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

ID PMID Title PublicationDate abstract
19657722 No significant association between Fc receptor-like 3 gene polymorphisms and human leukocy 2010 Jan Ankylosing spondylitis (AS) is a rheumatoid arthritis, which is a common autoimmune disease with a complex genetic etiology. Although HLA-B27 has been identified to be associated with AS, a number of other genes may also be involved in the disease. Fc receptor-like 3 (FCRL3) gene has been shown to be associated with rheumatoid arthritis in Japanese population. Here we aim to explore the association FCRL3 gene and susceptibility to human leukocyte antigen (HLA)-B27-positive AS in Han Chinese population. Among 169 AS patients, the frequencies of C and T (rs7522061) in FCRL3 gene were 38.7 and 61.3%, respectively; in 184 controls (HLA-B27-positive), the frequencies of C and T were 38.6 and 61.4%, respectively. The frequencies of alleles and genotype are not of statistically significant difference in two groups (chi(2) = 0.000, P = 0.983; chi(2) = 0.099, P = 0.952, respectively), but the distribution of HLA-B27 subtypes are statistically significant difference between cases and controls (chi(2) = 8.214, P = 0.042). Our data reveal that the FCRL3 gene does not appear associated with susceptibility to HLA-B27-positive AS in Han Chinese population.
19442310 Clinical audit of foot problems in patients with rheumatoid arthritis treated at Counties 2009 May 15 BACKGROUND: At diagnosis, 16% of rheumatoid arthritis (RA) patients may have foot joint involvement, increasing to 90% as disease duration increases. This can lead to joint instability, difficulties in walking and limitation in functional ability that restricts activities of daily living. The podiatrist plays an important role in the multidisciplinary team approach to the management of foot problems. The aim of this study was to undertake a clinical audit of foot problems in patients with RA treated at Counties Manukau District Health Board. METHODS: Patients with RA were identified through rheumatological clinics run within CMDHB. 100 patients were eligible for inclusion. Specific foot outcome tools were used to evaluate pain, disability and function. Observation on foot lesions were noted and previous history of foot assessment, footwear/insoles and foot surgery were evaluated. RESULTS: The median age of the cohort was 60 (IQR: 51-64) years old with median disease duration of 15 (IQR: 7.3-25) years. Over 85% presented with foot lesions that included corns and callus over the forefoot region and lesser toe deformities. Moderate to high disability was noted. High levels of forefoot structural damage were observed. 76% had not seen a podiatrist and 77% reported no previous formal foot assessment. 40% had been seen at the orthotic centre for specialised footwear and insoles. 27% of RA patients reported previous foot surgery. A large proportion of patients wore inappropriate footwear. CONCLUSION: This clinical audit suggests that the majority of RA patients suffer from foot problems. Future recommendations include the provision of a podiatrist within the current CMDHB multidisciplinary rheumatology team to ensure better services for RA patients with foot problems.
19132794 Rheumatoid arthritis and fibromyalgia: a frequent unrelated association complicating disea 2009 Jan OBJECTIVE: To assess the value of the 28-joint Disease Activity Score (DAS28) in evaluating disease activity in rheumatoid arthritis (RA) associated with fibromyalgia (FM). In this situation, because of the weight of the subjective measures included in the DAS28 equation, the patient's status may be overestimated, leading to inappropriate treatment. We analyze the relationship between RA and FM and discuss whether the association is random or a marker of poor prognosis. METHODS: A questionnaire, developed when biologic therapies were introduced, was administered and the results analyzed in a consecutive, female outpatient population including 105 patients with RA, 49 with RA and FM (RAF), and 28 with FM. Psychosocial characteristics, disease presentation, and radiographic joint destruction evaluation were compared in the 3 populations. RESULTS: The presentation of RA was the same in patients with RA and RAF, but the 2 populations differed by socioprofessional characteristics, significantly higher disease activity in patients with RAF, and significantly more severe joint destruction in patients with RA. The RAF group was similar to the FM control population in socioprofessional and some physical characteristics. Regression analysis using the DAS28 measures differed significantly in the weight allowed to 28-joint counts for pain and swelling, but the constant factor was higher in patients with RAF. CONCLUSION: DAS28 overestimated objective RA severity in patients who also had FM. The association between RA and FM does not appear to be a marker of worse prognosis, but rather a fortuitous association between the 2 diseases and one that may afford these patients some protection against joint destruction.
