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ID PMID Title PublicationDate abstract
20936980 Xenotropic murine leukemia virus-related virus prevalence in patients with chronic fatigue 2010 Nov 15 We investigated the prevalence of xenotropic murine leukemia virus-related virus (XMRV) among 293 participants seen at academic hospitals in Boston, Massachusetts. Participants were recruited from the following 5 groups of patients: chronic fatigue syndrome (n = 32), human immunodeficiency virus infection (n = 43), rheumatoid arthritis (n = 97), hematopoietic stem-cell or solid organ transplant (n = 26), or a general cohort of patients presenting for medical care (n = 95). XMRV DNA was not detected in any participant samples. We found no association between XMRV and patients with chronic fatigue syndrome or chronic immunomodulatory conditions.
19473574 Early improvement of health-related quality of life during treatment with etanercept and a 2009 Mar OBJECTIVES: To assess health-related quality of life (HRQoL) in patients with rheumatoid arthritis (RA) treated with etanercept or adalimumab in routine clinical practice. METHODS: Patients with RA who started etanercept or adalimumab at Helsinki University Central Hospital or Lappeenranta Central Hospital during 2003-2006 were asked to participate in the study. In 97 patients, HRQoL was measured by the RAND 36-Item Health Survey 1.0 (RAND-36) at baseline and after three months of the treatment. HRQoL of the RA patients was compared to the Finnish age- and sex-matched general population values. In addition, changes in clinical parameters and disability index measured by the health assessment questionnaire (HAQ) were recorded. RESULTS: Treatment with etanercept and adalimumab increased the values in all domains of the RAND-36 during the first three months in routine practice. The improvement in both groups was statistically significant: with etanercept p=0.041 and with adalimumab p=0.019. The efficacy of etanercept and adalimumab in improving HRQoL during the first three months was comparable. The patients reported their best improvement in the subscales of bodily pain, role functioning/physical, energy, social functioning, and role functioning/emotional. Compared to the Finnish age- and sex-matched general population values, the HRQoL of the patients with RA was significantly lower at baseline and remained low at follow-up. The change in clinical parameters and the HAQ paralleled the improvement in HRQoL. CONCLUSION: Treatment of patients with RA with etanercept and adalimumab in routine clinical practice provides clinically important and statistically significant improvement in HRQoL already in the first three months.
20173395 The first decade of biologic TNF antagonists in clinical practice: lessons learned, unreso 2010 Results from clinical trials of biologic anti-TNF drugs performed in the late 1990s confirmed the biological relevance of TNF function in the pathogenesis of chronic noninfectious inflammation of joints, skin and gut, which collectively affects 2-3% of the population. Up to April 2009, more than two million patients worldwide have received the first marketed drugs, namely the monoclonal anti-TNF antibodies infliximab and adalimumab and the soluble TNF receptor etanercept. All three are equally effective in rheumatoid arthritis, ankylosing spondylitis, psoriasis and psoriatic arthritis, but, for not clearly defined reasons, only the monoclonal antibodies are effective in inflammatory bowel disease. About 60% of patients who do not benefit from standard nonbiologic treatments for these diseases respond to TNF antagonists. Less than half of responding patients achieve complete remission of disease. Importantly, some of those patients with rheumatoid arthritis in whom long-term anti-TNF therapy induced disease remission remain disease-free after discontinuation of any kind of treatment. There are not yet reliable predictors of which patients will or will not respond on anti-TNF therapy, whereas subsequent loss of an initial clinical response occurs frequently. The spectrum of efficacy anti-TNF therapies widens to include diseases such as systemic vasculitis and sight-threatening uveitis. While paradoxical new adverse effects are recognized, i.e. exacerbation or development of new onset psoriasis, reactivation of latent tuberculosis remains the most important safety issue of anti-TNF therapies. Clinical practice guidelines and consensus statements on the criteria of introduction, duration of treatment and cessation of TNF antagonists, including safety issues, are under constant revision as data from longer periods of patient exposure accumulate. It is hoped that more efficacious drugs that will ideally target the deleterious proinflammatory properties of TNF without compromising its protective role in host defense and (auto)immunity will be available in the near future.
