Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
16362817 LST1 and NCR3 expression in autoimmune inflammation and in response to IFN-gamma, LPS and 2006 Jan Many genes in the central region of the major histocompatibility complex (MHC) encode proteins involved in immune and inflammatory responses. In this study, we have further characterized two genes in the MHC class IV region, leucocyte-specific transcript (LST) 1 and natural cytotoxicity-triggering receptor 3 (NCR3) (also known as 1C7 and natural killer (NK)p30). The specific function of LST1 is not known, although expression analysis and functional data suggest an immunomodulatory role. The LST1 gene undergoes extensive alternative splicing, giving rise to both membrane-bound (encoded by exon 3) and soluble isoforms. The NCR3 protein is involved in NK-mediated cytotoxicity and plays a role in NK/dendritic cell crosstalk. Expression of these genes was examined, by real-time reverse transcriptase-polymerase chain reaction, in autoimmune-induced inflammation, specifically rheumatoid-arthritis-affected blood and synovium, and in response to stimulation with inflammatory mediators and bacterial agents. The expression of LST1, specifically splice variants encoding soluble isoforms and NCR3, was increased in rheumatoid-arthritis-affected blood and synovium and was associated with more severe inflammation in the synovium. Furthermore, both genes were significantly up-regulated in response to lipopolysaccharide, interferon (IFN)-gamma and bacterial infection. These findings suggest that NCR3 and soluble isoforms of LST1 may play a role in inflammatory and infectious diseases.
15940561 Serum cartilage oligomeric matrix protein (COMP) in rheumatoid arthritis and knee osteoart 2005 Jun The cartilage oligometrix matrix protein (COMP) is a noncollagenous protein, a glycoprotein, the function of which is to bind to type II collagen fibres and stabilise the collagen fibre network in the articular cartilage. In the serum of the normal population the COMP level is 5 mug/ml. An increased level of COMP in the synovial fluid was described in the early stage of rheumatoid arthritis (RA), whereas in advanced stages of RA, the level of COMP decreased. In this study we assessed the serum COMP level in patients with RA and knee osteoarthritis (OA) and found a correlation between the serum COMP level and other markers as well as bone mass density (BMD) changes, activity of disease, disease duration and the age of the patients. The blood was collected from 30 RA patients and 30 OA patients who constituted the control group. The serum COMP level was determined using an inhibition enzyme-linked immunosorbent assay (ELISA). The average value of the serum COMP level in RA patients was 10.4+/-3.6 U/l. There was a correlation between the serum COMP level and the age of RA patients (p<0.005) and disease activity score (DAS) value (p<0.01). According to correlation coefficients, the serum COMP level was independent of stage of disease, number of painful and swollen joints, duration of morning stiffness, disease duration and titre of the Waaler-Rose test. The influence of rheumatoid nodule presence on the serum COMP level was shown (p<0.05). In RA patients with erythrocyte sedimentation rate (ESR) values below 20 mm/h compared with patients with ESR values over 60 mm/h, the serum COMP level was observed to be significantly lower (p<0.05). The average value of COMP in OA patients was 10.4+/-2.7 U/l. No correlation was found between the serum COMP level and patients' age and disease duration. There was a correlation between the serum COMP level and Western Ontario and McMaster Universities (WOMAC) index pain scale for the lower limbs (p<0.005) and T-score value of densitometry examinations (p<0.036) in OA patients. No statistical differences were found between the average serum COMP level in RA and OA patients.
