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ID PMID Title PublicationDate abstract
22826113 The long-term marriage between autoimmunity and internal medicine: a homage to Manuel Carl 2012 Dec Our understanding of autoimmune diseases results from the perfect combination of basic and clinical scientific research, and the figure that is closest to the proposed autoimmunology specialist is certainly the internist. The role of B cells in rheumatoid arthritis, the immunological mechanisms to fibrosis or to tissue specific damage, the classification of Bechet's syndrome, the clinical outcomes of antiphospholid syndrome, and new biomarkers for vascular complications in systemic sclerosis constitute, among others, are ideal examples of this combination. For these reason, this issue includes comprehensive reviews in all these areas and is dedicated to Dr. Manuel Carlos Dias and his career in the perfectioning and teaching of the clinical skills necessary to manage autoimmune disease. We are convinced that these discussions are likely of interest to basic scientists and clinicians alike for the proposed translational applications.
22665557 Odontoid pannus formation in a patient with ankylosing spondylitis causing atlanto-axial i 2012 Feb 25 Ankylosing spondylitis is one of the commonest inflammatory diseases of the axial skeleton and can be complicated by atlanto-axial instability. This serious and likely underestimated complication can be easily overlooked. However, there are clear features which can help alert suspicion to initiate the appropriate investigations with imaging that is very effective at diagnosing and assessing this complication. The authors report an unusual case where odontoid pannus formation, akin to that seen in rheumatoid arthritis, was the underlying cause.
23807906 B Cell in Autoimmune Diseases. 2012 The role of B cells in autoimmune diseases involves different cellular functions, including the well-established secretion of autoantibodies, autoantigen presentation and ensuing reciprocal interactions with T cells, secretion of inflammatory cytokines, and the generation of ectopic germinal centers. Through these mechanisms B cells are involved both in autoimmune diseases that are traditionally viewed as antibody mediated and also in autoimmune diseases that are commonly classified as T cell mediated. This new understanding of the role of B cells opened up novel therapeutic options for the treatment of autoimmune diseases. This paper includes an overview of the different functions of B cells in autoimmunity; the involvement of B cells in systemic lupus erythematosus, rheumatoid arthritis, and type 1 diabetes; and current B-cell-based therapeutic treatments. We conclude with a discussion of novel therapies aimed at the selective targeting of pathogenic B cells.
21921428 Fournier's gangrene in elderly patient: report of a case. 2011 Aug Fournier's gangrene (FG) is rapidly progressing acute gangrenous infection of the anorectal and urogenital area. FG needs precocious diagnosis and aggressive treatment with the use of wide spectrum antibioticus and surgical debridement. In our case, a 91-year-old Japanese female who had rehabilitation after treatment of pneumonia and her past history was rheumatoid arthritis treated with steroid and chronic heart failure. Her activities of daily living was bedridden with dementia. Necrotic skin was observed in urogenital and anorectal area and skin redness enlarged to the hip with high fever. Surgical debridement was performed. Both Peptostreptococcus Sp. and Fusobacterium Sp. was cultured from resected necrotic tissue. We used antibioticus, PAPM and PIPC, which had sensitivity for them. But unfortunately, disseminated intravascular coagulation occurred after 4th day of operation, and finally she died after 10th day of operation. We discussed the treatment for FG in patient with complication.
21681069 Pseudallescheria boydii infection of a prosthetic hip joint--an uncommon infection in a ra 2011 Sep Pseudallescheria boydii infection of the hip joint was diagnosed 2.5 years after implantation of a prosthetic joint in a woman with rheumatoid arthritis. Cure was achieved with a 10-month course of voriconazole coupled with removal of the prosthesis and repeat surgical debridement. Pseudallescheria boydii is an environmental mold that can cause osteoarticular infection, most often not only after local trauma but also after local injections and surgical procedures. Hip involvement was rarely reported, and this is the first description of a prosthetic joint infection with Scedosporium sp.
21661676 Single percutaneous injection of stromal cell-derived factor-1 induces bone repair in mous 2011 Jun Stromal cell-derived factor-1 is a dominant chemokine in bone marrow that is known to be involved in inflammatory diseases, including rheumatoid arthritis. Its role in bone repair has recently been demonstrated. The purpose of this study was to investigate the role of extraneous stromal cell-derived factor-1 in fracture healing.
