in the lesion areas of atherosclerosis and rheumatoid arthr 2007 Jul 31 Granzyme B is a major mediator of the cytotoxic immune response by inducing target cell death when internalized in the presence of perforin. Recently, several studies have focused on another role of granzyme B, which is extracellular matrix (ECM) remodeling through the degradation of ECM proteins. In order to investigate the expression pattern of granzyme B in the lesion areas of atherosclerosis and rheumatoid arthritis, we performed immunohistochemistry and in situ hybridization analyses using human atherosclerotic plaques and the synovial tissues of rheumatoid arthritic- and osteoarthritic-joints. In atherosclerotic plaques, granzyme B was expressed by macrophages in areas such as the boundary regions between media and intima, areas around necrotic cores, and in shoulder regions. In the synovial tissues of rheumatoid arthritic-joints, the expression of granzyme B was strongly observed in the lining layers where the majority of cells are macrophages and also in perivascular areas where macrophages and a small number of lymphocytes were mixed to form diffuse cellular aggregates. Granzyme B-positive cells were not detected in osteoarthritic synovium. Furthermore, the expression of granzyme B has been induced in the human macrophage cell line, THP-1, by ECM proteins or agents which induce macrophage differentiation. These observations indicate that macrophages should be added to the list of cell types that express granzyme B in human inflammatory diseases and that granzyme B may play a role in macrophage functions that are associated with disease progression.
16960929 Value of the HLA-DRB1 shared epitope for predicting radiographic damage in rheumatoid arth 2006 Dec OBJECTIVE: To investigate the influence of individual patient risk profiles on the value of the HLA-DRB1 shared epitope (SE) as a predictor of severe erosive damage in rheumatoid arthritis (RA). METHODS: Patient characteristics, clinical signs and symptoms, rheumatoid factor (RF) status, and HLA-DRB1 genotypes were available for 154 Caucasian women with RA. Risk profiles were defined by non-genetic factors that predict severe erosive disease. The additional value of the SE was defined by the likelihood ratios (LR) of SE presence and absence, which were calculated at the individual patient level. RESULTS: In the total population, the LR of SE presence was 1.42 and the LR of SE absence was 0.37, corresponding to an odds ratio of 3.9, indicating a substantially higher risk of severe erosive disease in those with the SE compared to those without. The LR of SE presence and absence varied depending on the risk profile of the women, from 1.01 to 2.25 for SE presence and 0.22 to 0.49 for SE absence. Considering all the patient characteristics, SE status was most significantly related to RF status. Consequently, the LR of SE presence and absence were higher for RF-negative women compared to RF-positive women (SE presence 1.77 vs 1.40, p < 0.001 and SE absence 0.38 vs 0.30, p < 0.001). CONCLUSION: The additional value of SE testing for predicting severe erosive disease varies according to patient risk profiles. Given the likely availability of genetic and other novel tests in the future, information about the additional value of test results is needed to ensure the optimal use of such testing in the management of RA.
16572448 Regulatory role of heme oxygenase 1 in inflammation of rheumatoid arthritis. 2006 Apr OBJECTIVE: To examine the expression and pathogenetic roles of heme oxygenase 1 (HO-1), an inducible heme-degrading enzyme with antiinflammatory properties, in rheumatoid arthritis (RA). METHODS: HO-1 expression in synovial tissue from patients with RA, patients with osteoarthritis, and patients with noninflammatory joint diseases was determined by immunoblotting and immunohistochemistry. Effects of various agents, such as hemin (a chemical inducer of HO-1), small interfering RNA (siRNA) specific for HO-1, HO-1 expression vector, and antirheumatic agents, on HO-1 expression in RA synovial cell lines were analyzed by real-time reverse transcription-polymerase chain reaction (PCR) and immunoblotting. Cytokine synthesis was evaluated by real-time PCR and enzyme-linked immunosorbent assay. RESULTS: HO-1 was expressed more abundantly in the lesions of synovial tissue from patients with RA than in those from the other patient groups. Hemin, auranofin, and HO-1 expression vector induced HO-1 and reduced expression of tumor necrosis factor alpha (TNFalpha) messenger RNA, lipopolysaccharide (LPS)-induced secretion of interleukin-6 (IL-6) and IL-8, and expression of cyclooxygenase 2 in the synovial cell lines. Treatment with HO-1-specific siRNA augmented the synthesis of TNFalpha, IL-6, and IL-8 and canceled the suppressive effects of auranofin on TNFalpha secretion. When hemoglobin, as a scavenger of carbon monoxide, was added to auranofin-treated synovial cell lines, LPS-dependent production of IL-6 and IL-8 was increased. CONCLUSION: Our data demonstrate that HO-1 is expressed in RA synovial tissues and plays a regulatory role in the development of inflammation. The pharmacologic effects of auranofin depend, in part, on the levels of HO-1, suggesting that HO-1 induction is a novel therapeutic strategy for RA.