16173243 Magnetic resonance imaging findings of the cervical spine in patients with rheumatoid arth 2005 Sep OBJECTIVES: To investigate by magnetic resonance (MR) imaging the occurrence of cervical spine (CS) involvement in rheumatoid arthritis (RA) patients. METHODS: Fifty-one consecutive unselected patients, who fulfilled the revised American College of Rheumatology criteria for RA, were investigated. All patients had a complete physical and laboratory evaluation. Radiological evaluation included hand and wrist x-rays, as well as CS radiographs in anteroposterior, lateral and lateral in full flexion views. In addition, MR (Spin Echo T2-weighted sagittal scans [neutral and flexion position], plain and contrast enhanced T1-weighted sagittal and axial scans) was performed in all patients. Hand x-rays were evaluated according to the Larsen's criteria, while CS radiographs were evaluated according to Winfield classification. Disease activity was assessed by disease activity score for 28 joint indices (DAS-28). RESULTS: There were 42 females and 9 males with a mean age of 56.5 +/- 10.4 years and mean disease duration 12.4 +/- 8.5 years. Thirty-three patients (64.7%) had positive IgM rheumatoid factor (RF). Thirty patients presented clinical findings, mainly cervical pain and stiffness of CS (25 with positive and 5 with negative MR), while, radiological findings of CS involvement were found in 40 patients. Forty-four patients (86.2%) presented MR findings of CS involvement (peridental pannus 88%; dens erosion 23.5%; atlantoaxial subluxation 13.7%; subaxial subluxations 10%; brainstem compression 5.9%). Peridental pannus correlated with high DAS-28, positive IgM RF and advanced erosive changes of the wrist and hand (p < 0.05) in the univariate analysis. However, multivariate logistic regression analysis did not confirm such correlation. CONCLUSIONS: We conclude that the frequency of CS involvement in Greek RA patients is high but the destructive changes are mild. However, in patients with active erosive peripheral disease it is very probable to also have some changes in CS. These may be clinically important and in such cases, MR may offer valuable information.
16206283 Visualization and in situ analysis of leukocyte trafficking into the ankle joint in a syst 2005 Oct OBJECTIVE: To describe the kinetics of leukocyte migration into a distal joint during the development of chronic inflammation in a murine model of rheumatoid arthritis (RA), to identify leukocyte subpopulations recruited in the synovial vessels, and to test in real time the effects of an antiinflammatory compound on leukocyte-endothelial cell interactions in the arthritic joint. METHODS: We used intravital video microscopy (IVM), which was adapted to the microcirculation of the mouse ankle, to monitor the kinetics of leukocyte-endothelium interactions (rolling and firm adhesion) during the onset and progression of proteoglycan-induced arthritis (PGIA), a chronic autoimmune model of RA. Subpopulations of rolling and adherent leukocytes were identified by in vivo immunostaining. Leukocyte extravasation into the ankle joint was verified histologically. RESULTS: Between the onset of arthritis and the beginning of the destructive phase of PGIA, we found a steady increase in the number of leukocytes that exhibited firm adherence to the endothelium of synovial vessels, which clearly underscores the chronic, self-perpetuating character of joint inflammation in this autoimmune model. We showed, however, that granulocytes, and not T cells, constituted the major cell population that was continuously recruited to the inflamed ankle. Using IVM, we could detect instant changes in leukocyte adhesion behavior in the synovial vessels of the arthritic joint upon administration of a compound that antagonizes leukocyte rolling. CONCLUSION: IVM of the microcirculation of the mouse ankle could become an essential tool for investigating the mechanisms that regulate leukocyte migration to the joint in systemic models of RA as well as for preclinical testing of antiinflammatory therapies.
16541480 Effects of infliximab treatment on lipoprotein profile in patients with rheumatoid arthrit 2006 May OBJECTIVE: To investigate the longterm effects of the anti-tumor necrosis factor (TNF) therapy infliximab, a drug known to reduce disease activity in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS). METHODS: Eighty-two patients (50 with RA, 32 with AS) aged 17-77 years were enrolled. All patients were treated with intravenous infliximab. Lipid profile was assessed at baseline and after 6 months of treatment. RESULTS: Disease activity significantly decreased in patients with RA and AS at the end of infliximab therapy. Infliximab treatment significantly increased total cholesterol from 206 to 216 mg/dl (p < 0.05) and triglycerides from 109 to 122 mg/dl (p < 0.05). The low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol did not change during treatment. Furthermore, the total cholesterol/HDL cholesterol and triglycerides/HDL cholesterol ratios did not change significantly. CONCLUSION: The influence of infliximab treatment on lipid profile seems to be neutral, since neither LDL cholesterol levels nor total cholesterol/HDL cholesterol and triglycerides/HDL cholesterol ratios changed significantly during the 6-month therapy. Our findings suggest that the favorable effect of infliximab treatment on cardiovascular comorbidity may not be mainly mediated by the effects on the lipid profile, but further investigations are needed in order to confirm this hypothesis.