20832177 Therapeutic potential of interleukin-6 antagonism in bipolar disorder. 2011 Jan Bipolar disorder (BD) is a chronic, severe, and highly disabling psychiatric disorder. Its underlying neurobiology remains largely unclear. A significant body of evidence indicates that inflammatory activation expressed by increased cytokines is relevant in its pathophysiology. IL-6 is one of the most important cytokines involved in the pathogenesis of immune and inflammatory disorders. Several studies recently showed increased levels of IL-6 in manic and depressive episodes and also during euthymia in subjects with BD. Tocilizumab is an IL-6 receptor antagonist being marketed for the treatment of rheumatoid arthritis and Castleman's disease. In this article we discuss the possibility that tocilizumab may have a therapeutic role in treatment of BD through its anti-inflammatory action.
22547902 Effects of long term polyarthritis and subsequent NSAID treatment on activity with disasso 2012 May 1 Chronic pain has profound effects on activity. Previous reports indicate chronic inflammatory conditions result in reduced activity which normalizes upon pain treatment. However, there is little systematic investigation of this process. Rheumatoid arthritis is an autoimmune disorder that causes significant joint pain. The K/BxN serum transfer mouse has been characterized as a model for rheumatoid arthritis and chronic pain. We investigated the activity of mice following K/BxN serum transfer vs. control serum and observed the activity changes following delivery of an NSAID, ketorolac. Previous studies have used running wheels and laser beams to monitor activity; we chose to validate a model using cost-effective infrared sensors on individual cages. Each mouse had its baseline activity obtained, which showed significant variation between individual C57Bl/6 mice. Arthritic mice had significantly decreased activity for only the first 11 nights. Conversely, previous work has shown that these animals display tactile allodynia that persists for at least 45 days. Mice were treated with ketorolac in their drinking water (10mg/kg, 15mg/kg, or 20mg/kg) for nights 6-8. The two highest doses showed significant normalization of activity levels. Four nights after ketorolac was stopped, treated animals were still significantly more active than control. The reversal of the reduced activity provides support that the depression relates to the arthritic pain state of the animal. These results indicate the efficacy of activity monitoring to better investigate behavior in persistent pain states. However, insofar as depressed activity reflects pain and disability, the present work raises questions as to the relevance of the tactile thresholds in defining behaviorally relevant pain states.
21905970 Further assessment of the clinically effective dose range of etoricoxib: a randomized, dou 2011 Oct OBJECTIVE: To further assess the clinically active dose range of etoricoxib, a COX-2 selective inhibitor, in rheumatoid arthritis (RA). METHODS: RA patients were randomized to etoricoxib 10, 30, 60, or 90 mg or placebo in a double-blind, 12-week study. DMARDs (methotrexate, biologics) or low-dose corticosteroids were allowed in stable doses. The primary endpoint was the proportion of patients completing the study and achieving an American College of Rheumatology 20% (ACR20) response. Secondary endpoints included individual components of the ACR index and Patient Global Assessment of Pain. Safety was assessed by physical exam and adverse experiences (AEs) occurrences. RESULTS: Etoricoxib 90 mg was the only dose to reach a statistically significant difference from placebo (p < 0.001) on the primary endpoint; etoricoxib 60 mg approached significance (p = 0.057). Significant pain improvement vs. placebo was observed with etoricoxib 90 mg (p < 0.001), 60 mg (p = 0.018), and 30 mg (p = 0.017). Despite the use of background biologics and corticosteroids, a dose response was still apparent. A higher proportion of etoricoxib 60 and 90 mg patients had renovascular AEs (i.e., edema and hypertension) compared with placebo, although discontinuations for renovascular AEs were rare. Etoricoxib 90 mg had a higher incidence of serious AEs (n = 5; 1 was considered drug-related) versus placebo (n = 0). LIMITATIONS: The present study was not powered to detect differences in cardiovascular or gastrointestinal safety by dose. Additionally, further research is needed to clarify the role of doses less than the etoricoxib 90 mg dose for pain management in RA patients. CONCLUSION: Etoricoxib 90 mg demonstrated statistically superior efficacy (ACR20) compared with placebo and numerical superiority over the other doses of etoricoxib studied. Etoricoxib 30 and 60 mg demonstrated significant pain improvement versus placebo, suggesting utility for some patients.