19054824 Effects of Porphyromonas gingivalis on cell cycle progression and apoptosis of primary hum 2009 Dec BACKGROUND: It has been suggested that bacterial infections have a role in the pathogenesis of rheumatoid arthritis (RA). P gingivalis, a Gram-negative, anaerobic rod, is one of the major pathogens associated with periodontal disease. OBJECTIVE: To examine P gingivalis infection and its effects on cell cycle progression and apoptosis of human articular chondrocytes. METHODS: Primary human chondrocytes cultured in monolayers were challenged with P gingivalis. Infection and invasion of P gingivalis into chondrocytes was analysed by scanning electron microscopy, double immunofluorescence and by antibiotic protection and invasion assay. Cell cycle progression of infected chondrocytes was evaluated by flow cytometry. Also, cell apoptosis was visualised by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL) of DNA strand breaks and by western blot analysis. RESULTS: Data showed that P gingivalis could adhere and infect primary human chondrocytes. After chondrocyte infection, intracellular localisation of P gingivalis was noted. Flow cytometry analyses demonstrated affected cell cycle progression, with an increase of the G(1) phase and a significant decrease of the G(2) phase after infection. In addition, increased apoptosis of P gingivalis-infected chondrocytes was visualised by TUNEL assay and by upregulation of caspase-3 protein expression. CONCLUSION: These data demonstrate that P gingivalis infects primary human chondrocytes and affects cellular responses, which might contribute to the tissue damage seen in the pathogenesis of rheumatoid arthritis.
20032098 EQ-5D and SF-36 quality of life measures in systemic lupus erythematosus: comparisons with 2010 Feb OBJECTIVE: The Medical Outcomes Study Short-form 36 (SF-36) provides numerical measurement of patient health, but does not include preferences for health states and cannot be used directly in cost-effectiveness analyses. By contrast the Euroqol EQ-5D can be used for cost-effectiveness analyses. The EQ-5D has rarely been used in systemic lupus erythematosus (SLE). We compared SF-36 and EQ-5D values across rheumatic diseases. METHODS: We studied 1316 patients with SLE, 13,722 with rheumatoid arthritis (RA), 3623 with non-inflammatory rheumatic disorders (NIRD), and 2733 with fibromyalgia (FM). RESULTS: The mean EQ-5D, physical (PCS) and mental (MCS) component summary scores were 0.72, 36.3, and 44.3, respectively, in SLE. There was essentially no difference among EQ-5D and PCS scores for patients with SLE, RA, or NIRD. MCS was lower in SLE compared with RA and NIRD (44.3, 49.1, 50.8, respectively). All scores were more abnormal in FM (0.61, 31.9, 41.9). Within SF-36 domains, physical function was better, but general health, vitality, social function, role-emotional, and mental health were more impaired in SLE compared with RA and NIRD. In SLE, quality of life (QOL) was predicted by damage, comorbidity, income, education, and age. Fifteen percent of patients with SLE were very satisfied with their health, and their QOL scores (0.84, 45.4, 50.1) were similar to those found in the US population for EQ-5D and MCS, but were slightly reduced for PCS. CONCLUSION: EQ-5D and PCS are at the same levels in SLE as in RA and NIRD, but are more abnormal in SLE in the MCS and mental health domains. EQ-5D values allow preference-based comparisons with other chronic conditions.