20661741 Influence of Rituximab on markers of bone remodeling in patients with rheumatoid arthritis 2011 Feb Immune system and bone are interacting in a complex way. Rheumatoid arthritis is characterized not only by joint destruction, but also by development of systemic osteopenia and osteoporosis. The CD20-depleting antibody Rituximab (Rtx) is a novel therapeutic option able significantly to slow the destructive joint process of rheumatoid arthritis. However, there are little data whether Rtx influences systemic bone remodeling. In the present prospective study, we evaluated the influence of Rtx on markers of bone metabolism with a follow-up of 3-15 months after Rtx therapy (2 dose of each 1,000 mg) in 13 patients with rheumatoid arthritis. There was no significant change of the bone formation markers bone alkaline phosphatase and c-terminal propeptide of collagen I. However, a non-significant tendency of decrease of RANKL (with no chance of osteoprotegerin) and a significant decrease of the bone degradation marker desoxypyridinolin crosslinked collagen I was observed 15 months after Rtx application. These initial results provide no evidence of a negative systemic influence of Rtx on bone remodeling. In contrast, it appears that Rtx lowered osteoclast activity often found increased in active rheumatoid arthritis contributing to osteoporosis in this disease.
20362898 Morphologic, functional, and occlusal characterization of mandibular lateral displacement 2010 Apr INTRODUCTION: Mandibular lateral displacement (MLD) is clinically characterized by deviation of the chin, facial asymmetry, dental midline discrepancy, crossbite in the posterior region, and high prevalence of internal derangement of the temporomandibular joint. Morphologic and functional characteristics of MLD should be clarified to correct and prevent this malocclusion. METHODS: We examined the morphologic features, occlusal scheme, and functional behavior of MLD in 116 patients. Facial morphology was examined with posteroanterior cephalograms, occlusion guidance on the articulator after face-bow transfer, and condylar movement with the condylograph. RESULTS: The superiorly inclined occlusal plane was associated with mandibular deviation in the same direction. The posterior occlusal plane on the shifted side was significantly steeper than that on the nonshifted side. Functional analysis of condylar movement showed a close relationship between the direction of MLD and the direction of condylar lateral shift during opening and closing, and protrusion and retrusion. The occlusal guidance inclination in the buccal segment of the nonshifted side was steeper than that in the shifted side. CONCLUSIONS: The results suggested that reduced vertical height of the dentition on 1 side induced mandibular lateral adaptation with contralateral condylar shift (asymmetry); this leads to condylar lateral shift during functional movement.
19758134 Circulating cardiac troponin-I autoantibodies in human plasma and serum. 2009 Sep We identified IgG reactive with human cardiac troponin-I (cTnI) in plasma and serum samples (N = 1930) from normal blood donors, and in sample cohorts characterized on the basis of clinical biomarkers associated with cardiac, infectious, and autoimmune diseases. cTnI and brain natriuretic peptide were the biomarkers chosen to reflect myocyte damage or left ventricular dysfunction, respectively. The infectious disease cohorts were serologically positive for antibodies to hepatitis B (natural infection), hepatitis C virus, and Chagas (i.e., T.cruzi). The autoimmune cohorts were represented by samples from diagnosed systemic lupus erythematosus (biomarker: dsDNA) and rheumatoid arthritis (biomarker: rheumatoid factor) subjects. The prevalence of IgG autoantibodies reactive with cTnI was high in the normal donor cohort (95/750, 12.7%). The prevalence in the other sample cohorts was not significantly different from that in the normal blood donors, with the exception of a slight increase in the rheumatoid factor cohort (28/137, 20.4%). The presence of anti-cTnI IgG in highly reactive samples was confirmed by inhibition with the antigen and further by screening with a library of peptides derived from the human cTnI amino acid sequence. Our data suggest that these autoantibodies are polyspecific, encompassing epitopes across the entire cTnI sequence, including the cardiac-specific amino terminal region.