21310034 Factors predicting the outcome of customised foot orthoses in patients with rheumatoid art 2011 Feb 10 BACKGROUND: Conservative management of foot problems in patients with rheumatoid arthritis (RA) may consist of the prescription of customised foot orthoses. Indications for foot orthoses are not clear and the effectiveness of the intervention is highly variable among patients. Knowledge on which patients benefit the most from foot orthoses can help to select patients eligible for this type of intervention. The objective of the present study was to determine clinical and demographic factors that predict the outcome of customised foot orthoses on pain and disability in patients with RA. METHODS: A total of 135 RA patients who were supplied with customised foot orthoses were included in this prospective cohort study. Pain and disability were measured before and after the intervention period using a Numeric Rating Scale (NRS) for foot pain, the Foot Function Index (FFI), the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) and a 10-meter walking test. The intervention period consisted of one or more appointments with the podiatrist during which the foot orthoses were customised.Swollen foot joint count, foot deformity scores, forefoot peak pressure, disease duration, age, gender, body mass index and baseline values of the outcome measures were selected as potential factors predicting outcome. Multivariate linear regression analyses were performed to determine factors associated with change in pain and disability (at P < 0.05). RESULTS: Disease duration was negatively associated with the change scores in NRS foot pain (P = 0.018), WOMAC pain (P = 0.001), FFI disability (P = 0.003) and WOMAC physical function (P = 0.002). Age was negatively associated with the change score in 10 meter walking time (P = 0.008). For all outcome measures baseline values were positively associated with the change scores (P < 0.001). CONCLUSIONS: Shorter disease duration predicted greater improvements in self-reported foot pain and disability, and younger age predicted greater improvements in walking time after intervention with foot orthoses. Also, higher baseline values of pain and disability predicted greater improvements. Referral for conservative management with foot orthoses in the early stage of RA seems important when aiming to achieve reduction in pain and improvement in daily activities.
22550964 Pharmacokinetic and pharmacodynamic properties of canakinumab, a human anti-interleukin-1Π2012 Jun 1 Canakinumab is a high-affinity human monoclonal anti-interleukin-1β (IL-1β) antibody of the IgG1/κ isotype designed to bind and neutralize the activity of human IL-1β, a pro-inflammatory cytokine. Canakinumab is currently being investigated on the premise that it would exert anti-inflammatory effects on a broad spectrum of diseases, driven by IL-1β. This paper focuses on the analysis of the pharmacokinetic and pharmacodynamic data from the canakinumab clinical development programme, describing results from the recently approved indication for the treatment of cryopyrin-associated periodic syndromes (CAPS) under the trade name ILARIS®, as well as diseases such as rheumatoid arthritis, asthma and psoriasis. Canakinumab displays pharmacokinetic properties typical of an IgG1 antibody. In a CAPS patient weighing 70 kg, slow serum clearance (0.174 L/day) was observed with a low total volume of distribution at steady state (6.0 L), resulting in a long elimination half-life of 26 days. The subcutaneous absolute bioavailability was high (70%). Canakinumab displays linear pharmacokinetics, with a dose-proportional increase in exposure and no evidence of accelerated clearance or time-dependent changes in pharmacokinetics following repeated administration was observed. The pharmacokinetics of canakinumab in various diseases (e.g. CAPS, rheumatoid arthritis, psoriasis or asthma) are comparable to those in healthy individuals. No sex- or age-related pharmacokinetic differences were observed after correction for body weight. An increase in total IL-1β was observed in both healthy subjects and all patient populations following canakinumab dosing, reflecting the ability of canakinumab to bind circulating IL-1β. The kinetics of total IL-1β along with the pharmacokinetics of canakinumab were characterized by a population-based pharmacokinetic-binding model, where the apparent in vivo dissociation constant, signifying binding affinity of canakinumab to circulating IL-1β, was estimated at 1.07 ± 0.173 nmol/L in CAPS patients. During development of canakinumab a cell line change was introduced. Pharmacokinetic characterization was performed in both animals and humans to assure that this manufacturing change did not affect the pharmacokinetic/pharmacodynamic properties of canakinumab.