19533138 Antibodies directed to cyclic citrullinated peptides in familial Mediterranean fever. 2010 Feb The aim of this study was to find the prevalence of anti-cyclic citrullinated peptide (anti-CCP) in patients with familial Mediterranean fever (FMF) and to examine the relationship between anti-CCP and joint findings. We measured the serum levels of the anti-CCP antibodies in patients with FMF (n = 55) and healthy controls (n = 43). Serum levels of rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), fibrinogen, ferritin, erythrocyte sedimentation rate (ESR), and white blood cell (WBC) were also measured in all the samples. Fibrinogen, ferritin, erythrocyte sedimentation rate (ESR), and RF levels were normal in the patient and the control groups (P > 0.05). There was a significant difference in anti-CCP between the patient and the control groups (P = 0.008). There was a positive correlation between arthritis and anti-CCP (P = 0.001). In patients without arthritis, there was no significant relationship between abdominal pain or fever and anti-CCP (P > 0.05). Anti-CCP levels increased in FMF patients with arthritis independent from acute phase reactants such as CRP, ESR, and fibrinogen. We conclude that in patients who are under investigation for arthritis, the ones with positive anti-CCP and negative RF, may be examined for FMF. In addition, we also conclude that it is very likely that FMF patients with anti-CCP antibodies will have signs of arthritis. On the other hand, it is possible that long-term follow-up of the FMF patients with anti-CCP antibodies may reveal the eventual development of inflammatory joint disease.
21265467 Anti-arthritic activity of synthesized chondroitin sulfate E hexasaccharide. 2010 The purpose of this study was to investigate the anti-arthritic effects of synthesized chondroitin sulfate E hexasaccharide (sCSE-6, CAS 866407-73-0), using a type II collagen-induced arthritis model in mice. sCSE-6 was administered subcutaneously on a daily basis to type II collagen (CII)-sensitized mice from day 0 to day 55. The severity of arthritis, as well as the immunohistological features of the arthritic mice, were analyzed. sCSE-6 inhibited the course of arthritis and restored the body weight loss of CII-immunized mice. An immunohistological analysis showed that bone/cartilage destruction in the arthritic mice was significantly attenuated by sCSE-6 treatment, with a marginal inhibition of synovial inflammation also observed. The beneficial effect of sCSE-6 on bone destruction, which is the most important factor in preventing arthritis, is particularly noteworthy. In summary, sCSE-6 inhibited arthritis and helped to prevent bone and cartilage destruction in a type II collagen-induced arthritis model in mice. The findings indicated that CSE oligosaccharides might be a novel potential therapeutic tool for rheumatoid arthritis.
19885711 Septic arthritis in adults with sickle cell disease often is associated with osteomyelitis 2010 Jun BACKGROUND: Septic arthritis is a known complication of sickle cell disease (SCD) in children, and the association with osteomyelitis and osteonecrosis has been described. However, it is unclear whether this association applies to adults. QUESTIONS/PURPOSES: We therefore asked whether septic arthritis is a frequent complication in adults with SCD and whether it also is associated with osteomyelitis or osteonecrosis. METHODS: We retrospectively reviewed the charts of 2000 consecutive adult patients diagnosed with SCD and recorded symptoms, select findings during physical examination, laboratory data, and select radiographic CT, and MRI observations. RESULTS: Fifty-nine of the 2000 patients (3%) had septic arthritis, 56 of the 59 patients had hemoglobin SS. Thirty-six of the 59 infections (61%) were in the hip. The most frequent findings were pain, swelling, fever greater than 38.2 degrees C (71% of cases), a leukocyte count exceeding 15,000/mm(3) (range, 7900-32,300/mm(3)), a Westergren sedimentation rate greater than 24 mm/hour, and C-reactive protein exceeding 20 mg/L. Cultures were positive in 96% of the joint aspirates. Staphylococcus and Gram-negative infection predominated; no patients had Salmonella joint infections. Preexisting factors of bacterial arthritis included osteonecrosis (29 patients) and osteomyelitis (37 cases) in childhood. Diabetes, rheumatoid arthritis, glucocorticoids, and immunoparesis related to medical treatment by hydroxyurea were associated comorbidities. CT and MRI confirmed the diagnosis of associated osteonecrosis or osteomyelitis and allowed joint aspiration and detection of soft tissue abscess. CONCLUSIONS: The incidence of septic arthritis in adults with SCD is low, but often is associated with osteomyelitis or osteonecrosis. LEVEL OF EVIDENCE: Level II, prognostic study. See Guidelines for Authors for a complete description of levels of evidence.
