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ID PMID Title PublicationDate abstract
18619538 Immunogenicity of anti-tumor necrosis factor antibodies-toward improved methods of anti-an 2008 Aug To date, millions of people have been treated with therapeutic monoclonal antibodies (TmAbs) for various indications. It is becoming increasingly clear that TmAbs can be immunogenic, which may reduce efficacy or induce adverse effects. Over the years, the importance of antibody formation has been questioned and sometimes minimized, as few antibody responses to TmAbs (HACA or HAHA) were reported. However, the methods to detect and quantify such antibodies used in the past have been problematic. Only recently, methods have been developed that have adequate sensitivity and are not seriously disturbed by false-positive reactions caused by rheumatoid factors, natural antibodies to Fab or F(ab')2 fragments, or Fc interactions of IgG4. The large number of treated patients, in combination with these new assays, presents a unique opportunity to study the anti-antibody immune response in man, possibly allowing us to manipulate immunogenicity in the future.
16460255 Periodontal and hematological characteristics associated with aggressive periodontitis, ju 2006 Feb BACKGROUND: Periodontitis shares several clinical and pathogenic characteristics with chronic arthritis, and there is some degree of coexistence. The aims of this study were to elucidate whether patients with localized aggressive periodontitis (LAgP), generalized aggressive periodontitis (GAgP), juvenile idiopathic arthritis (JIA), and rheumatoid arthritis (RA) share periodontal and hematological characteristics distinguishing them from individuals free of diseases. METHODS: The study population consisted of white adults (or=4 mm, CAL>or=2 mm, and ABL>or=2 mm compared to controls. The percentage of sites with CAL>or=2 mm significantly correlated with the levels of IgM-RF and IgA-RF. Missing teeth in JIA and RA patients were not lost due to periodontitis. Patients with GAgP showed higher levels of leukocytes, including neutrophils, and CRP compared to controls. In part, JIA and RA patients showed similar results. CONCLUSIONS: Young adults with RA may develop periodontal destruction, and these patients require professional attention. Both differences and similarities in periodontal and hematological variables were seen in individuals with periodontitis, JIA, and RA.
18821697 Antagonism of the human epidermal growth factor receptor family controls disease severity 2008 Oct OBJECTIVE: To evaluate the therapeutic potential of the human epidermal growth factor receptor (HER) family inhibitor, herstatin, in an animal model of arthritis. METHODS: Constructs of herstatin and modified tissue plasminogen activator (tPA)-herstatin were expressed in HEK 293T cells, and secreted protein was analyzed by Western blotting. Tissue PA-herstatin adenovirus (Ad-tPA-Her) was prepared, and titers established. Gene expression of Ad-tPA-Her was determined by polymerase chain reaction using HeLa cells. Pharmacokinetics of gene and protein expression in vivo in liver tissue and serum samples were confirmed via intravenous administration of Ad-tPA-Her. Clinical signs of disease were monitored in arthritic DBA/1 mice after therapeutic administration of Ad-tPA-Her, and histologic analysis of hind foot specimens was performed. RESULTS: Native herstatin was not secreted in supernatants, while modified tPA-herstatin was detected in abundance. HeLa cells stably expressed the tPA-herstatin gene when infected with virus. Additionally, tPA-herstatin gene and protein expression was observed over time in mice treated with virus. Importantly, Ad-tPA-Her, when administered therapeutically to arthritic mice, controlled clinical and histologic signs of disease and reduced the number of joints with severe damage. CONCLUSION: Our results support the notion that the human epidermal growth factor receptor family has a role in the progression of collagen-induced arthritis. The novel tPA-herstatin fusion protein could be used as an effective therapeutic tool for control of inflammatory disorders involving an angiogenic component.
18817899 Cardiovascular involvement in systemic autoimmune diseases. 2009 Feb Autoimmune diseases, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), primary antiphospholipid syndrome (APS), systemic sclerosis and systemic vasculitis, affect a large number of people in whom one of the leading causes of morbidity and mortality is cardiovascular disease. Cardiovascular disease is associated with the development of accelerated atherosclerosis. It seems to occur at a younger age than in the general population, is often asymptomatic and, in addition to traditional risk factors, also involves specific risk factors as chronic inflammation, the duration and activity of the autoimmune disease, and immunosuppressive therapy. The early phases of cardiovascular involvement in patients with autoimmune diseases may be clinically silent, with only a microcirculation disorder present. There are various means of detecting morphological cardiac damage: coronary angiography remains the gold standard for diagnosing coronary stenosis, but new, non invasive and more reliable methods have been introduced into clinical practice in order to detect subclinical microcirculation abnormalities.