15954510 Statin therapy in rheumatoid arthritis. 2005 May Rheumatoid arthritis, a chronic inflammatory polyarthritis that destroys synovial joints, is associated with systemic as well as local inflammation and with an increased risk of cardiovascular disease and death not fully explained by traditional cardiac risk factors. Statins (HMG-coA reductase inhibitors), medications originally designed to lower cholesterol, have been shown to have powerful effects on decreasing cardiovascular mortality rates in the general and high-risk populations. Not all of this protective benefit appears to be mediated by lowered cholesterol levels. Statins also influence multiple steps in the inflammatory process, including leukocyte migration and adhesion, T-cell stimulation, nitric oxide bioavailability, generation of free radicals, and angiogenesis. Recent studies show that statins may provide mild anti-inflammatory benefit in rheumatoid arthritis, in addition to reducing cardiovascular risk.
16214092 Emerging biologic drugs for the treatment of rheumatoid arthritis. 2005 Nov This article reviews the role of emerging biologic drugs for the treatment of rheumatoid arthritis (RA). Besides anti-tumor necrosis factor (TNF)-alpha and anti-interleukin (IL)-1 agents (Infliximab, Adalimumab, Etanercept and Anakinra) whose clinical efficacy is now established, new drugs have been proposed for the therapy of rheumatoid arthritis patients not responding to conventional treatments. These approaches include the blockade of B-cell activity with anti-CD20 monoclonal antibody (Rituximab) and the inhibition of T-cell activation with fusion protein CTLA4Ig. Moreover, promising results have been obtained in animal models utilizing suppressors of cytokine signaling (SOCS) and dominant-negative TNF variants to inactivate TNF signaling.
16252188 Scintigraphic diagnosis of protein-losing enteropathy secondary to amyloidosis. 2005 Mar Protein-losing enteropathy is an uncommon syndrome of excessive loss of protein via the gastrointestinal mucosa. 99mTc-dextran scintigraphy was performed on a 42-year-old woman with protein-losing enteropathy. She had secondary amyloidosis due to rheumatoid arthritis. Abnormal leakage of the radiotracer was observed in the mid-abdominal region suggesting the site of protein loss. It is concluded that 99mTc-dextran scintigraphy is useful as a noninvasive and simple test for the imaging and confirmation of diagnosis in protein-losing enteropathy.
15930708 [Secondary osteoporosis and bone quality]. 2005 Jun In secondary osteoporosis, rheumatoid arthritis patients showed high bone turnover and the same cut-off value in bone mineral density as postmenopausal osteoporosis. On the other hand, Glucocorticoid-induced osteoporosis showed low bone turnover and the higher cut-off value compared with postmenopausal osteoporosis. Examination about secondary osteoporosis except these conditions is needed.
