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ID PMID Title PublicationDate abstract
20943067 Large granular lymphocyte leukemia with pure red cell aplasia associated with autoimmune p 2010 Jul Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a recessively inherited monogenic disease caused by a mutation in the autoimmune regulator (AIRE) gene. AIRE plays a major role in central (thymic) immune tolerance. In the absence of AIRE, autoimmunity develops that is especially targeted at endocrine tissues. T-cell large granular lymphocyte (T-LGL) leukemia is a monoclonal lymphoproliferative disease characterized by persistent and indolent lymphocytosis. Autoimmune manifestations, such as rheumatoid arthritis or autoimmune cytopenia, are also common. We report the case of a patient with APECED, who presented with pure red cell aplasia associated with T-LGL leukemia. The association of T-LGL leukemia and APECED is very rare and may not be fortuitous. The immunological mechanisms of this association are discussed.
20669554 [Pulmonary arterial hypertension in connective tissue diseases]. 2009 Nov Among connective tissue diseases, pulmonary arterial hypertension (PAH) is frequently associated with systemic sclerosis and systemic lupus erythematosus. PAH is less common in mixed connective tissue diseases and Sjögren's syndrome, and rare in rheumatoid arthritis. PAH in systemic sclerosis may be either isolated (prevalence about 8%) or associated with interstitial lung disease. Echocardiographic screening for PAH is worthwhile in patients with systemic sclerosis, especially as treatments for idiopathic PAH (endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostanoids) are effective in this setting. The prevalence of PAH among patients with systemic lupus erythematosus is poorly known; immunosuppressive treatment is sometimes effective by itself but most patients benefit from PAH treatment. PAH associated with connective tissue diseases has a worse prognosis than idiopathic PAH.
20450057 [Progress in Tripterygium wilfordiiand its bioactive components in the field of pharmacody 2010 Feb In the trials of multi-glycoside of Tripterygium wilfordii (GTW) in the field of pharmacodynamics, some clinical characteristics and symptoms, such as proteinuria, hematuria,joint pain, and skin damage, could be improved in the patients with various diseases including proliferative glomerulonephritis, lupus nephritis, rheumatoid arthritis, psoriasis and other immune-related diseases. In this review, it has been also reported to discuss the effects of GTW and Triptolide (T4), which is a bioactive component in GTW on anti-inflammatory, immunosuppression, and protection of epithelial cell in kidney. On the other hand, it is possible to have some beneficial effects on organ transplant rejection, tumor growth and anti-fertility.
20411438 Peripheral neuropathy masquerading as an epidural complication. 2012 Mar BACKGROUND: Epidural anaesthesia generally provides safe postoperative pain control, but does carry a small risk of nerve damage. CASE DESCRIPTION: A 30-year-old woman with long standing rheumatoid arthritis underwent a primary total knee replacement under general anaesthetic. Postoperatively, a continuous epidural infusion was used for pain relief. On discontinuation of the epidural, she was confirmed to have a foot drop. Her subsequent investigation and management for neuropathic pain was coordinated by the acute pain service. Magnetic resonance imaging excluded a central lesion. Nerve conduction studies 6 weeks later confirmed peripheral nerve lesions. The patient's neurological deficit was not due to her epidural, but rather her intraoperative tourniquet. DISCUSSION: The episode raises a number of discussion points for our pain service around the use of epidurals for knee replacement surgery, the management of nerve injury and the ease at which the epidural can be blamed for coincident injuries. International evidence would suggest that neurological complications following knee replacement are more likely to be related to surgery can epidural analgesia.
20013267 Anti-TNF therapies: a comprehensive analysis of adverse effects associated with immunosupp 2011 Mar Knowledge and understanding about the immunosuppressive properties of anti-TNF therapies and the adverse effects these causes have advanced over the last 10 years since the first of these drugs was approved. These drugs work by inhibiting tumour necrosis factor (TNF) in the body, which plays an essential role in the immune response to invading pathogens. Anti-TNF drugs have therapeutic value because high levels of TNF are thought to be part of the pathophysiology of many chronic inflammatory disorders such as rheumatoid arthritis and Crohn's disease. Anti-TNF drugs are usually well-tolerated, however, there have been reports of many potentially serious adverse effects. This article will comprehensively analyse these adverse effects; the incidence, symptoms and mechanisms will be discussed. In addition, the contraindications of this class of drugs will be explored and the detection and prevention methods that should be put in place by health care professionals who treat patients on these drugs will be described.