18391903 Cemented primary total arthroplasty for acetabular protrusion in patients with rheumatoid 2008 Jan BACKGROUND: The degenerative changes in hip joints observed in patients RA are associated with acetabular bone deficiencies. Therefore total hip arthroplasty performed in such patients requires bone grafting to restore the deficiencies. The aim of the study was to assess the long term-term results of primary total hip arthroplasty in patients with RA including an assessment of the usefulness of auto-and allograft in restoring bone deficiencies in acetabular protrusion. MATERIAL AND METHODS: From 1991 to 2001 a total of 156?? [w tekście jest mowa o 158] patients with rheumatoid arthritis of the hip joint underwent a primary total arthroplasty of the hip joint with acetabular protrusion. The reconstruction of the acetabular bone was achieved by morsellized impaction auto-and allografting. Group I included 26 patients who received autografts and Group II consisted of 10 patients who received allografts. The mean follow-up was 5 years. The hip joint performance was assessed according to the following scales: WOMAC, HHS, and Merle-d'Aubigne-Postel. Graft incorporation was graded according to the Avci criteria. RESULTS: The study revealed that auto-and allografting provides good long-term results. Graft incorporation was reported after 26 months. The radiographs showed porotic bone in grafts in one of the patients; however, there were no signs of loosening in the prosthetic acetabulum. CONCLUSION: Restoration of bone deficiencies in the medial part of the acetabulum in patients with RA by bone grafting is a biological way of reconstruction of the bone and facilitates stable fixation of a polyethylene acetabulum.
17907188 Central role of the MEK/ERK MAP kinase pathway in a mouse model of rheumatoid arthritis: p 2007 Oct OBJECTIVE: To evaluate the role of the MEK/ERK MAP kinase pathway in murine collagen-induced arthritis (CIA) using the selective MEK inhibitor PD184352. We examined the effects of the inhibitor in cytokine-stimulated synovial fibroblasts and in cytokine-induced arthritis in rabbits to investigate its antiinflammatory mechanisms. METHODS: Murine CIA was used to assess the effects of the selective MEK inhibitor on paw edema, clinical scores, weight loss, histopathologic features, and joint levels of p-ERK. Western blotting and immunohistochemistry techniques were used to assess p-ERK in human and rabbit synovial fibroblasts and synovial tissue from rheumatoid arthritis (RA) patients. Interleukin-1alpha (IL-1alpha)-stimulated stromelysin production in rabbit synovial fibroblasts was assessed by enzyme-linked immunosorbent assay. A rabbit IL-1alpha-induced arthritis model was used to assess the effects of the inhibitor on IL-1alpha-induced MEK activity, stromelysin production, and cartilage degradation. RESULTS: In the CIA model, PD184352 inhibited paw edema and clinical arthritis scores in a dose-dependent manner. Disease-induced weight loss and histopathologic changes were also significantly improved by treatment. Inhibition of disease-induced p-ERK levels in the joints was seen with the inhibitor. Levels of p-ERK in the synovium were higher in RA patients than in normal individuals. PD184352 reduced IL-1alpha-induced p-ERK levels in human RA synovial fibroblasts. The production of p-ERK and stromelysin was also inhibited in IL-1alpha-stimulated rabbit synovial fibroblasts. We observed IL-1alpha-induced p-ERK in the synovial lining, subsynovial vasculature, and articular chondrocytes. IL-1alpha-induced stromelysin production and proteoglycan loss from the articular cartilage were reduced by PD184352. CONCLUSION: These data demonstrate the inhibition of murine CIA by PD184352, support the hypothesis that antiinflammatory activity contributes to the mechanism of action of the inhibitor, and suggest that a selective inhibitor may effectively treat RA and other inflammatory disorders.