22112624 Forefoot pathology in rheumatoid arthritis identified with ultrasound may not localise to 2011 Nov 23 BACKGROUND: Plantar pressures are commonly used as clinical measures, especially to determine optimum foot orthotic design. In rheumatoid arthritis (RA) high plantar foot pressures have been linked to metatarsophalangeal (MTP) joint radiological erosion scores. However, the sensitivity of foot pressure measurement to soft tissue pathology within the foot is unknown. The aim of this study was to observe plantar foot pressures and forefoot soft tissue pathology in patients who have RA. METHODS: A total of 114 patients with established RA (1987 ACR criteria) and 50 healthy volunteers were assessed at baseline. All RA participants returned for reassessment at twelve months. Interface foot-shoe plantar pressures were recorded using an F-Scan® system. The presence of forefoot soft tissue pathology was assessed using a DIASUS musculoskeletal ultrasound (US) system. Chi-square analyses and independent t-tests were used to determine statistical differences between baseline and twelve months. Pearson's correlation coefficient was used to determine interrelationships between soft tissue pathology and foot pressures. RESULTS: At baseline, RA patients had a significantly higher peak foot pressures compared to healthy participants and peak pressures were located in the medial aspect of the forefoot in both groups. In contrast, RA participants had US detectable soft tissue pathology in the lateral aspect of the forefoot. Analysis of person specific data suggests that there are considerable variations over time with more than half the RA cohort having unstable presence of US detectable forefoot soft tissue pathology. Findings also indicated that, over time, changes in US detectable soft tissue pathology are out of phase with changes in foot-shoe interface pressures both temporally and spatially. CONCLUSIONS: We found that US detectable forefoot soft tissue pathology may be unrelated to peak forefoot pressures and suggest that patients with RA may biomechanically adapt to soft tissue forefoot pathology. In addition, we have observed that, in patients with RA, interface foot-shoe pressures and the presence of US detectable forefoot pathology may vary substantially over time. This has implications for clinical strategies that aim to offload peak plantar pressures.
21435026 Safety of treatment with biologics for psoriasis in daily practice: 5-year data. 2012 Mar BACKGROUND: The cumulative exposition to biologics is increasing with prolonged treatment with a certain biologic or consecutive biological treatment. However, long-term safety data are limited available. OBJECTIVES: The aim of this study was to prospectively evaluate the 5-year safety of biological treatment for psoriasis in daily practice. METHODS: A cohort of 173 psoriasis patients on biologics was prospectively followed for 5 years. All adverse events reported were documented and analysed. Primary endpoint was the percentage of patients reporting at least one serious adverse event. The rate of malignancies, serious infections and serious cardiovascular events was compared with the general population incidence rate. The nature and rate of dermatological adverse events was compared with a group of prospectively followed rheumatoid arthritis patients on TNF-α blocking therapy. RESULTS: Between February 2005 and April 2010, 173 patients were enrolled in the registry and went through a total number of 263 treatment episodes. The total number of patient-years of follow-up in the registry was 409. The number of patient-years was the highest for etanercept. Forty-nine patients (28%) reported 88 serious adverse events. Only one serious adverse event was certainly causally related to the biologic and 21 events (24% of SAEs) were considered possibly related. The incidence of malignancies, serious infections and serious cardiovascular events was comparable with the population incidence rate, except for skin malignancies. The incidence of skin malignancies was significantly higher than the general population incidence rate. The nature and rate of dermatological adverse events differed from the rheumatoid arthritis cohort. CONCLUSIONS: In this cohort, the safety of biological therapies for psoriasis was favourable with a low incidence of therapy-related serious adverse events.