19136742 Erythrocyte aggregation in rheumatoid arthritis: Cell and plasma factor's role. 2009 Increase in erythrocyte aggregation (EA) is pathognomonic for rheumatoid arthritis (RA), and its estimation through erythrocyte sedimentation rate (ESR) is part of DAS 28-4 activity diagnosis, with low correlation with EA and that does not discriminate the contribution of cell factors that increase aggregation. OBJECTIVE: To analyse cell and plasma factors that might be involved in EA increase, to understand how RA affects blood components, thus modifying blood fluid behavior. METHODOLOGY: One hundred women presenting active RA were compared with age-matched controls (C). EA was measured by transmitted light, obtaining two parameters: 2k2n0, characterizing the aggregation process kinetics and s0/n0, estimating aggregates size. Cell factors assays: erythrocyte deformability, by filtration through nucleopore membranes, cell shape, by microscopy, and membrane fluidity by EPR. Plasma: total proteins and CRP, albumin, fibrinogen (Fb), by gravimetry, and IgG and IgM by single radial immuno-diffusion. RESULTS: AR and C (x+/-SE). 2k2n0: 31.83+/-2.84, 23.75+/-1.91; s0/n0: 0.92+/-0.05, 0.87+/-0.04. Rigidity index (RI): 14.79+/-4.71, 6.92+/-1.31. Morphological index: 0.28+/-0.03, 0.30+/-0.05, n.s. Fb (mg/dl): 382+/-80, 299+/-70. IgG (mg/dl): 1580+/-219, 1296+/-158; IgM (mg/dl) 233+/-28, 183+/-23; albumin (g/dl) 3.84+/-0.44, 3.77+/-0.51 n.s. p<0.05 accepted. Correlations: 2k2n0 vs. Fb r=0.66; s0/n0 vs. Fb r=0.51; 2k2n0 vs. Igs r=0.65; s0/n0 vs. Igs r=0.56. 2k2n0 vs. RI r=-0.59; s0/n0 vs. RI=-0.52, p<0.05. CONCLUSIONS: Plasma factors, Igs and Fb increased aggregation, since RI is altered, this reduces the process efficiency regarding aggregation. Patients with active RA present an increased EA, with values modifications associated with the activity index DAS 28-4, thus becoming an RA activity indicator.
20516029 Canadian recommendations for use of methotrexate in patients with rheumatoid arthritis. 2010 Jul OBJECTIVE: To develop recommendations for the use of methotrexate (MTX) in patients with rheumatoid arthritis. METHODS: Canadian rheumatologists who participated in the international 3e Initiative in Rheumatology (evidence, expertise, exchange) in 2007-2008 formulated 5 unique Canadian questions. A bibliographic team systematically reviewed the relevant literature on these 5 topics. An expert committee consisting of 26 rheumatologists from across Canada was convened, and a set of recommendations was proposed based on the results of systematic reviews combined with expert opinions using a nominal group consensus process. RESULTS: The 5 questions addressed drug interactions, predictors of response, strategies to reduce non-serious side effects, variables to assess clinical response, and incorporating patient preference into decision-making. The systematic review retrieved 93 pertinent articles; this evidence was presented to the expert committee during the interactive workshop. After extensive discussion and voting, a total of 9 recommendations were formulated: 2 on drug interactions, 1 on predictors of response, 2 on strategies to reduce non-serious side effects, 3 on variables to assess clinical response, and 1 on incorporating patient preferences into decision-making. The level of evidence and the strength of recommendations are reported. Agreement among panelists ranged from 85% to 100%. CONCLUSION: Nine recommendations pertaining to the use of MTX in daily practice were developed using an evidence-based approach followed by expert/physician consensus with high level of agreement.
20367977 Screening disease-associated proteins from sera of patients with rheumatoid arthritis: a c 2010 Mar 5 BACKGROUND: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation at the synovial membrane. Although great progress has been made recently in exploring the etiology and pathogenesis of RA, its molecular pathological mechanism remains to be further defined and it is still a great challenge in determining the diagnosis and in choosing the appropriate therapy in early patients. This study was performed to screen candidate RA-associated serum proteins by comparative proteomics to provide research clues to early diagnosis and treatment of RA. METHODS: Sera isolated from 6 RA patients and 6 healthy volunteers were pooled respectively and high-abundance proteins were depleted by Plasma 7 Multiple Affinity Removal System. The protein expression profiles between the two groups were then compared by two-dimensional gel electrophoresis (2-DE) and the proteins over/under-expressed by more than 3-fold were identified by mass spectrometry analysis. To validate the differential expression levels of the identified proteins between the two groups, ELISA was performed in two of the identified proteins in individual sera from 32 RA patients and 32 volunteers. RESULTS: Eight proteins which over/under-expressed in sera of RA patients were identified. Among them, chain A of transthyretin (TTR) was under-expressed, while serum amyloid A protein, apolipoprotein A (ApoA)-IV, ApoA-IV precursor, haptoglobin 2, ceruloplasmin (Cp), immunoglobulin superfamily 22 and HT016 were over-expressed. ELISA test confirmed that Cp expressed remarkably higher while TTR obviously lower in RA group compared with volunteer group. CONCLUSION: There were 8 identified proteins differentially expressed between RA group and volunteer group, which might be candidate RA-associated proteins and might be promising diagnostic indicators or therapeutic targets for RA.