17043048 The differential expression of corticosteroid receptor isoforms in corticosteroid-resistan 2007 Apr OBJECTIVE: A proportion of patients with rheumatoid arthritis (RA) fail to respond adequately to corticosteroid (CS) therapy. Using an in vitro CS sensitivity bioassay, we have subdivided RA patients into steroid-sensitive (SS) and -resistant (SR) subgroups and this correlates with clinical responses to CS therapy. CSs exert their effects via the CS receptor (CR), which exists as two main isoforms, CRalpha and CRbeta. CRbeta can function as a negative inhibitor of CRalpha. We have hypothesized that steroid resistance in RA patients is due in part to a relative over-expression of the CRbeta. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from SS and SR RA patients. CRalpha and CRbeta mRNA expression was determined by quantitative real time polymerase chain reaction (qRT-PCR). The ratio of CRbeta/CRalpha mRNA expression was determined. CRalpha and CRbeta protein expression by PBMCs was analysed by flow cytometry. RESULTS: qRT-PCR analysis showed a trend towards higher expression of both CRbeta and basal CRbeta/CRalpha ratio in SR RA patients. Stimulation of PBMCs in vitro with concanavalin-A induced a significantly higher CRbeta mRNA expression, and CRbeta/CRalpha ratio in SR RA patients compared with SS patients, which was not inhibited by hydrocortisone. Flow cytometry showed that the percentage of PBMCs staining for CRbeta protein was significantly lower in the SS RA group (SS 43.3 +/- 14.8% vs SR 88.6 +/- 8.6%; P < 0.0010). The mean intensity of fluorescence CRbeta staining was higher in the SR RA patients (P < 0.001). CONCLUSION: We show for the first time that CRbeta is over-expressed in SR RA patients and that hydrocortisone fails to inhibit concanavalin-A stimulated increase in CRbeta mRNA in SR RA patients. This mechanism may contribute in part to the CS hyporesponsiveness seen in some RA patients.
16362448 Clinical significance of IL-18, IL-15, IL-12 and TNF-alpha measurement in rheumatoid arthr 2006 Jul The aim of the study was to evaluate the clinical significance of serum (S) and synovial fluid (SF) interleukin (IL)-18, IL-15, IL-12 and the tumor necrosis factor alpha (TNF-alpha) measurements in relation to laboratory and clinical measures of disease activity of patients with active rheumatoid arthritis (RA). Sixty-four patients with RA and 25 patients with osteoarthritis (OA) were included in this study. RA activity was determined using the Disease Activity Score (DAS) 28 index. Concentrations of IL-18, IL-15, IL-12 and TNF-alpha were measured by ELISA. Serum C-reactive protein (CRP) levels were also determined. Cross-sectional correlations between S and SF levels of cytokines and values of DAS 28 index were calculated. The results have shown that IL-18, IL-15, IL-12 and TNF-alpha levels in S and SF of patients with RA were significantly higher than the levels obtain from patients with OA (p<0.01). Significantly higher levels of IL-18, IL-15 and TNF-alpha were found in the SF compared to the S of patients with RA (p<0.01). Significantly higher S and SF levels of all four cytokines and serum CRP values were found in RA patients with high disease activity (DAS 28>5.1) compared to those with mild (DAS 28>3.2) and low disease activity (DAS 28>2.6) (p<0.01). Serum and SF concentrations of all four cytokines positively correlated with DAS 28 index values, i.e., disease activity. A poor correlation was found for S and SF IL-12 whereas the highest coefficient of correlation was found for SF IL-18 (r=0.879, p<0.01), and SF TNF-alpha (r=0.827, p<0.01) and disease activity in this study. Strong correlation was found between SF TNF-alpha and SF IL-18 levels (r=0.732, p<0.01). In conclusion, SF IL-18 and TNF-alpha levels in RA patients are good indicators of disease activity. The results obtained support the use of the DAS in clinical practice as a reliable method in assessing disease activity in RA patients.