19242063 IL-1beta in irrigation fluid and mRNA expression in synovial tissue of the knee joint as t 2009 OBJECTIVE: We studied the relationship between the severity of inflammation and IL-1beta production and relative expression level of IL-1beta mRNA in irrigation fluid and synovial tissue obtained from the knee joint during the acute stage of a murine model of type II collagen antibody-induced arthritis (CAIA). This model is used to identify potential therapeutic markers for treating rheumatoid arthritis. METHODS: Irrigation fluid and synovium tissue were harvested from the knee joint of BALB/c mice in acute stage of CAIA induction. The IL-1beta protein level was measured by enzyme-linked immunosorbent assay, and the relative expression level of IL-1beta mRNA was analyzed by reverse transcription-polymerase chain reaction. Two investigators analyzed expression levels and histopathological changes. RESULTS: IL-1beta concentration was higher in irrigation fluid from the knee joint than in the serum in the acute stage of CAIA. The relative expression level of IL-1beta mRNA was elevated in synovial tissue. Histopathological changes in the knee joint and foot indicated similar severity. CONCLUSIONS: IL-1beta concentration in irrigation fluid and relative expression level of IL-1beta mRNA in the synovium have potential as therapeutic markers in studying and treating CAIA.
19337686 Pre-operative irreducible C1-C2 dislocations: intra-operative reduction and posterior fixa 2009 May BACKGROUND: According to Menezes' algorithm, pre-operative dynamic neuroradiological investigation in C1-C2 dislocations (C1C2D) instability is strongly advocated in order to exclude those patients not eligible for posterior fixation and fusion without previous anterior trans-oral decompression. Anterior irreducible compression due to C1C2D instability, it is said, needs trans-oral anterior decompression. We reviewed our experience in order to refute such a paradigm. METHODS: The study involves 23 patients who were operated on for cranio-vertebral junction (CVJ) instability; all of them had C1C2D of varying degree on x-ray, computerised tomography (CT) and magnetic resonance (MR) imaging of the CVJ. Pre-operatively, irreducible C1C2D was demonstrated only in 3 patients, (2 with Down's Syndrome, one of them was harbouring os odontoideum, 1 Rheumatoid Arthritis), i.e. 13.04%; the remaining 19 (86.9%) had reducible C1-C2 dislocation. After an unsuccessful traction test conducted in the pre-operative phase under sedation, it was possible to completely reduce the C1C2D (with a combination of axial traction with light extension of the neck on the chest and a light flexion of the head on the neck by using a Mayfield head holder) and proceed to posterior fixation in all the patients under general anaesthesia using a precise "timing sequences fixation technique". Wiring (C0 and C3 were fixed first being stretched up to approximately 10 lbs, then C2 in order to pull up this vertebra last by forcing approximately 8 lbs) or screw fixation methods were used to achieve fusion along with post-operative external orthosis and neuroradiological assessment of the C1C2D. The instrumentation produced a lever and pulley effect which assisted reduction of the dislocation. FINDINGS: At follow up (range 34-55 months-mean 45.33 months) the clinical picture was improved or stable in all patients. CONCLUSIONS: Pre-operative irreducibility of the C1C2D should not be an absolute indication for trans-oral decompression. An attempt to reduce the dislocation under general anaesthesia and during posterior fixation should be attempted in Down's syndrome, os odontoideum and rheumatoid arthritis.
20093202 Pharmacological profile of AW-814141, a novel, potent, selective and orally active inhibit 2010 Apr The p38 mitogen activated protein kinase (MAPK) is a key signaling molecule that plays a crucial role in the progression of various inflammatory diseases such as rheumatoid arthritis (RA), asthma and chronic obstructive pulmonary disease. The objective of the present study was to evaluate the anti-inflammatory activity of a p38 MAPK inhibitor, AW-814141. AW-814141 inhibited enzymatic activity of recombinant p38-alpha and beta isoforms with IC(50) value of 100nM and 158nM, respectively. AW-814141 also inhibited the release of tumor necrosis factor (TNF)-alpha by lipopolysaccharide (LPS) treated human peripheral blood mononuclear cells with an IC(50) value of 212nM and demonstrated selectivity against a panel of few kinases. Oral administration of AW-814141 (10mpk) in LPS-injected mice resulted in a significant reduction in TNF-alpha production in the circulation. In a carrageenan-induced rat paw edema model and collagen-induced arthritis model (CIA), AW-814141 dose dependently inhibited paw swelling. In different in vivo efficacy models, efficacy of AW-814141 was found to be better as compared to the reference compounds (Vx-745 and BIRB-796). This study demonstrated that AW-814141 is a novel p38 MAPK inhibitor and it displays promising in vitro and in vivo anti-inflammatory activities and can be used for the treatment of rheumatoid arthritis.