19946298 B-cell-depletion therapy in SLE--what are the current prospects for its acceptance? 2009 Dec Analogous to the successful introduction of biologic agents to treat rheumatoid arthritis, it was widely envisaged that similar successful studies would follow in systemic lupus erythematosus (SLE), as much was known about the etiopathogenesis of the disease and appropriate agents to block the key cells and molecules were available. The reality, however, has been different. The failure of rituximab, a monoclonal antibody that induces B-cell depletion, to meet its primary and secondary end points in trials of nonrenal SLE (EXPLORER) and renal (LUNAR) lupus nephritis has been disappointing given the success reported in many open-label studies. Concluding that B-cell-depletion therapy is not effective in SLE seems rather extreme. Further analysis of the as-yet unpublished results and their comparison with data from published studies might provide insight into whether B-cell depletion will eventually be accepted as a useful approach for the treatment of SLE.
19689388 3D-pharmacophere models for CC chemokine receptor 1 antagonists. 2009 Jul The CC Chemokine Receptor 1 (CCR1) is closely related to various chronic inflammatory diseases like rheumatoid arthritis and multiple sclerosis, and plays a crucial role in transplant rejection. Inhibiting its activity with CCR1 antagonists has been proved to be effective in preventing some diseases. A number of in vivo experiments have been carried out to shed light on the underlying mechanism of the interactions between the CCR1 and its ligands. However, their conclusions are still controversial. In this study, ligand-based computational drug design is applied as a new and effective way to study the structure-activity relationship of CCR1 antagonists. Three-dimensional pharmacophore models were generated for CCR1 antagonists, using both HypoGen and HipHop algorithms in Catalyst software. Two optimal pharmacophore models were defined through careful qualification processes. Both of them have four features: one hydrogen-bond acceptor, one positive ionable and two hydrophobic groups. Additional information was obtained through comparison between the two models. Our results can be valuable tools for the discovery and development of specific, highly potent CCR1 antagonists. For Supplement material, please see the online version of the article.
19508226 Recognition of the N-terminal histone H2A and H3 peptides by peptidylarginine deiminase IV 2009 Peptidylarginine deiminase IV (PAD4) catalyzes the conversion of an Arg residue to a citrulline residue in various proteins. In particular, citrullination of histone subunits, such as H2A and H3, by PAD4 is thought to be related to rheumatoid arthritis. However, the details of the citrullination mechanism of histone H2A and H3 are not yet well known. Moreover, the effects of N-terminal acetylation on histone subunits with respect to PAD4 recognition have not yet been studied. To further study the mechanism of PAD4 recognition of histone H2A and H3 subunits, a series of the N-terminal peptides was chemically synthesized and the citrullination sites were identified using MALDI-TOF/MS. N-terminal acetylation of histone H2A was not significant with respect to PAD4 recognition in vitro, but the acetylation of H3 peptide had a significant effect on PAD4 recognition in vitro, resulting in predominant citrullination at the Arg2 residue.
19382482 [Pathological study on autopsy died of Tripterygium intoxication--report of 4 cases]. 2009 Feb The Tripterygium preparation, a Chinese herbal medicine, has been widely used to treat various autoimmune diseases, such as rheumatoid arthritis and systemic lupus erythematosus. Its significant clinical effects have received a great praise and attention by the public health in China, but its toxicity also definitely exists, with the therapeutic dosage approaching the minimal toxic dosage. In order to provide reference for the safe use of Tripterygium preparation in clinical practice, the pathological changes of 4 autopsy cases by Tripterygium poisoning were reported in this paper. In them, 2 cases died of acute cardiogenic shock caused by myocardial damage, showing hydropic degeneration of the myocardial cells, even with obvious contraction band necrosis in the papillary muscles; the other 2 died of severe acute renal failure due to severe acute toxic nephrosis; cerebral edema and gastrointestinal inflammatory changes were found in all cases. The authors suggested that careful dosage control is the key step to prevent Tripterygium intoxication during the medical treatments; directly using the crude Tripterygium in clinics should be prohibited; and the Tripterygium preparation used should be produced by the pharmaceutical companies regulated by the government.