18237470 Suppression of adjuvant arthritis by hesperidin in rats and its mechanisms. 2008 Feb The citrus flavonoid hesperidin has been reported to possess a wide range of pharmacological properties. We have investigated the preventive and therapeutic effects of hesperidin on the development of adjuvant arthritis (AA), a rat model of rheumatoid arthritis (RA). Freund's complete adjuvant was used to induce AA in rats. Secondary paw swelling, polyarthritis index and histopathological assessment of ankle joints were used to evaluate the effects of hesperidin on AA rats. Concanavalin-A-induced T-lymphocyte proliferation and interleukin (IL)-2 production by splenocytes were measured using the MTT assay. Levels of IL-1, IL-6 and tumour necrosis factor (TNF)-alpha secreted by peritoneal macrophages (PM) were measured by RIA. Intragastric administration of hesperidin significantly attenuated secondary paw swelling and reduced the polyarthritis index of AA rats in a dose-dependent manner. In addition, hesperidin clearly ameliorated the pathological changes in AA rats. Hesperidin also restored the suppression of T-lymphocyte proliferation and IL-2 production, and downregulated production of IL-1, IL-6 and TNF-alpha by PM in AA rats. Our results suggest that hesperidin improves AA by downregulating the function of over-active macrophages and by up-regulating the activities of dysfunctional T lymphocytes. Hesperidin may therefore have therapeutic value for the clinical treatment of RA. Further research is required to clarify the detailed mechanisms of the protective effects of hesperidin on AA.
18344196 Effect of inflammation on kidney function and pharmacokinetics of COX-2 selective nonstero 2008 Oct Chronic arthritis adversely affects glomerular function and nonsteroidal anti-inflammatory drugs (NSAIDs) reduce electrolyte urinary excretion. In addition, both acute and chronic inflammations may alter clearance of drugs. We studied (a) the effects of inflammation on the renal function and pharmacokinetics of rofecoxib and meloxicam; (b) whether inflammation could exacerbate reduced electrolytes excretion changes observed with NSAIDs; and (c) the influence of inflammation on distribution of these drugs into the kidney. Single oral doses of rofecoxib (10 mg kg(-1)), meloxicam (3 mg kg(-1)) or placebo were administered to normal or pre-adjuvant arthritic rats. Blood and urine samples were collected for the measurement of plasma nitrite, BUN and creatinine. The urinary excretion of sodium and potassium was also determined. Nitrite, BUN and plasma creatinine were increased starting on day 9 in the groups with inflammation. Sodium and potassium excretion rates were not affected by inflammation. Meloxicam did not alter the electrolyte excretion in any of the groups. Rofecoxib significantly decreased sodium and potassium excretion in normal rats and potassium excretion in inflamed rats. Inflammation significantly increased plasma concentrations of rofecoxib, but not meloxicam. The ratios of the kidney:plasma concentrations were not significantly altered by inflammation following either drug. Inflammation altered kidney function, demonstrated by increases in BUN and plasma creatinine. However, it did not influence the urinary electrolytes excretion. Since we have observed similar patterns of the effect of NSAIDs on kidney under healthy and inflammatory conditions, one may conclude that inflammation does not exacerbate the adverse effect.
17926823 Rituximab: new indication. In rheumatoid arthritis: for a few patients, with close monitor 2007 Oct (1) Methotrexate is often used as a first-line treatment for severe and worsening rheumatoid arthritis. TNF alpha antagonists (etanercept, infliximab and adalimumab) are second-line options. (2) Rituximab, a monoclonal antibody first used to treat lymphoma, is now also approved for the treatment of rheumatoid arthritis when at least one TNF alpha antagonist has failed. (3) There are three available comparative trials including about 1150 rheumatoid arthritis patients. The results indicate that rituximab is no more effective than methotrexate; a combination of rituximab + methotrexate is more effective than methotrexate alone (although only about half the patients meet the ACR 20% response criterion); and adding a steroid fails to improve effectiveness. (4) The adverse effect profile of rituximab in arthritis seems similar to that observed in lymphoma. In the short term, the main adverse effects are infusion hypersensitivity reactions, which are more frequent during the first infusion and can be partly prevented by premedication with a steroid. The other known risks are mainly infectious and cardiovascular. Follow-up is too short to rule out a possible increase in the risk of cancer. Gastrointestinal perforations have occurred in some lymphoma patients treated with rituximab. (5) In practice, when standard treatment fails, adding rituximab to methotrexate can be beneficial but requires close patient monitoring.