22703762 Polymorphism in the TNF-alpha gene promoter at position -1031 is associated with increased 2012 Nov OBJECTIVES: Tumour necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine which is associated with the pathogenesis of many inflammatory diseases. The aim of this study was to investigate the effect of TNF-alpha -1031 gene polymorphism on circulating TNF-alpha, myeloperoxidase (MPO) and nitrotyrosine (NT) levels in primary Sjögren's syndrome patients. METHODS: TNF-alpha-1031 T/C gene polymorphism was evaluated in 65 Sjögren's syndrome patients and 58 age and gender matched controls via 5' nuclease PCR analysis. Plasma TNF-alpha and NT levels were analysed by ELISA while MPO activity, total nitrate/nitrite and glutathione (GSH) levels were measured by spectral analysis. RESULTS: TNF-alpha -1031 C carrier genotype frequency was significantly higher (p=0.045) in Sjögren patients compared to controls (23.1 vs. 10.3%, 0R= 2.83, 95% CI=0.27-7.8). Plasma TNF-alpha concentration and NT levels were also significantly higher in Sjögren patients with -1031 C carrier genotype compared to patients with TT genotype. Sjögren patients showed a significant increase in plasma MPO activity which correlated with both TNF-alpha and NT levels in subjects with -1031 C carrier genotype assessed by linear regression analysis. TNF-alpha-1031 T/C gene polymorphism had no effect on plasma nitrate/nitrite and GSH levels which were significantly decreased in Sjögren's syndrome patients compared to controls. CONCLUSIONS: Polymorphism in the TNF-alpha gene promoter at position -1031 is associated with increased circulating levels of TNF-alpha which is correlated with increased plasma MPO activity and protein nitration in Sjögren's syndrome.
21288453 [Effects of Drynaria total flavonoids on apoptosis of osteoblasts mediated by tumor necros 2011 Feb OBJECTIVE: To investigate the influence of Drynaria total flavonoids on proliferation and apoptosis of osteoblasts in tumor necrosis factor-α (TNF-α)- mediated medium, so as to explore the mechanism of Drynaria total flavonoids in preventing and treating osteoporosis of rheumatoid arthritis. METHODS: Twenty Wistar rats with average weight of (200±20) g were randomly divided into two groups: blank control group and Qianggu capsule (Drynaria total flavonoids) group. Rats in Qianggu capsule group were fed with 75 mg Qianggu capsule daily for continuous 3 d. One hour after the last feed, blood samples were collected. The in vitro experiment of four groups was designed: blank control serum group, Drynaria total flavonoids-containing serum group, blank control serum plus TNF-α group and Drynaria total flavonoids-containing serum plus TNF-α group. Methyl thiazolyl tetrazolium method was used to detect the proliferation of osteoblasts. Flow cytometry was used to detect the apoptosis of osteoblasts and real-time fluorescent quantitative polymerase chain reaction to detect the expressions of Bcl-2 and Bax mRNAs in osteoblasts. RESULTS: Compared with the control serum, Drynaria total flavonoids-containing serum promoted the proliferation and decreased the apoptosis of osteoblasts in TNF-α-mediated inflammatory environment (P<0.05), and increased the ratio of Bcl-2 mRNA to Bax mRNA. CONCLUSION: In TNF-α-mediated inflammatory environment, Drynaria total flavonoids can promote the proliferation and decrease the apoptosis of osteoblasts by improving the ratio of Bcl-2 mRNA to Bax mRNA, which may be one of the mechanisms of Drynaria total flavonoids in preventing and treating osteoporosis of rheumatoid arthritis.
22988304 Use of population based background rates of disease to assess vaccine safety in childhood 2012 Sep 17 OBJECTIVES: To predict the number of selected outcomes temporally associated but not caused by vaccination, to aid causality assessment of adverse events arising after mass immunisation in a paediatric population. DESIGN: Nationwide population based cohort study. SETTING: Denmark. PARTICIPANTS: All liveborn infants delivered after 1 January 1980. Study population was followed from date of birth until hospital admission for selected outcome diagnoses, death, first emigration, age 18 years, or 31 December 2009. The study population was subject to vaccines used in standard childhood immunisation in Denmark, with 82-93% vaccine coverage. MAIN OUTCOME MEASURES: Incidence of acute infectious and post-infectious polyneuritis (Guillain-Barré syndrome), acute transverse myelitis, optic polyneuritis, facial nerve palsy, anaphylactic shock, seizure, multiple sclerosis, autoimmune thrombocytopenia, type 1 diabetes mellitus, juvenile and rheumatoid arthritis, narcolepsy, and death of unknown cause stratified by sex, age, and season. We predicted the number of events for a hypothetical vaccine cohort of 1,000,000 people for follow-up periods of up to 182 days. RESULTS: The study included 2,300,227 liveborn infants, yielding 37,262,404 person years of follow-up; median follow-up was 16.8 person years. Incidence of outcome diagnoses spanned from 0.32 per 100,000 patient years for autoimmune thrombocytopenia to 189.82 per 100,000 patient years for seizure. Seasonal differences were most pronounced for anaphylactic shock, seizure, and multiple sclerosis. Even for rare outcomes, numerous events were predicted in the hypothetical vaccine cohort. We predicted that 20 cases of type 1 diabetes mellitus, 19 of juvenile or rheumatoid arthritis, eight of facial nerve palsy, and five of multiple sclerosis per 1,000,000 children would occur within 42 days after vaccination. CONCLUSIONS: Incorporating exact background rates of disease based on age, sex, and seasonal distribution could strengthen vaccine safety assessment, and provides an evidence based focus for discussing the incremental risk of newly introduced vaccines.