19404963 Cadherin 11 promotes invasive behavior of fibroblast-like synoviocytes. 2009 May OBJECTIVE: To define the expression pattern of cadherin 11 in the destructive pannus tissue of patients with rheumatoid arthritis, and to determine whether cadherin 11 expression in fibroblast-like synoviocytes controls their invasive capacity. METHODS: Cadherin 11 expression in rheumatoid synovial tissue was evaluated using immunohistochemistry. To examine the role of cadherin 11 in regulating the invasive behavior of fibroblast-like synoviocytes, we generated L cell clones expressing wild-type cadherin 11, mutant cadherin 11, and empty vector-transfected controls. The invasive capacity of L cell transfectants and cultured fibroblast-like synoviocytes treated with a blocking cadherin 11-Fc fusion protein or control immunoglobulin was determined in Matrigel invasion assays. RESULTS: Immunohistochemical analysis revealed that cadherin 11 is abundantly expressed in cells at the cartilage-pannus junction in rheumatoid synovitis. Assays to determine invasion demonstrated a 2-fold increased invasive capacity of cadherin 11-transfected L cells compared with L cells transfected with E-cadherin or control vector. The invasive behavior of L cells stably transfected with a cadherin 11 construct that lacked the juxtamembrane cytoplasmic domain was diminished to the level of vector control L cells. Furthermore, treatment with the cadherin 11-Fc fusion protein diminished the invasive capacity of fibroblast-like synoviocytes. CONCLUSION: The results of these in vitro studies implicate a role for cadherin 11 in promoting cell invasion and contribute insight into the invasive nature of fibroblast-like synoviocytes in chronic synovitis and rheumatoid arthritis.
20506563 Aberrant IgG galactosylation precedes disease onset, correlates with disease activity, and 2010 Aug OBJECTIVE: To examine the association between aberrant IgG galactosylation and disease parameters in rheumatoid arthritis (RA). METHODS: Analysis of N-glycan in serum samples from multiple cohorts was performed. The IgG N-glycan content and the timing of N-glycan aberrancy relative to disease onset were compared in healthy subjects and in patients with RA. Correlations between aberrant galactosylation and disease activity were assessed in the RA cohorts. The impact of disease activity, sex, age, anti-cyclic citrullinated peptide (anti-CCP) antibody titer, disease duration, and C-reactive protein level on aberrant galactosylation was determined using multivariate analysis. The N-glycan content was also compared between epitope affinity-purified autoantibodies and the remaining IgG repertoire in RA patients. RESULTS: Our results confirm the aberrant galactosylation of IgG in RA patients as compared with healthy controls (mean +/- SD 1.36 +/- 0.43 versus 1.01 +/- 0.23; P < 0.0001). We observed a significant correlation between levels of aberrant IgG galactosylation and disease activity (Spearman's rho = 0.37, P < 0.0001). This correlation was higher in women (Spearman's rho = 0.60, P < 0.0001) than in men (Spearman's rho = 0.16, P = 0.10). Further, aberrant IgG galactosylation substantially predated the onset of arthritis and the diagnosis of RA (3.5 years) and resided selectively in the anticitrullinated antigen fraction. CONCLUSION: Our findings identify aberrant IgG galactosylation as a dysregulated component of the humoral immune response in RA that begins prior to disease onset, associates with disease activity in a sex-specific manner, and resides preferentially in autoantibodies.