17622600 Hydroxychloroquine and risk of diabetes in patients with rheumatoid arthritis. 2007 Jul 11 CONTEXT: Hydroxychloroquine, a commonly used antirheumatic medication, has hypoglycemic effects and may reduce the risk of diabetes mellitus. OBJECTIVE: To determine the association between hydroxychloroquine use and the incidence of self-reported diabetes in a cohort of patients with rheumatoid arthritis. DESIGN, SETTING, AND PATIENTS: A prospective, multicenter observational study of 4905 adults with rheumatoid arthritis (1808 had taken hydroxychloroquine and 3097 had never taken hydroxychloroquine) and no diagnosis or treatment for diabetes in outpatient university-based and community-based rheumatology practices with 21.5 years of follow-up (January 1983 through July 2004). MAIN OUTCOME MEASURES: Diabetes by self-report of diagnosis or hypoglycemic medication use. RESULTS: During the observation period, incident diabetes was reported by 54 patients who had taken hydroxychloroquine and by 171 patients who had never taken hydroxychloroquine, with incidence rates of 5.2 per 1000 patient-years of observation compared with 8.9 per 1000 patient-years of observation, respectively (P < .001). In time-varying multivariable analysis with adjustments for possible confounding factors, the hazard ratio for incident diabetes among patients who had taken hydroxychloroquine was 0.62 (95% confidence interval, 0.42-0.92) compared with those who had not taken hydroxychloroquine. In Poisson regression, the risk of incident diabetes was significantly reduced with increased duration of hydroxychloroquine use (P < .001 for trend); among those taking hydroxychloroquine for more than 4 years (n = 384), the adjusted relative risk of developing diabetes was 0.23 (95% confidence interval, 0.11-0.50; P < .001), compared with those who had not taken hydroxychloroquine. CONCLUSION: Among patients with rheumatoid arthritis, use of hydroxychloroquine is associated with a reduced risk of diabetes.
18728048 Evidence of epistasis between interleukin 1 and selenoprotein-S with susceptibility to rhe 2009 Sep OBJECTIVE: Selenoprotein-S (SELS) is involved in the stress response within the endoplasmic reticulum (ER) and inflammation. Recently, promoter variants in the SELS gene were shown to be associated with plasma levels of interleukin (IL)6, IL1beta and tumour necrosis factor (TNF). It was hypothesised that these variants could influence rheumatoid arthritis (RA) susceptibility and may interact with functional single nucleotide polymorphisms (SNPs) in the genes for IL1, IL6 and TNF. METHODS: Genotyping was performed in 988 unrelated healthy controls and 965 patients with RA. Stratified analysis was used to test for interactions. Single gene effects and evidence of epistasis were investigated using the Mantel-Haenszel (M-H) test and the linkage disequilibrium (LD)-based statistic. RESULTS: No association of SELS -105 genotype and RA susceptibility was detected. Stratification of SELS -105 genotypes by IL1 -511 genotypes showed that the disease risk (comparing AA/GA to GG at the SELS -105 locus) in individuals with the GG/AG genotype at the IL1beta -511 locus was significantly lower than that in individuals having the AA genotype at the IL1beta -511 locus (odds ratio (OR): 0.9 and 2.3, respectively; p = 0.004 by M-H test). Significant epistasis was also detected using the LD-based statistic (p = <0.001). No interaction was observed between SELS -105 and IL6 or TNF variants. CONCLUSION: Our results reveal evidence of strong epistasis in two genes in the IL1 production pathway and highlight the potential importance of gene-gene interactions in the pathogenesis of RA.
15645233 Influence of serum folic acid levels on plasma homocysteine concentrations in patients wit 2006 Jan The purpose of this study was to investigate whether negative effects of methotrexate (mtx) on blood homocysteine (hmc) levels can be prevented with the replacement of folic acid. 42 female patients with rheumatoid arthritis (RA) were studied. Patients were separated into two groups according to their treatment status with mtx (group I: 27 patients taking mtx and folic acid; group II: 15 patients not using mtx). The level of hmc was found to be 6.3+/-2.4 micromol/l in group I and 7.87+/-3.2 micromol/l in group II (p>0.05). Folic acid levels of group I and II were found to be 21.3+/-15.9 ng/ml and 8.41+/-2.86 ng/ml respectively (p<0.001). There was a statistically-significant correlation between age and hmc levels (r=0.386, p=0.012). Negative statistically-significant correlations were observed between folic acid and hmc levels. The effects of mtx on hmc can be prevented with the replacement of folic acid.