19369735 Connective tissue growth factor (ctgf) expression in the tenosynovium of patients with car 2009 Connective Tissue Growth Factor (CTGF) expression has been identified in a wide variety of fibrotic disorders; however, the expression of CTGF in carpal tunnel syndrome (CTS) has not yet been described in the literature. Both inflammatory and fibrotic etiologies have been implicated in the pathogenesis of CTS, with current evidence favoring an emphasis on a non-inflammatory fibrosis pathophysiological picture. Our objective was to identify whether CTGF is expressed in the tenosynovium of patients with CTS. Tenosynovial tissue was isolated from human subjects undergoing surgical decompression of the carpal tunnel (carpal tunnel release or CTR) for treatment of CTS following various durations of failed conservative management. Samples tested included patients with "idiopathic" CTS alone or CTS in the presence of associated co-orbidities including Type II Diabetes Mellitus (DM), Rheumatoid Arthritis (RA), and Systemic Lupus Erythematosus (SLE). SDS-PAGE protein analysis of tenosynovial tissue homogenate was performed to assess for differences in overall protein expression amongst all samples. Our findings demonstrate the presence varying levels of CTGF in tenosynovial samples from patients with CTS. Additionally, tenosynovial samples from patients with certain associated comorbidities - specifically RA and SLE - exhibit significant upregulation of CTGF levels relative to the levels observed patients with "idiopathic" CTS. These findings indicate that there is likely to be a role for CTGF in the pathogenesis of CTS.
19330784 Small-molecule inhibitors of store-operated calcium entry. 2009 May Controlled variation in intracellular calcium concentration is a key component of the immune response signaling pathway in lymphocytes. Store-operated calcium entry (SOCE) in these cells provides a prolonged increase in cytoplasmic Ca(2+) concentrations and ultimately leads to the production of pro-inflammatory cytokines. Molecules that inhibit SOCE could therefore be useful immunomodulating agents for the treatment of rheumatoid arthritis, psoriasis, inflammatory bowel disease, and other conditions. Although the presence of the SOCE signaling pathway in lymphocytes and other cells involved in the immune response has been known for many years, key proteins involved in SOCE were identified only recently. The identification of these proteins may further enable the identification of agents that inhibit SOCE without affecting other cellular processes. This contribution documents representative examples of the small-molecule inhibitors of SOCE that have been reported to date. Where possible, methods that were used to characterize the mechanism of action of the inhibitors are also described.
19297127 [Treatment of systemic autoimmune and inflammatory diseases with rituximab]. 2009 May Rituximab is a chimeric monoclonal antibody that targets CD20 antigen at the surface of B lymphocytes. The efficacy of rituximab in patients with rheumatoid arthritis has been demonstrated in 3 randomized controlled trials. Rituximab is now used in a wide range of systemic autoimmune and inflammatory diseases, as it is well tolerated and efficient. Adverse events are scarce, consisting mainly in reactions during infusion and infectious complications that are favoured by the association of rituximab therapy with other immunosuppressants. Relapses of the disease are common around six months after rituximab infusion. The response to retreatment with rituximab is usually the same that was obtained after the first course of treatment.
19275604 Soluble forms of RAGE in human diseases: clinical and therapeutical implications. 2009 The ligand - receptor for advanced glycation end-products (RAGE) axis has emerged as a novel pathway involved in a wide spectrum of diseases, including diabetes mellitus, atherothrombosis, chronic renal failure, rheumatoid arthritis, neurodegeneration, cancer and aging. Circulating soluble forms of RAGE (sRAGE), arising from receptor ectodomain shedding and splice variant [endogenous secretory (es) RAGE] secretion, may counteract RAGE-mediated pathogenesis, by acting as a decoy. Several studies suggest that decreased levels of sRAGE and/or esRAGE may be useful as a biomarker of ligand-RAGE pathway hyperactivity and inadequate endogenous protective response, thus providing a powerful complement to cardiovascular risk stratification and an interesting target of therapeutic interventions. This review will focus on the pathophysiological determinants of soluble forms of RAGE in different clinical settings, with particular reference to the mechanisms involved in their generation and clearance, the association with cardiovascular risk factors, the interplay with low-grade inflammation, oxidative stress and endothelial dysfunction, and the possible pharmacological modulation of their plasma levels.