20822186 Mass spectrometric immunoassay for quantitative determination of protein biomarker isoform 2010 Nov 5 Protein biomarkers are essential in assessing pathogenic processes. The impetus for finding new biomarkers has been accelerated by the arrival of the "omics" technologies. However, equally important is the rediscovery of existing biomarkers with these new approaches as novel variants can be discovered that can improve their utility. Presented here is a mass spectrometric immunoassay method for quantitative determination of β-2-microglobulin, an established biomarker used in the diagnosis of active rheumatoid arthritis and kidney disease, and its structural variant, cleaved at and deficient in lysine-58 (ΔK58-b2m). β-Lactoglobulin was incorporated into the assay as an internal reference standard, serving as normalization point for β-2-microglobulin quantification. The precision, linearity, and recovery characteristics of the assay were established. The new assay was also benchmarked against existing β-2-microglobulin ELISA. The assay was utilized to determine the individual concentration of β-2-microglobulin and its variant across a larger cohort of samples, demonstrating the ability to simultaneously quantify both proteins.
19538103 Mechanisms underlying methotrexate-induced pulmonary toxicity. 2009 Jul BACKGROUND: Methotrexate (MTX) has been widely used for the treatment of inflammatory diseases and rheumatoid arthritis, as well as a variety of tumors. However, MTX-induced pulmonary toxicity is a serious and unpredictable side effect of the therapy, which includes allergic, cytotoxic or immunologic reactions, and is a major clinical problem. OBJECTIVE: To summarize the mechanisms of action involved in MTX-induced pulmonary toxicity. METHODS: We reviewed the literature describing MTX-induced adverse pulmonary effects and the mechanisms of action underlying MTX-induced pulmonary toxicity. CONCLUSION: The mechanisms underlying MTX toxicity are complex. The clinical effects may be attributable to both the anti-inflammatory and immunosuppressive effects of MTX. The mechanisms causing the side effects of MTX include mutation of the genotype, inhibition of transport, MTX-polyglutamates and P-glycoprotein binding with MTX. The p38 MAPK-signaling pathway is especially associated with a pulmonary inflammatory response. These mechanisms can be applied to optimize drug treatment.
21612052 [Dry eye syndrome--multispecialistic disease. Part one: Pathogenesis, signs, classificatio 2010 The authors presents the review of the literature concerning on the signs, classification, connections between the dry eye syndrome and other diseases and the risk factors of dry eye syndrome. It is a prevalent, multifactorial disease that is particularly frequent in elderly patients and women, especially in menopausal and postmenopausal period. Dry eye syndrome can be episodic with transient signs and symptoms or chronic with persistent signs and symptoms and is characterized by one or more of the following symptoms: burning, itching, foreign body sensation, soreness, dryness, photophobia, redness, and reduced visual acuity. The tear film instability of dry eye syndrome, which is accompanied by increased osmolarity of the tear film, causes inflammation and structural damage to the ocular surface. There are two major etiologic categories of dry eye syndrom: aqueous-deficient and evaporative. The most frequent classification of dry eye for practical clinical use is triple classification based on the ethiology, histopathological changes and severity of the disease.
19799204 [Clinical experience with infliximab administration in patients with rheumatoid arthritis 2009 AIM: To analyse the data on infliximab administration (efficacy, tolerance, toxicity) in patients with rheumatoid arthritis (RA) in Russia by clinical evidence provided by the multicenter observation trial. MATERIAL AND METHODS: The register included 297 patients with a documented diagnosis of RA who had for the first time treated with infliximab. The efficacy of the drug was evaluated by EULAR criteria based on the dynamics of DAS28 index. RESULTS: The results of infliximab treatment show good response of RA patients to standard courses of infliximab. A good/satisfactory effect by EULAR criteria was achieved in 80% patients to week 22 of therapy and in 85% to week 46. After 6-month (22 week) infliximab treatment a good effect was achieved in 15.7% patients, satisfactory--in 64.7%; 19.6% patients did not respond. Remission (DAS28 < 2.6 units) was achieved in 7% patients. Infliximab tolerance was satisfactory. Non-severe infusion reactions were most frequent unwanted effects. To treatment week 22, ten patients developed serious side effects causing the drug discontinuation. CONCLUSION: The results of the Russian register confirm a high therapeutic potential and satisfactory tolerance of infliximab observed in real rheumatological practice of the treatment of severe RA. These results agree with those of European registers of infliximab.