19043773 Developing of granulomatous thyroiditis during etanercept therapy. 2009 Jun We describe a 32-year-old man who developed granulomatous thyroiditis (GT) during etanercept therapy for rheumatoid arthritis (RA). Fever and thyroid pain developed 8 months after administration of etanercept. Noncaseating epithelioid cell granulomas consistent with GT were detected in a thyroid biopsy. Tissue staining and cultures for bacteria, mycobacterium, and fungus were all negative. Etanercept therapy was withdrawn and steroids regime was indicated with clinical and laboratory improvement. A month after, the patient developed hypothyroidism and recurrence of RA. A year after, the patient is asymptomatic with rituximab, methotrexate, and levothyroxine therapy. We report a case of GT probably in an etanercept-induced granulomatous reaction context.
16421645 Urticaria and angiedema-like skin reactions in a patient treated with adalimumab. 2007 May Specific inhibition of the cytokine tumor necrosis factor alpha has resulted in significant clinical and laboratory improvement of patients with chronic inflammatory diseases of Th1 phenotype. Etanercept is a recombinant fusion protein of two p75 soluble receptors, while infliximab is a chimeric monoclonal antibody. Both have been considered to be immunogenic and cause various immune-mediated skin reactions. On the other hand, adalimumab, a human monoclonal antibody, was expected to cause little or no immune-mediated skin reactions. Herein, we report a patient with rheumatoid arthritis treated with adalimumab, who after the seventh injection, developed angiedema affecting the lips and face, as well as an urticaria-like skin reaction affecting the trunk. These reactions were followed by hypotension. The patient was treated appropriately and after 2 h, the rashes and the edema disappeared and the patient gradually recovered completely. Adalimumab was discontinued.
19014836 Pharmacokinetic and pharmacodynamic properties of TRU-015, a CD20-directed small modular i 2008 Oct BACKGROUND: TRU-015 is a small modular immunopharmaceutical protein drug that binds to CD20 and effectively depleted B cells in nonhuman primates. OBJECTIVE: The aim of this clinical study was to determine the pharmacokinetic (PK) and pharmacodynamic (PD) properties, immunogenicity, and tolerability of TRU-015 in patients with rheumatoid arthritis (RA). METHODS: This Phase I, open-label, dose-escalation clinical study was conducted at 4 medical centers in the United States. Patients with RA who were receiving stable-dose methotrexate were enrolled in 1 of 8 dose groups and received TRU-015 as a single IV dose of 0.015, 0.05, 0.15, 0.5, 1.5, 5, or 15, or 2 IV doses of 15 mg/kg, administered 7 days apart (30 mg/kg). Patients were enrolled in the next higher dose cohort based on the tolerability observed in the prior cohort. Prior to TRU-015 infusion, patients were premedicated with an antihistamine and acetaminophen and may have received a corticosteroid at the investigator's discretion. Serum samples were collected for analysis of PK properties (serum t((1/2))) and neutralizing antibodies to TRU-015; enzyme-linked immunosorbent assays and a cell-based neutralizing assay were used to evaluate samples from patients. PD response was measured using B-cell (CD19(+)-cell) count using flow cytometry at prespecified time points. Tolerability was assessed during drug infusion and at prespecified time points after infusion using physical examination and laboratory analysis. Patients were followed for >or=4 weeks and until B-cell recovery. RESULTS: Thirty-seven patients were enrolled. Most were female (81%) and white (95%); the mean age was 53 years. Serum t((1/2)) ranged from 12 to 19 days. B-cell depletion generally increased in degree and duration with increasing doses. No neutralizing antibodies to TRU-015 were detected. Mild adverse events (AEs) included back pain, headache, peripheral edema, and upper respiratory infection (5 patients each). Mild urticaria occurred in 1 patient. Grade 3 AEs included hypertension, arthralgia, and urticaria and bronchospasm (1 patient each). No dose-limiting toxicity was found. CONCLUSIONS: In this small population of patients with RA, the C(max) and the AUC appeared to increase in a dose-proportional manner. The mean t((1/2)) ranged from 12 to 19 days. TRU-015 was associated with dose-dependent B-cell depletion and an acceptable tolerability profile.