19219907 Testing homogeneity of two zero-inflated Poisson populations. 2009 Feb The problem of testing treatment difference in the occurrence of a safety parameter in a randomized parallel-group comparative clinical trial under the assumption that the number of occurrence follows a zero-inflated Poisson (ZIP) distribution is considered. Likelihood ratio tests (LRT) for homogeneity of two ZIP populations are derived under the hypotheses that (i) there is no difference in inflation parameters, (ii) there is no difference in non-zero means; and (iii) there is no difference in both inflation parameters and non-zero means. Approximate formulas for sample size calculation are also obtained for achieving a desired power for detecting a clinically meaningful difference under the corresponding alternative hypotheses. An example concerning the assessment of the gastrointestinal (GI) safety in terms of the number of erosion counts of a newly developed compound for the treatment of osteoarthritis and rheumatoid arthritis is given for illustration purpose.
21629437 Genetics of interleukin 1 receptor-like 1 in immune and inflammatory diseases. 2010 Dec Interleukin 1 receptor-like 1 (IL1RL1) is gaining in recognition due to its involvement in immune/inflammatory disorders. Well-designed animal studies have shown its critical role in experimental allergic inflammation and human in vitro studies have consistently demonstrated its up-regulation in several conditions such as asthma and rheumatoid arthritis. The ligand for IL1RL1 is IL33 which emerged as playing an important role in initiating eosinophilic inflammation and activating other immune cells resulting in an allergic phenotype.An IL1RL1 single nucleotide polymorphism (SNP) was among the most significant results of a genome-wide scan investigating eosinophil counts; in the same study, this SNP associated with asthma in 10 populations.The IL1RL1 gene resides in a region of high linkage disequilibrium containing interleukin 1 receptor genes as well as interleukin 18 receptor and accessory genes. This poses a challenge to researchers interested in deciphering genetic association signals in the region as all of the genes represent interesting candidates for asthma and allergic disease.The IL1RL1 gene and its resulting soluble and receptor proteins have emerged as key regulators of the inflammatory process implicated in a large variety of human pathologies We review the function and expression of the IL1RL1 gene. We also describe the role of IL1RL1 in asthma, allergy, cardiovascular disease, infections, liver disease and kidney disease.
21462768 A rare case of scurvy in an otherwise healthy child: diagnosis through oral signs. 2010 Nov The purpose of this paper was to report the case of a 2-year-old Caucasian female who was referred with a presumed diagnosis of pediatric rheumatoid arthritis. The patient presented widespread gingival swelling with bleeding, sharp pain, and halitosis. The patient also presented pain and swelling of the right knee joint, and psychomotor restlessness associated with muscular frailty. Little compliance on the part of both the patient and parents was also noted. Oral manifestations, together with an accurate medical history, led to the diagnosis of infantile scurvy, caused by an inadequate dietary supply of vitamin C. Administering 250 mg of ascorbic acid orally twice a day led to the remission of gingival swelling and of the other symptoms. The parents were advised to feed the child appropriate foods. Nutritional problems are traditionally linked to an insufficient availability of food, but can also be associated with child- or family-related psychological problems.