16078347 Use of combination of leflunomide with biological agents in treatment of rheumatoid arthri 2005 Aug An Expert Panel Meeting was held in May 2004 to assess experience with combination therapy with leflunomide and biological agents in the treatment of rheumatoid arthritis (RA), to identify both optimal use of such combinations and precautions for use. Eleven published prospective or retrospective studies were reviewed, principally evaluating combination of leflunomide with infliximab, as well as patient registry data. Available data suggest that combination therapies are more efficacious than monotherapies, reflecting the complementarity of mechanisms of action. Information on side effects remains contradictory, and tolerability of these combinations may vary between different patient groups. In some studies, tolerability is equivalent to that seen with monotherapy; in others a high rate of adverse events has led to frequent treatment discontinuation. Dermatological reactions may be a specific side effect of these combination therapies. Combination therapy is considered justified for treatment of patients diagnosed early who are at risk for rapid progression and for patients who fail to respond to monotherapy. The majority of participants favored adding biological agents to a previously established leflunomide monotherapy rather than starting both treatments simultaneously. On the other hand, combination therapy should be considered with caution in patients with a history of treatment failure, with hepatic comorbidity, or with other autoimmune disease, and in immunocompromised patients. When considering initiation of combination therapy, it is important to provide full information to the patient on the potential benefits and risks of such treatment and to integrate patients as far as possible into the decision-making process.
16929448 Patients with and without rheumatoid arthritis benefit equally from preoperative epoetin-a 2006 Aug BACKGROUND: Preoperative epoetin-alpha administration is said to have a limited effect in patients with chronic inflammatory diseases such as rheumatoid arthritis (RA), due to lower iron availability. We studied the effects of preoperative epoetin-alpha treatment in orthopedic surgery patients in a daily life setting in which iron supplementation was assured, and compared the effects in RA and non-RA patients. METHODS: In an open, naturalistic, randomized controlled trial, 695 orthopedic surgery patients with preoperative hemoglobin (Hb) values of 10-13 g/dL, either with RA (113) or without RA (582), received either preoperative epoetin-alpha treatment added to standard care, or standard care alone. Hb values and transfusions were evaluated from entry into the study until 4-6 weeks after surgery. RESULTS: Both in RA and non-RA patients, perioperative Hb values were significantly higher and transfusion requirements were significantly lower in epoetin-alpha treated patients than in control patients (p < 0.001). In RA patients, the outcomes regarding Hb values were not significantly or relevantly different from non-RA patients. INTERPRETATION: Just as with orthopedic patients in general, RA patients benefit from preoperative epoetin-alpha treatment in combination with iron supplementation. We postulate that iron supplementation during epoetin-alpha therapy in RA patients is important for optimal efficacy.
17095372 An analysis of women's and men's surgical priorities and willingness to have rheumatoid ha 2006 Nov PURPOSE: Our prior national study showed gender differences in the rates of rheumatoid arthritis hand surgery. This project evaluated whether men's versus women's preferences, as opposed to physician biases, contribute to these variations. METHODS: A self-administered questionnaire was administered to 126 patients with rheumatoid arthritis at our institution; 117 (93%) of these patients completed the questionnaire. Chi-square tests, t tests, the Wilcoxon rank sum test, and multiple logistic regressions were used for the analyses. The results were compared with our national mailed survey of 500 rhematologists and 500 hand surgeons in the United States that evaluated physicians' attitudes toward the indications and outcomes of rheumatoid hand surgery. RESULTS: When we asked physicians who values hand aesthetics more, 378 (73%) chose women compared with less than 2 (1%) who chose men; when asked who values hand function more, 35 (7%) chose women, 83 (16%) chose men, and 396 (77%) thought there was no difference; and when asked who is more willing to have hand surgery, 219 (43%) chose women compared with 6% who chose men. In this patient survey, however, women and men were equally willing to have hand surgery, and they placed equal value in hand appearance, function, and pain. Women, however, appeared more risk adverse and concerned about the potential pain and inconvenience from surgery. CONCLUSIONS: Physicians' biases appear to conflict with patient preferences regarding rheumatoid hand surgery. Physicians should understand patients' preferences during the shared decision-making process for surgery.