18757243 Circulating levels of TNF-like cytokine 1A (TL1A) and its decoy receptor 3 (DcR3) in rheum 2008 Nov TL1A is a novel TNF-like cytokine, which provides co-stimulatory and Th1-polarizing signals to activated lymphocytes, via binding to death-domain receptor 3 (DR3). These functions are inhibited when TL1A associates to decoy receptor 3 (DcR3). We investigated the serum expression of TL1A and DcR3 in 81 patients with RA and 51 healthy controls. TL1A concentrations were elevated in patients by 5-fold (P<0.00001). This increase was more prominent in RFactor-positive patients and correlated with clinical activity in this subgroup. DcR3 was detected more frequently and in significantly higher values in RA-derived sera, correlated strongly with TL1A, and was present in inflammatory synovial fluid. Severe RA stage was associated with highly elevated TL1A and DcR3 serum levels. Treatment with an anti-TNF agent significantly decreased TL1A serum levels. We conclude that TL1A may serve as an inflammatory marker in RA. Interactions between TL1A and its receptors may be important in the pathogenesis of RA.
17324099 Attention to sex-related factors in the development of clinical practice guidelines. 2007 Jan BACKGROUND: Clinical practice guidelines describe optimal strategies for disease prevention, diagnosis, or treatment. Increasing evidence indicates that sex-related factors may have an impact on these strategies. We examined the way in which two Dutch guideline organizations address evidence on sex factors in their guideline development methodologies. We then determined whether attention to these factors could be improved and, if so, how this could be done. METHODS: We selected seven recent guidelines on four conditions: hypertension, depression, osteoporosis, and rheumatoid arthritis. We studied information obtained from interviews with members of the guideline committees and analyzed the content of the guideline documents themselves. Our findings were discussed at an expert meeting. RESULTS: We found that all the guideline committees concerned applied an internationally accepted framework for guideline development. The proportion of male members ranged from 67% to 100%. None of the guidelines included a question (or subquestion) focusing on sex-related factors. In the literature searches no sex-specific search terms were used. Critical appraisals did not include any systematic focus on sex-related factors or effects. The number of sex-specific recommendations (relative to the total number of recommendations) ranged from 0 of 82 and 0 of 148 in the guidelines on depression to 16 of 84 in one of the guidelines on osteoporosis. CONCLUSIONS: We found that when developing guidelines, none of the committees systematically focused on sex-related factors that might be relevant to the way in which evidence is identified, appraised, or described. A number of recommendations were made with the aim to facilitate greater attention to sex-related factors in the current methods of guideline development.
18480830 Differential expression of transcripts for the autoimmunity-related human dendritic cell i 2008 Jul Dendritic cell immunoreceptor (DCIR) deficiency is related to development of autoimmune disorders and DCIR gene polymorphisms are associated with rheumatoid arthritis (RA). We analyzed the mRNA expression from the four known transcripts of DCIR in IFN-gamma-treated human leukocytes together with fine mapping across the locus. RA patients and healthy controls were genotyped for several single nucleotide polymorphisms (SNPs) in DCIR and flanking regions. mRNA expression in peripheral blood mononuclear cells (PBMCs), stimulated with gamma-interferon (IFN-gamma) in vitro, was determined by transcript-specific PCR. Our data reveal that IFN-gamma significantly downregulates the average expression of transcripts DCIR_v1, DCIR_v2, DCIR_v3 and DCIR_v4 (P<0.0001 for v1, P<0.02 for v2, P<0.0001 for v3, P<0.001 for _v4, patients and controls, Wilcoxon signed-rank). The expression of DCIR showed significant association with variations in the gene. Cells with the RA-associated allele rs2024301 exhibit a significant increase in the expression of DCIR_v4. We also present a new fifth isoform lacking exons 2, 3 and 4. This data illustrate that common genetic variations may influence DCIR mRNA expression. We also show that the expression is regulated by the inflammatory mediator IFN-gamma, affecting all four transcripts and that this was independent of genotype.