19842993 Antibodies to mutated citrullinated vimentin and antibodies to cyclic citrullinated peptid 2009 BACKGROUND: The goal of the study was to assess the presence of antibodies to mutated citrullinated vimentin (anti-MCV) and cyclic citrullinated peptides (anti-CCP) in patients with juvenile idiopathic arthritis (JIA) compared with patients with other juvenile onset rheumatic diseases. METHODS: The study included 56 patients who fulfilled the International League of Associations for Rheumatology (ILAR) classification criteria for JIA, and 17 control patients with other juvenile onset rheumatic diseases. Data on six core outcome variables and the Sharp score were collected for patients with JIA. Sera and synovial fluid, if available, were tested for anti-CCP and anti-MCV antibodies using a commercial enzyme-linked immunosorbent assay (ELISA). RESULTS: Anti-MCV antibodies were positive in 3/56 (5.4%) and anti-CCP in 1/56 (1.8%) of patients with JIA. Two out of three anti-MCV positive patients (one of them also anti-CCP positive) were found to be rheumatoid factor (RF)-positive with polyarticular disease. Within the control group, anti-MCV was positive in 4/17 (23.5%) patients, while anti-CCP positivity was not observed. No correlation between anti-MCV with anti-CCP antibody levels was found for any of the six core outcome variables or for the adapted Sharp score. CONCLUSIONS: Our results show that antibodies targeting citrullinated proteins are not a useful diagnostic marker for JIA, but can indicate severe patterns of disease in JIA.
21185106 Wnt signaling in macrophages: augmenting and inhibiting mycobacteria-induced inflammatory 2011 Jun Wnt proteins are secreted, palmitoylated glycoproteins with multiple functions in cell proliferation and migration as well as tissue organization. They are best known for their role in embryonic development and tissue homeostasis. In the last years, Wnt signaling was also shown to be involved in the regulation of inflammatory processes: Wnt5a is induced in human macrophages in response to mycobacteria and conserved bacterial structures and contributes to the regulation of pro-inflammatory cytokines via its receptor Frizzled (Fzd) 5. Wnt5a is also induced in other infectious and inflammatory diseases such as tuberculosis, sepsis, psoriasis, rheumatoid arthritis and atherosclerosis. In contrast, Wnt3a, a ligand of Fzd1, is constitutively expressed by bronchial epithelial cells and mediates anti-inflammatory effects on mycobacteria-infected macrophages via the Wnt/beta-Catenin signaling pathway. This pathway suppresses the activity of GSK3beta, a well known regulator of NF-kappaB-dependent gene transcription. Here we review recent data on immunomodulatory activities of Wnt proteins. Additional experiments using exogenous Wnt homologs further support the notion that TLR/NF-kappaB and Wnt signaling are functionally interconnected.
21179602 Practical considerations on the use of rituximab in autoimmune neurological disorders. 2010 Mar Rituximab (Mabthera, Rituxan) is a chimeric human/murine monoclonal antibody against CD-20 surface antigen expressed on B-cells. Rituximab, by causing B-cell depletion, appears to be effective in several autoimmune disorders; it has been approved for rheumatoid arthritis and is a promising new agent in the treatment of several autoimmune neurological disorders. A controlled study in patients with relapsing remitting multiple sclerosis has shown that rituximab significantly reduces the number of new MRI lesions and improves clinical outcome; it also showed some promise in a subset of patients with primary progressive MS. The drug is also effective in a number of patients with Devic's disease, myasthenia gravis, autoimmune neuropathies, and inflammatory myopathies. The apparent effectiveness of rituximab has moved B-cells into the center stage of clinical and laboratory investigation of autoimmune neurological disorders. We review the evidence-based effectiveness of rituximab in neurological disorders based on controlled trials and anecdotal reports, including our own experience, and address the immunobiology of B-cells in autoimmune central nervous system (CNS) and peripheral nervous system (PNS) disorders. In addition, we provide practical guidelines on how best to use this drug in clinical practice and highlight its potential toxicity.
21094504 Molecular analyses of the Chinese herb Leigongteng (Tripterygium wilfordii Hook.f.). 2011 Jan Tripterygium wilfordii Hook.f., known as Leigongteng (Thunder God Vine) in traditional Chinese medicine, has attracted much attention for its applications in relieving autoimmune disorders such as rheumatoid arthritis and systemic lupus erythematosus, and for treating cancer. Molecular analyses of the ITS and 5S rDNA sequences indicate that T. hypoglaucum and T. doianum are not distinct from T. wilfordii, while T. regelii should be recognized as a separate species. The results also demonstrate potential value of rDNA sequence data in forensic detection of adulterants derived from Celastrus angulatus in commercial samples of Leigongteng.