21518967 Role of asymmetrical dimethylarginine in inflammation-induced endothelial dysfunction in h 2011 Jul We explored the role of asymmetrical dimethylarginine (ADMA) as a cause of endothelial dysfunction induced by systemic inflammation. In vitro data suggest that ADMA bioavailability is regulated by proinflammatory stimuli, but it is unclear whether ADMA is a link between inflammation and endothelial dysfunction in humans. In study 1 we recruited 351 patients with coronary artery disease (CAD) and 87 healthy controls. In study 2 we recruited 69 CAD, 69 healthy, and 10 patients with rheumatoid arthritis, whereas in study 3, 22 healthy and 70 CAD subjects were randomly assigned to Salmonella typhii vaccination (n=11 healthy and n=60 CAD) or placebo (n=11 healthy and n=10 CAD). Circulating interleukin 6/ADMA and flow-mediated dilation (FMD) were measured at 0 and 8 hours. In study 1, ADMA was inversely correlated with FMD in healthy individuals and CAD patients (P<0.0001 for both). However, interleukin 6 was inversely correlated with FMD (P<0.0001) in healthy subjects but not in CAD patients. The positive correlation between ADMA and interleukin 6 was stronger in healthy (r=0.515; P<0.0001) compared with CAD (r=0.289; P=0.0001) subjects. In study 2, both patients with rheumatoid arthritis and CAD had higher interleukin 6 (P<0.0001) and ADMA (P=0.004) but lower FMD (P=0.001) versus healthy subjects. In study 3, vaccination increased interleukin 6 in healthy (P<0.001) and CAD (P<0.001) subjects. FMD was reduced in healthy subjects (P<0.05), but its reduction in CAD was borderline. Vaccination increased ADMA only in healthy subjects (P<0.001). Systemic, low-grade inflammation leads to increased ADMA that may induce endothelial dysfunction. This study demonstrated that ADMA may be a link between inflammation and endothelial dysfunction in humans.
22896022 Rheumatic disease among Oklahoma tribal populations: a cross-sectional study. 2012 Oct OBJECTIVE: Rheumatic diseases cause significant morbidity within American Indian populations. Clinical disease presentations, as well as historically associated autoantibodies, are not always useful in making a rapid diagnosis or assessing prognosis. The purpose of our study was to identify autoantibody associations among Oklahoma tribal populations with rheumatic disease. METHODS: Oklahoma tribal members (110 patients with rheumatic disease and 110 controls) were enrolled at tribal-based clinics. Patients with rheumatic disease (suspected or confirmed diagnosis) were assessed by a rheumatologist for clinical features, disease criteria, and activity measures. Blood samples were collected and tested for common rheumatic disease autoantibodies [antinuclear antibody (ANA), anti-cyclic citrullinated peptide antibodies (anti-CCP), rheumatoid factor (RF), anti-Ro, anti-La, anti-Sm, anti-nRNP, anti-ribosomal P, anti-dsDNA, and anticardiolipins]. RESULTS: In patients with suspected systemic rheumatic diseases, 72% satisfied American College of Rheumatology classification criteria: 40 (36%) had rheumatoid arthritis (RA), 16 (15%) systemic lupus erythematosus, 8 (7%) scleroderma, 8 (7%) osteoarthritis, 4 (4%) fibromyalgia, 2 (2%) seronegative spondyloarthropathy, 1 Sjögren's syndrome, and 1 sarcoidosis. Compared to controls, RA patient sera were more likely to contain anti-CCP (55% vs 2%; p < 0.001) or RF IgM antibodies (57% vs 10%; p < 0.001); however, the difference was greater for anti-CCP. Anti-CCP positivity conferred higher disease activity scores (DAS28 5.6 vs 4.45; p = 0.021) while RF positivity did not (DAS28 5.36 vs 4.64; p = 0.15). Anticardiolipin antibodies (25% of rheumatic disease patients vs 10% of controls; p = 0.0022) and ANA (63% vs 21%; p < 0.0001) were more common in rheumatic disease patients. CONCLUSION: Anti-CCP may serve as a more specific RA biomarker in American Indian patients, while the clinical significance of increased frequency of anticardiolipin antibodies needs further evaluation.