16120072 Leflunomide in the treatment of rheumatoid arthritis. An analysis of predictors for treatm 2005 Sep AIMS: To determine factors predictive for leflunomide drug survival in an outpatient population with rheumatoid arthritis in a setting of care-as-usual. METHODS: A standard dataset was collected from medical records of consecutive outpatients on leflunomide treatment for rheumatoid arthritis between January 2000 and June 2003. The dataset consisted of patient, disease and treatment characteristics at the start of leflunomide treatment, and data on leflunomide use. RESULTS: Leflunomide was started in 279 patients and 173 patients (62.0%) withdrew from treatment during follow-up. From univariate analysis, concomitant systemic corticosteroid use [hazard ratio (HR) (95% confidence interval) 1.35 (1.00, 1.83)] and an erythrocyte sedimentation rate <35 mm h(-1)[HR 1.38 (1.01, 1.88)] at start of leflunomide were found to be predictive for better leflunomide survival. Furthermore, the attending rheumatologist was correlated with leflunomide drug survival. Hazard ratios varied, depending on the individual rheumatologist, from 0.60 to 2.66. Multivariate analysis suggested attending rheumatologist (HR varying from 0.54 to 2.30 depending on the individual rheumatologist), concomitant systemic corticosteroid use [HR 1.58 (1.14 2.21)] and erythrocyte sedimentation rate <35 mm h(-1)[HR 1.42 (1.03, 1.96)] at start of leflunomide to be associated with leflunomide survival. CONCLUSIONS: Concomitant systemic corticosteroid use, erythrocyte sedimentation rate at the start of treatment and attending rheumatologist were found to be predictive for leflunomide survival. Information on these predictors at the start of leflunomide therapy may offer information on which patients are at an increased risk of withdrawal from leflunomide. Whether this information leads to optimization of leflunomide treatment outcomes remains to be studied.
16965199 Comorbidity of fibromyalgia and psychiatric disorders. 2006 Aug OBJECTIVE: To assess the co-occurrence of fibromyalgia with psychiatric disorders in participants of a fibromyalgia family study. METHOD: Patients (probands) with fibromyalgia, control probands with rheumatoid arthritis, and first-degree relatives of both groups completed a structured clinical interview and tender point examination. The co-occurrence odds ratio (OR) (the odds of a lifetime comorbid DSM-IV disorder in an individual with fibromyalgia divided by the odds of a lifetime comorbid disorder in an individual without fibromyalgia, adjusted for age and sex) was calculated; observations were weighted by the inverse probability of selection, based on the fibromyalgia status of the pro-band; and standard errors were adjusted for the correlation of observations within families. The study was conducted from September 1999 to April 2002. RESULTS: We evaluated 78 fibromyalgia pro-bands and 146 of their relatives, and 40 rheumatoid arthritis probands and 72 of their relatives. Among the relatives of both proband groups, we identified 30 cases of fibromyalgia, bringing the total number of individuals with fibromyalgia to 108, compared with 228 without fibromyalgia. The co-occurrence ORs for specific disorders in individuals with versus those without fibromyalgia were as follows: bipolar disorder: 153 (95% CI = 26 to 902, p < .001); major depressive disorder: 2.7 (95% CI = 1.2 to 6.0, p = .013); any anxiety disorder: 6.7 (95% CI = 2.3 to 20, p < .001); any eating disorder: 2.4 (95% CI = 0.36 to 17, p = .36); and any substance use disorder: 3.3 (95% CI = 1.1 to 10, p = .040). CONCLUSIONS: There is substantial lifetime psychiatric comorbidity in individuals with fibromyalgia. These results have important clinical and theoretical implications, including the possibility that fibromyalgia might share underlying pathophysiologic links with some psychiatric disorders.