19213589 Subaxial cervical vertebrae in patients with juvenile idiopathic arthritis--something spec 2009 Oct OBJECTIVES: To describe the main dimensions of the cervical vertebrae and spinal canal in two groups with juvenile idiopathic arthritis (JIA) and a non-inflammatory control group. METHODS: There were altogether 158 female patients in three different groups included in the study: a group with severe, complicated JIA (sJIA), a population based JIA group (pJIA), and fibromyalgia patients as a non-inflammatory control group (pFM). The patients' clinical records and cervical spine radiographs taken in adult age (>17 years) were evaluated. RESULTS: The patients with sJIA had the mean area of the 3rd-6th cervical vertebrae bodies and the average width and height of the 3rd-6th cervical vertebrae bodies significantly smaller than the patients in the pJIA and pFM groups. The mean value of the maximal difference between the successive vertebral body areas of each individual was significantly larger in the sJIA group than the other groups (p=0.047; the body height adjusted). There were no significant differences in the mean diameter of the sagittal spinal canal between study groups. CONCLUSIONS: Inflammatory changes of the cervical spine are common, and growth disturbances of cervical vertebrae in patients with JIA have been described previously. We found that patients with severe complicated JIA have a smaller cervical vertebral body size in general. They also have more differences in the sizes of their own vertebrae, representing growth disturbances of individual vertebral bodies. This is probably caused by the inflammatory disease and/or its more aggressive pharmacotherapy. The spinal canal diameter was only slightly smaller in the sJIA group. Thus the disturbed growth of the vertebral body in sJIA does not, in general, increase the risk of spinal canal compression.
19834062 Local interleukin-1-driven joint pathology is dependent on toll-like receptor 4 activation 2009 Nov Toll-like receptors (TLRs) may contribute to the pathogenesis of chronic inflammatory destructive diseases through the recognition of endogenous ligands produced on either inflammation or degeneration of the extracellular matrix. The presence of endogenous TLR agonists has been reported in rheumatoid joints. In the present study, we investigated the significance of TLR2 and TLR4 activation by locally- produced endogenous ligands in the severity of joint inflammation and destruction. Local joint pathology independent of systemic immune activation was induced by overexpression of interleukin (IL)-1 and TNF in naive joints using adenoviral gene transfer. Here, we report that at certain doses, IL-1-induced local joint inflammation, cartilage proteoglycan depletion, and bone erosion are dependent on TLR4 activation, whereas TLR2 activation is not significantly involved. In comparison, tumor necrosis factor alpha-driven joint pathology seemed to be less dependent on TLR2 and TLR4. The severity of IL-1-induced bone erosion and irreversible cartilage destruction was markedly reduced in TLR4(-/-) mice, even though the degree of inflammation was similar, suggesting uncoupled processes. Furthermore, the expression of cathepsin K, a marker for osteoclast activity, induced by IL-1beta was dependent on TLR4. Overexpression of IL-1beta in the joint as well as ex vivo IL-1 stimulation of patellae provoked the release of endogenous TLR4 agonists capable of inducing TLR4-mediated cytokine production. These data emphasize the potential relevance of TLR4 activation in rheumatoid arthritis, particularly with respect to IL-1-mediated joint pathology.