20435650 Discrepancies in categorizing rheumatoid arthritis patients by DAS-28(ESR) and DAS-28(CRP) 2010 Aug OBJECTIVES: The 28-joint disease activity score (DAS-28) guides the use of biologics in RA. The aims of this study were to investigate agreement between the ESR- and CRP-based DAS-28 definitions, and to examine how this agreement may be improved. METHODS: Data were obtained from registers of early (n = 520) and established RA (n = 364) patients. Agreement over disease activity levels (remission, low, moderate and high) at baseline and 6 months, and EULAR responder status at 6 months, were assessed in the early cohort. Two alternative DAS-28(CRP) definitions, obtained through linear regression analyses at baseline in the early RA patients, were validated with 6-month data from both the cohorts. RESULTS: In early RA patients, despite a high percentage of exact agreement over DAS-28 categories (88.2%), 38 (30.4%) of 125 patients with 'moderate' DAS-28(CRP) at baseline had 'high' DAS-28(ESR). This agreement was improved by modifying the DAS-28(CRP) definition, and by incorporating age and gender: e.g. in early RA patients with moderate original DAS-28(CRP), 30.4% had 'high' DAS-28(ESR), whereas 3.2% had 'low' DAS-28(ESR); following DAS-28(CRP) transformation both proportions were 6.6%. Incorporating age and gender did not improve agreement over EULAR response states. CONCLUSION: The DAS-28(ESR) and DAS-28(CRP) definitions differ substantially in classifying RA patients as having moderate or high disease activity, with the ESR definition resulting in a higher proportion of high DAS-28 especially in women. Our results suggest that modifying the DAS-28(CRP) definition may improve agreement with DAS-28(ESR). There are important implications for meta-analyses and for therapy driven by DAS scores.
19898778 The association between rheumatoid arthritis related structural changes in hands and compu 2010 Mar INTRODUCTION: This cross-sectional study examined the effect of structural changes caused by rheumatoid arthritis (RA) on computer keyboarding style to provide insights on how changes may affect worker performance. METHOD: Computer keyboarding styles, as measured by the keyboard-personal computer style instrument, were compared between 45 keyboard operators with RA and 29 without. A severity of structural changes score (SSCS) was assigned after recruitment by observing subjects' hands while operating a keyboard. Significant differences between each item of keyboarding style by diagnosis were identified through Chi square analyses. Logistic regression models with age, diagnosis, SSCS, and touch typing training as the predicators further evaluated the effect of structural changes on each item of personal keyboarding style. RESULTS: Significantly more keyboard operators with RA used high force keystrokes, did not use a wrist rest, moved their hands to strike keys, maintained their wrists and fingers in a fixed position and used fewer than two fingers to activate keys. The amount of variance explained by each model varied from 8 to 56%. SSCS was the most common predictor of keyboarding style (54% of significant models), followed by age (35% of significant models), diagnosis (19% of significant models), and touch typing training (15% of significant models). CONCLUSION: Severity of structural changes and age are significant predictors of keyboarding style for computer operators with RA. The keyboarding styles used by computer operators with RA appear to reduce typing productivity and have the potential to put stress on joints already affected by RA. Computer operators with RA may benefit from worksite modifications that address keyboarding style such as alternate keyboards.