15843240 Soluble transferrin receptor and transferrin receptor-ferritin index in iron deficiency an 2005 The aim of the study was to evaluate the clinical efficiency of soluble transferrin receptor and transferrin receptor-ferritin index (sTfR/logF) in the diagnosis of iron deficiency anemia, as well as the differential diagnosis of iron deficiency anemia and anemia in rheumatoid arthritis. The study included 96 patients with anemia and 61 healthy volunteers as a control group. In healthy subjects there were no significant sex and age differences in the parameters tested. The study results showed these parameters to be reliable in the diagnosis of iron deficiency anemia, as well as in the differential diagnosis of iron deficiency anemia and anemia of chronic disease. The results indicate that sTfR/logF could be used to help differentiate coexisting iron deficiency in patients with anemia of chronic disease. Receiver operating characteristic analysis showed a higher discriminating power of transferrin receptor-ferritin index vs. soluble transferrin receptor in the diagnosis of iron deficiency anemia, as well as in the differential diagnosis between iron deficiency anemia and anemia of chronic disease. In patients with anemia in rheumatoid arthritis, the parameters tested showed no significant differences with respect to C-reactive protein concentration. These results suggested that the parameters tested are not affected by acute or chronic inflammatory disease.
16095007 Anti-nucleosome antibodies in the diagnosis of systemic lupus erythematosus. 2005 Mar OBJECTIVE: To study the prevalence and diagnostic significance of antibodies against nucleosomes in patients with systemic lupus erythematosus (SLE) as compared to five anti-nuclear antibody (ANA) assays. METHODS: The study included 305 patients with SLE, 125 patients with other autoimmune rheumatic diseases, and 415 healthy controls. Anti-nucleosome antibodies were measured by an enzyme-linked immunosorbent assay (ELISA) and ANA by immunofluorescence (IF) using Hep-2 cells. Anti-double-stranded DNA (anti-dsDNA) antibodies were measured by three commercial ELISAs and by IF using Crithidia luciliae as antigen. RESULTS: Compared to three ELISAs for anti-dsDNA, the anti-nucleosome assay was less sensitive (30% vs. 29-69%) but equally specific (90% vs. 77-95%) for SLE. The most sensitive test was ANA (76%), and the least sensitive was Crithidia (13%). The correlations between the different assays were good (p < 0.001 for all comparisons). CONCLUSION: The anti-nucleosome antibody assay does not offer additional information compared to conventionally used anti-dsDNA tests in the differential diagnosis of SLE.
15742153 Fc receptors and their role in immune regulation and autoimmunity. 2005 Jan The activation threshold of cells in the immune system is often tuned by cell surface molecules. The Fc receptors expressed on various hematopoietic cells constitute critical elements for activating or downmodulating immune responses and combines humoral and cell-mediated immunity. Thus, Fc receptors are the intelligent sensors of the immune status in the individual. However, impaired regulation by Fc receptors will lead to unresponsiveness or hyperreactivity to foreign as well as self-antigens. Murine models for autoimmune disease indicate the indispensable roles of the inhibitory Fc receptor in the suppression of such disorders, whereas activating-type FcRs are crucial for the onset and exacerbation of the disease. The development of many autoimmune diseases in humans may be caused by impairment of the human Fc receptor regulatory system. This review is aimed at providing a current overview of the mechanism of Fc receptor-based immune regulation and the possible scenario of how autoimmune disease might result from their dysfunction.
17343251 Lack of agreement between patients' and physicians' perspectives of rheumatoid arthritis d 2006 Nov OBJECTIVE: To obtain information on changes in patients' satisfaction (PATSAT) and physicians' global assessment (PhGASS) with regard to rheumatoid arthritis (RA) activity fluctuations. METHODS: Eighty-eight RA outpatients out of 207 investigated were assessed for 3 months on average after the initial evaluation. PATSAT (1 = excellent to 5 = unsatisfactory), PhGASS (visual analogue scale 1-100), and the 28-joint Disease Activity Score (DAS28) were assessed as at the first evaluation. The only prerequisite for enrolment was any therapeutic change at the first visit. Changes in PATSAT (SATCH) and PhGASS (PhGACH) were categorized and subsequently related to the DAS28 changes. Statistical evaluation was carried out by the Kruskal-Wallis test, the Mann-Whitney U-test, and by kappa statistics. RESULTS: To achieve a positive SATCH (n = 26/88 patients), a median DAS28 reduction of -1.06 (-25.0%) was necessary, whereas a considerably lower median increase of +0.16 (+10.5%) caused a negative SATCH. PhGASS (n = 38/88 patients) changed positively on a median DAS28 reduction of -0.82 (-16.0%), whereas it worsened at a mean DAS28 increase of +0.55 (+16.5%). Approximately 60% congruence between SATCH and PhGACH could be observed (kappa = 0.139). The DAS28 values preceding a positive SATCH and PhGACH were significantly higher (p < 0.001) than before a negative change. CONCLUSION: The patients' perspective with respect to improvement or worsening of RA is asymmetric. In contrast to the physicians' perspective, patients require greater improvement to be satisfied and less deterioration to be dissatisfied. These results may provide additional guidance in considerations about defining response and non-response in RA.