20863997 Fatal tuberculous myositis in an immunocompromised adult with primary Sjögren's syndrome. 2010 Sep Tuberculous myositis, which mimics rheumatic symptoms, is an extremely rare disease. Clinical ambiguity easily leads to misdiagnosis and delayed initial treatment. We present the case of a 55-year-old man who had primary Sjögren's syndrome and active cutaneous vasculitis treated with steroid and immunosuppressive drugs. He presented with a swollen, painful, hot left thigh. Although anti-tuberculosis medications were administered soon after a positive acid-fast stain of incisional muscular tissue, he died of rapidly progressive tuberculous myositis and multiorgan failure following 18 days of hospitalization. This case is presented to increase the awareness of this rare entity in clinical practice.
20693261 United Kingdom Primary Sjogren's Syndrome Registry--a united effort to tackle an orphan rh 2011 Jan Primary SS (pSS) is a multi-system autoimmune disease with a prevalence and health economic impact that are comparable with RA. However, pSS research has been relatively poorly supported. The creation of a large cohort of clinically well-characterized pSS patients will provide a catalyst and valuable resources to promote high-quality pSS research. In this review, we will describe the creation of such a cohort and the associated research biobank that is currently being established in the UK--entitled United Kingdom Primary Sjögren's Syndrome Registry (UKPSSR). We will discuss the strengths and weaknesses of the design of the registry and highlight the key challenges in the establishment of the registry and the strategies that we employ to overcome these barriers. Finally, we will consider the future development of the UKPSSR including utilization and maintenance of the cohort.
20185532 Aberrant localization of ezrin correlates with salivary acini disorganization in Sjogren's 2010 May OBJECTIVES: To analyse whether the alterations in the structure and organization of microvilli in salivary acinar cells from SS patients are linked to changes in the expression and/or cellular localization of ezrin. METHODS: Salivary gland (SG) acini from controls and SS patients were used to evaluate ezrin expression by western blot and localization of total and activated (phospho-Thr567) ezrin by IF and EM. RESULTS: In acini from control labial SGs, ezrin was located predominantly at the apical pole and to a lesser extent at the basal region of these cells. Conversely, in acini extracts from SS patients, ezrin showed significantly elevated levels, which were accompanied with localization mostly at the basal region. Moreover, F-actin maintained its distribution in both the apical region and basolateral cortex; however, it was also observed in the acinar cytoplasm. Phospho-ezrin (active form) was located exclusively at the apical pole of acinar cells from control subjects and abundantly located at the basal cytoplasm in SS samples. These results were confirmed by immunogold studies. CONCLUSIONS: The decrease of ezrin and phospho-ezrin at the apical pole and the cytoplasmic redistribution of F-actin suggest an altered interaction between the F-actin-cytoskeleton and plasma membrane in SS patient acini, which may explain the microvilli disorganization. These alterations could eventually contribute to SG hyposecretion in SS patients.
20101429 Successful treatment of refractory adult Still's disease and membranous glomerulonephritis 2010 Apr Adult onset Still's Disease (ASD) is a systemic inflammatory disorder of unknown etiology characterized by chronic and fluctuant fever with accompanying rash, polyarthritis and involvement of multiple organs, especially lymphoid tissues. Although kidney involvement may appear in some cases of adult Still's disease, membranous glomerulonephyritis has not been described before. We herein report a 38-year-old man diagnosed with Still's disease with longstanding polyarthritis unresponsive to high-dose steroids and various immunosuppressive drugs for 5 years. He was referred to our clinic with bilateral pretibial edema on his legs. Urine examination revealed 10.5 g/day proteinuria with membranous glomerulonephritis and his renal biopsy came up with it. Infliximab was initiated, and his complaints were totally resolved also with a normal urine test in the following 3 months. To the best of our knowledge, this is the first report that clearly shows the efficacy of infliximab in a patient with refractory ASD with membranous glomerulonephyritis.