18309376 Several regions in the major histocompatibility complex confer risk for anti-CCP-antibody 2008 May Recent evidence suggests that additional risk loci for RA are present in the major histocompatibility complex (MHC), independent of the class II HLA-DRB1 locus. We have now tested a total of 1,769 SNPs across 7.5Mb of the MHC located from 6p22.2 (26.03 Mb) to 6p21.32 (33.59 Mb) derived from the Illumina 550K Beadchip (Illumina, San Diego, CA, USA). For an initial analysis in the whole dataset (869 RA CCP + cases, 1,193 controls), the strongest association signal was observed in markers near the HLA-DRB1 locus, with additional evidence for association extending out into the Class I HLA region. To avoid confounding that may arise due to linkage disequilibrium with DRB1 alleles, we analyzed a subset of the data by matching cases and controls by DRB1 genotype (both alleles matched 1:1), yielding a set of 372 cases with 372 controls. This analysis revealed the presence of at least two regions of association with RA in the Class I region, independent of DRB1 genotype. SNP alleles found on the conserved A1-B8-DR3 (8.1) haplotype show the strongest evidence of positive association (P ~ 0.00005) clustered in the region around the HLA-C locus. In addition, we identified risk alleles that are not present on the 8.1 haplotype, with maximal association signals (P ~ 0.001-0.0027) located near the ZNF311 locus. This latter association is enriched in DRB1*0404 individuals. Finally, several additional association signals were found in the extreme centromeric portion of the MHC, in regions containing the DOB1, TAP2, DPB1, and COL11A2 genes. These data emphasize that further analysis of the MHC is likely to reveal genetic risk factors for rheumatoid arthritis that are independent of the DRB1 shared epitope alleles.
18548207 [Serial whole-body cryotherapy in the criostream for inflammatory rheumatic diseases. A pi 2008 Jun 15 BACKGROUND AND PURPOSE: Local as well as whole-body cryotherapy is used to relieve pain and inflammation in rheumatic diseases. In comparison with a chamber-based whole-body cryotherapy, the novel criostream whole-body therapy (single-person cabin with cold air cooled by liquid nitrogen) as an innovative technique offers not only a rapid therapeutic effect but also a considerable reduction in costs. The aim of this study was to compare the effect of whole-body cryotherapy in the criostream on pain reduction, disease activity and pro-inflammatory cytokines (tumor necrosis factor-[TNF-]alpha and interleukin-[IL-]1), and improvement in functional scores. PATIENTS AND METHODS: Ten patients with different active inflammatory rheumatic diseases (four patients with rheumatoid arthritis, three patients with ankylosing spondylitis, and three patients with psoriatic arthritis/spondylitis) underwent nine sessions of whole-body cryotherapy in 5 days for a short time period (at first 90 s, with step-up in each application to 2.5 min total time). RESULTS: Pain and disease activity scores decreased significantly, and, subsequently, also the functional scores showed a significant amelioration. Furthermore, there was a significant reduction in TNF-alpha (p < 0.01) and IL-1 (p < 0.05). Side effects were reported only after the first application in two cases (headache and sensation of cold). CONCLUSION: The criostream offers an elegant and, from the patient's point of view, attractive therapeutic agent in the multimodal treatment concept for inflammatory rheumatic diseases.
16437199 Temporomandibular disorders seen in rheumatology practices: A review. 2006 Jul Temporomandibular disorders are recognized as the most common nontooth-related chronic orofacial pain conditions. This article reviews the recent temporomandibular disorders literature and summarizes the temporomandibular disorders seen in rheumatology practices. Arthritis is a common condition affecting the temporomandibular joint. Although degenerative and rheumatoid arthritis are the most frequently encountered infectious arthritis, metabolic arthritis, spondyloarthropathies and the traumatic arthritis have also been reported. Distinguishing between different temporomandibular disorders is as important as the clinical course, long-term prognosis, and therapy. Diagnostic criteria are generally based on signs and symptoms of the patient. The American Academy of Orofacial Pain established the first well-defined diagnostic classification. In addition, Research Diagnostic Criteria for Temporomandibular Disorders have been developed using similar classification. In the treatment of temporomandibular disorders, conservative and noninvasive treatments are endorsed for the initial care of nearly all TMD patients because the majority of patients with TMD achieve good relief of symptoms with conservative treatment.