17207379 Interleukin-1 receptor antagonist (IL-1RN) and interleukin-1B gene polymorphisms in Turkis 2006 Nov OBJECTIVE: Interleukin 1 (IL-1) family is composed of two agonists, IL-1alpha and IL-1Beta and IL-1 receptor antagonist, IL-1Ra. The purpose of this study was to determine the relationship between polymorphisms of IL-1 receptor antagonist (IL-1RN), IL-1B promoter and IL-1B exon 5 genes and susceptibility to rheumatoid arthritis (RA) in Turkish population. METHODS: Polymerase chain reaction (PCR) was used to determine the genotype of the IL-1RN for 94 RA patients and 104 healthy controls. Genotyping of IL-1B polymorphisms at positions -511 (C/T) and +3953 (C/T) was detected by PCR followed restriction fragment length analysis. RESULTS: There was no significant difference in IL-1RN genotype and allele distributions between RA and the control groups. In addition, no significant association was observed in the allelic frequency (C or T) of IL-1B promoter (-511) between RA patients and the controls (P = 0,118), but the genotype distribution of 1/2 (C/T) at position -511 showed a significant difference (P = 0,038). Also, 2/2 genotype (T/T); (P = 0,028), and allele 2 (T) distribution (P = 0,011) of IL-1B (+3953) showed significant differences between RA patients and the control groups in the study population. CONCLUSION: These results imply that 2/2 (T/T) genotype or allele 2 (T) of IL-B (+3953) are susceptibility factors for RA in Turkey. Also, 1/2 genotype (C/T) of IL-1 -511 can play a protective role for RA.
15829573 Outcome of intensive immunosuppression and autologous stem cell transplantation in patient 2005 Oct OBJECTIVE: To determine clinical and immunological correlates of high dose chemotherapy (HDC) + autologous stem cell transplantation (ASCT) in patients with severe rheumatoid arthritis (RA), refractory to conventional treatment. METHODS: Serial samples of peripheral blood and synovial tissue were obtained from seven patients with RA treated with HDC and autologous peripheral blood grafts enriched for CD34+ cells. Disease activity was assessed with the Disease Activity Score (DAS), serum concentrations of C reactive protein (CRP), and human immunoglobulin (HIg) scans, and the extent of immunoablation was determined by immunophenotyping of peripheral blood mononuclear cells, and immunohistochemistry and double immunofluorescence of synovium. RESULTS: Clinical responders (n = 5) had a larger number of cells at baseline expressing CD3, CD4, CD27, CD45RA, CD45RB, and CD45RO in synovium (p < 0.05), higher activity on HIg scans (p = 0.08), and a trend towards higher concentrations of CRP in serum than non-responders (n = 2). Subsequent remissions and relapses in responders paralleled reduction and re-expression, respectively, of T cell markers. A relatively increased expression of CD45RB and CD45RO on synovial CD3+ T cells was seen after HDC + ASCT. No correlations were found between DAS and changes in B cells or macrophage infiltration or synoviocytes. CONCLUSIONS: HDC + ASCT results in profound but incomplete immunoablation of both the memory and naïve T cell compartment, which is associated with longlasting clinical responses in most patients. The findings provide strong circumstantial evidence for a role of T cells in established RA, and demonstrate a role for the synovium in post-transplantation T cell reconstitution.