20222952 Gait changes precede overt arthritis and strongly correlate with symptoms and histopatholo 2010 INTRODUCTION: Pristane-induced arthritis (PIA) in the rat has been described as an animal model of inflammatory arthritis which exhibits features similar to rheumatoid arthritis in humans, such as a chronic, destructive, and symmetrical involvement of peripheral joints. However, so far little is known about the earliest inflammatory events and their influence on locomotor behaviour during the course of PIA. To investigate this issue a detailed analysis of the pathologic changes occurring during the prodromal and early stages of PIA was performed. METHODS: Arthritis was induced in DA.rats by injection of 150 microl 2,6,10,4-tetramethyl-pentadecane (pristane) at the base of the tail and changes in locomotor behaviour of the affected paws were monitored using the CatWalk quantitative gait analysis system. The pathologic events occurring in the joints of pristane-injected animals were studied before onset, at onset, and during acute phase of arthritis by histological methods. RESULTS: Gait analysis revealed that changes in locomotion such as reduced paw print areas and stance phase time are already apparent before the onset of clinically discernible arthritis symptoms (erythema, paw swelling) and correlate with PIA scores. In agreement with these findings, inflammatory tenosynovitis could be observed by histology already before the onset of erythema and swelling of the respective paws. In the most heavily affected rats also irregularities in step sequence patterns occurred A kinetic analysis of clinical and histological findings demonstrated that gait changes precede the pathological changes occurring during the acute phase of pristane-induced arthritis. CONCLUSIONS: Gait analysis allows for pinpointing the initial inflammatory changes in experimental arthritis models such as pristane-induced arthritis. Analysis of early clinically relevant symptoms in arthritis models may facilitate the search for novel therapeutics to interfere with pain, inflammation and joint destruction in patients suffering from inflammatory arthritis.
19922019 S100A9 is not essential for disease expression in an acute (K/BxN) or chronic (CIA) model 2009 Nov OBJECTIVE: S100A8 (calgranulin A, MRP8) and S100A9 (calgranulin B, MRP14) are calcium-binding proteins highly expressed by activated myeloid cells and thought to be involved in the pathogenesis of inflammatory diseases. Circulating levels of S100A8/S100A9 are elevated in both human and experimental models of autoimmune disease, including rheumatoid arthritis (RA). METHODS: Mice deficient in S100A9 (S100A9 - /-) and wild-type controls were immunized using standard techniques for the K/BxN serum transfer or the collagen-induced arthritis (CIA) model. RESULTS: S100A9 - /- animals, with defective expression of both S100A8 and S100A9 proteins, had similar arthritis and histopathology to that of wild-type controls in both mouse models. CONCLUSION: S100A8 and S100A9 are not essential for disease expression in either the K/BxN serum transfer or the CIA model of inflammatory arthritis.
20851508 [Small fibre neuropathy: Diagnostic approach and therapeutic issues, and its association w 2010 Oct This article reviews the diagnostic issues and the therapeutic management of small fibre neuropathy (SFN), and a detailed literature analysis of its association with primary Sjögren's syndrome (pSS). A diagnosis of SFN should be raised in the presence of diffuse neuropathic painful manifestations (burning sensation, paresthesia, pricking, allodynia or hyperesthesia) and neurovegetative signs. The neurological examination and the electroneuromyogram are usually normal. The diagnosis of SFN can be confirmed by the evidence of decreased intra-epidermal nerve fibre density after a skin punch biopsy or the presence of abnormal nonconventional neurophysiological tests exploring the A-delta and C small nerve fibres (laser-evoked potentials, quantitative sensory tests, cutaneous sympathic reflex, autonomic function tests). The association of SFN and pSS has been scarcely evaluated, probably because of its lack of awareness and the low availability of the required diagnostic procedures. According to our literature review, pSS may be present in 9 to 30% of patients with SFN. Conversely, a pure SFN is present in 3 to 9% of patients with pSS where it may represent 25 to 35% of pSS-associated peripheral neuropathies. The treatment of SFN is mainly symptomatic and based on antalgic neuropsychotropic drugs and conventional analgesics. Corticosteroids and immunosuppressive drugs are usually unsuccessful. The effectiveness of intravenous immunoglobulins is only supported by a few case reports. SFN deserves to be separately evaluated among pSS-associated peripheral neuropathies. This requires a better availability of the appropriate diagnostic procedures, the investigation of underlying immunopathological mechanisms and the assessment of the new treatments recently proposed in pSS, mainly rituximab.