19772806 Systematic review on the safety of methotrexate in rheumatoid arthritis regarding the repr 2009 Jul OBJECTIVE: To analyze the safety of methotrexate (MTX) in rheumatoid arthritis (RA) regarding the reproductive system (fertility, pregnancy, and breastfeeding). METHODS: Systematic review of studies retrieved by a sensitive search strategy in Medline (1961 - October 2007), Embase (1961 - October 2007), Cochrane Library (up to October 2007), and from the abstracts of the ACR (2005, 2006) and EULAR (2005 - 2007) annual scientific meetings. SELECTION CRITERIA: a) population: studies had to include patients with RA; b) intervention and control: discontinuation of MTX or elective abortion versus continuation of MTX or continuing pregnancy; and c) outcomes: infertility, oligospermia, reversibility, miscarriages, malformations, premature babies, healthy newborn, percent of the dose of MTX that passes to human milk, adverse effects in the lactating child. There was no limitation regarding study design, except for case reports, or language. RESULTS: MTX and pregnancy: we selected 6 articles for detailed evaluation from 847 initial ones from the literature search. They were descriptions of cases obtained from searching retrospectively clinical databases of individual centers or from surveys. Patients had been exposed to MTX at doses used in rheumatology (5-25 mg/w), from conception to first trimester of pregnancy. Total number of MTX exposed pregnancies is 101, and the pooled outcomes (elective abortion not included): 19 miscarriages (23% of pregnancies); 55 live births (66% of pregnancies); and 5 of them had minor neonatal malformations (5% of pregnancies). The rate of induced abortions is 18%. MTX and lactation and fertility: no articles fulfilled the selection criteria. There is indirect evidence on the excretion of MTX in human milk and probably of reversible infertility from case reports. CONCLUSIONS: This review exposes the shortage of data on the safety and risks of MTX during conception, pregnancy and lactation at the doses commonly used in rheumatology. MTX and pregnancy: there is not sufficient evidence to support whether it is MTX or the disease what underlies miscarriage in these patients. Pooling the data from the studies included, the rates of miscarriages and of birth defects are similar to the rates observed in healthy population. MTX and lactation and fertility: there is absence of confirming evidence.
20162315 Augmentation index in patients with rheumatoid arthritis and ankylosing spondylitis treate 2010 Jul Premature atherosclerosis is linked to inflammation. Arterial stiffness is a marker of vascular dysfunction. We tested the hypothesis that treatment with infliximab, which is effective in reducing inflammation in rheumatoid arthritis (RA) and ankylosing spondylitis (AS), also lowers the augmentation index (AIx) in patients with active disease. We also analyzed the subendocardial viability ratio (SEVR), which is a measure of myocardial perfusion relative to cardiac workload. Included in the study were 30 patients (17 RA, 13 AS). Conventional treatment failed in all patients. The AIx and SEVR were determined by radial applanation tonometry before and after treatment with infliximab, at baseline and at week 7. After treatment with infliximab, Disease Activity Score for 28 joints (RA patients), Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Functional Index (AS patients), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) improved significantly (p < 0.001). The AIx for all patients increased from 22.0 +/- 14.0% to 24.6 +/- 13.0% (p = 0.03). The increase in the RA sub-group (p = 0.01) was also significant. The SEVR decreased from 148.6 +/- 23.7% to 141.2 +/- 23.7% (p = 0.04). Infliximab did not reduce the AIx in patients with RA and AS, although there were clinical improvements and CRP and ESR decreased. Instead, the AIx increased. This could negatively influence cardiac workload.
20127215 Hsp40 proteins modulate humoral and cellular immune response in rheumatoid arthritis patie 2010 Sep Recent research on the heat shock proteins (Hsps) in chronic inflammatory diseases indicates that Hsps may have disease-suppressive activities. Our aim was to characterize immune response directed to bacterial (DnaJ) and human Hsp40s in patients with rheumatoid arthritis (RA). We found elevated levels of anti-DnaJ, anti-Hdj2, and anti-Hdj3 (but not ant-Hdj1) serum antibodies in the RA patients (P < or = 0.001) compared to healthy controls. In peripheral blood mononuclear cells (PBMCs) culture, all tested Hsp40 proteins significantly inhibited the divisions of CD4+ and CD8+ T cells of the RA patients but not those of the controls. Both DnaJ and Hdj2 stimulated secretion of the main anti-inflammatory cytokine IL-10 by PBMCs of the RA patients (P < 0.05), and of IL-6 by PBMCs of the RA (P < 0.001) and control (P < 0.01) groups. DnaJ reduced TNFalpha secretion (P < 0.05) by both groups of PBMCs. Our results show for the first time that the RA patients have an increased humoral response to human Hsp40 proteins Hdj2 and Hdj3. This is also the first description of immunomodulatory effect of human Hsp40s on T cells and cytokine secretion in RA, suggesting that Hsp40s act as natural anti-inflammatory agents in RA.