22059987 Vasoactive intestinal peptide/vasoactive intestinal peptide receptor relative expression i 2011 Dec Sjögren's syndrome (SS) is a chronic autoimmune disease characterized by a progressive oral and ocular dryness that correlates poorly with the autoimmune damage of the glands. It has been proposed that a loss of homeostatic equilibrium in the glands is partly responsible for salivary dysfunction with acinar cells involved actively in the pathogenesis of SS. The non-obese diabetic (NOD) mouse model of Sjögren's syndrome develops secretory dysfunction and early loss of glandular homeostatic mechanisms, with mild infiltration of the glands. Based on the vasodilator, prosecretory and trophic effects of the vasoactive intestinal peptide (VIP) on acini as well as its anti-inflammatory properties we hypothesized that the local expression of VIP/vasoactive intestinal peptide receptor (VPAC) system in salivary glands could have a role in acinar cell apoptosis and macrophage function thus influencing gland homeostasis. Here we show a progressive decline of VIP expression in submandibular glands of NOD mice with no changes in VPAC receptor expression compared with normal mice. The deep loss of endogenous VIP was associated with a loss of acinar cells through apoptotic mechanisms that could be induced further by tumour necrosis factor (TNF)-α and reversed by VIP through a cyclic adenosine-5'-monophosphate (cAMP)/protein kinase A (PKA)-mediated pathway. The clearance of apoptotic acinar cells by macrophages was impaired for NOD macrophages but a shift from inflammatory to regulatory phenotype was induced in macrophages during phagocytosis of apoptotic acinar cells. These results support that the decline in endogenous VIP/VPAC local levels might influence the survival/apoptosis intracellular set point in NOD acinar cells and their clearance, thus contributing to gland homeostasis loss.
21865696 Reactive arthritis induced by tonsillitis: a type of 'focal infection'. 2011 OBJECTIVE: The clinical manifestation of reactive arthritis (ReA ) induced by tonsillitis is demonstrated. METHODS: Medical records of 21 patients with ReA induced by tonsillitis were analyzed. RESULTS: Nine male and 12 female patients were recorded. The mean age was 31.7 years ranging from 20 to 51 years. The mean duration of arthritis was 29.8 months (2 weeks to 10 years). Acute or recurrent origoarthritis involved in ankle, knee and sternoclavicular joints associated with Achilles tendon enthesitis were demonstrated. Thirteen of 21 (62%) patients were demonstrated positive for ASO and/or ASK. Group A streptococcus was demonstrated in 12 of 21 (57.1%) patients and other bacteria were demonstrated by culture of tonsillar swab or from resected tonsillar microabscess. No bacteria was demonstrated in synovial fluid from 3 patients. Rheumatoid factor was demonstrated only in 2 of 21 patients. HLA-B39 and BW61 (B40) were significantly demonstrated in 5 and 7 patients (p=0.0004, 0.0006, respectively) compared with those of healthy controls. All patients were treated with antibiotics and nonsteroidal anti-inflammatory drugs (NSAIDs). Eight of 21 patients underwent tonsillectomy. Arthritis ceased after the treatments and no recurrence was found. DISCUSSION: Sterile inflammatory arthritis induced by tonsillitis was cured by resection of the microabscess in the tonsils. Therefore, ReA induced by tonsillitis is one form of 'focal infection'.