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ID PMID Title PublicationDate abstract
22400103 Spondyloarthropathies in autoimmune diseases and vice versa. 2012 Polyautoimmunity is one of the major clinical characteristics of autoimmune diseases (ADs). The aim of this study was to investigate the prevalence of ADs in spondyloarthropathies (SpAs) and vice versa. This was a two-phase cross-sectional study. First, we examined the presence of ADs in a cohort of patients with SpAs (N = 148). Second, we searched for the presence of SpAs in a well-defined group of patients with ADs (N = 1077) including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and Sjögren's syndrome (SS). Among patients with SpAs, ankylosing spondylitis was observed in the majority of them (55.6%). There were two patients presenting with SS in the SpA group (1.4%) and 5 patients with autoimmune thyroiditis (3.5%). The global prevalence of ADs in SpAs was 4.86%. In the ADs group, there were 5 patients with SpAs (0.46%). Our results suggest a lack of association between SpAs and ADs. Accordingly, SpAs might correspond more to autoinflammatory diseases rather than to ADs.
22014982 Iatrogenic immunosuppression and cutaneous malignancy. 2011 Nov Patients with autoimmune and inflammatory conditions often receive long-term immunosuppressive therapy. Some of the largest patient populations with iatrogenic immunosuppression include patients who have received solid-organ transplants or who have rheumatoid arthritis or psoriasis. Although treatments improve patient outcomes, individuals with immunosuppression subsequently may have an increased risk of skin cancer, including squamous cell carcinoma, basal cell carcinoma, and malignant melanoma.
22012554 Platelets in atherosclerosis. 2011 Nov Beyond obvious functions in haemostasis and thrombosis, platelets are considered to be essential in proinflammatory surroundings such as atherosclerosis, allergy, rheumatoid arthritis and even cancer. In atherosclerosis, platelets facilitate the recruitment of inflammatory cells towards the lesion sites and release a plethora of inflammatory mediators, thereby enriching and boosting the inflammatory milieu. Platelets do so by interacting with endothelial cells, circulating leukocytes (monocytes, neutrophils, dendritic cells, T-cells) and progenitor cells. This cross-talk enforces leukocyte activation, adhesion and transmigration. Furthermore, platelets are known to function in innate host defense through the release of antimicrobial peptides and the expression of pattern recognition receptors. In severe sepsis, platelets are able to trigger the formation of neutrophil extracellular traps (NETs), which bind and clear pathogens. The present antiplatelet therapies that target key pathways of platelet activation and aggregation therefore hold the potential to modulate platelet-derived immune functions by reducing cellular interactions of platelets with other immune components and by reducing the secretion of inflammatory proteins into the milieu. The objective of this review is to update and discuss the current perceptions of the platelet immune constituents and their prospect as therapeutic targets in an atherosclerotic setting.
21990059 [Generalized osteoarthritis in a young adult with type II collagenopathy]. 2011 Oct HISTORY AND ADMISSION FINDINGS: In the 20-year-old patient increasing arthralgia since the age of seven years had caused functional impairment. As seronegative osteodestructive rheumatoid arthritis had been suspected, he was treated with methotrexate and steorid for ovemore than one year, without success.r INVESTIGATIONS: The clinical examination revealed a compromised function of the knee and hip joints. Conventional radiographs showed severe degenerative changes in these regions. The radiographs of the lumbar and the thoracic spine were suggestive of osteoporotic fractures. DIAGNOSIS, TREATMENT AND COURSE: The clinical and radiological findings led to the suspicion of a hereditary collagenous disease. Genetic analyses revealed a COL2A1 mutation. The treatment included analgesics, non-steroidal antirheumatic drugs, opiates and regular physiotherapy to build up and maintain muscle strength. CONCLUSION: In young adult patients with osteoarthritis mutations in the COL2A1 gene should considered. This mutation with the substitution pArg75Cys should be in focus because of the phenotypes in clinical manifestations.
21808287 What's new in our understanding of the role of adipokines in rheumatic diseases? 2011 Aug 2 Important advances in our understanding of the relationships between adipokines, inflammation and the immune response have been achieved in the past 10 years. White adipose tissue has emerged as a highly dynamic organ that releases a plethora of immune and inflammatory mediators that are involved in numerous diseases, including not only rheumatic diseases such as rheumatoid arthritis, osteoarthritis and systemic lupus erythematosus, but also cardiovascular and metabolic complications that are frequently observed in rheumatic diseases. Our rapidly growing knowledge of adipokine biology is revealing the complexity of these amazing proteins, thereby redefining white adipose tissue as a key element of the inflammatory and immune response in rheumatic diseases. Adipokines exert potent modulatory actions on target tissues and cells involved in rheumatic disease, including cartilage, synovium, bone and various immune cells. In this Review, we describe the most recent advances in adipokine research in the context of rheumatic diseases, focusing primarily on leptin, adiponectin, visfatin and resistin, and also the potential role of newly identified adipokines such as chemerin, lipocalin 2 and serum amyloid A3.
21560455 [Lymphoproliferative disease in patients with autoimmune and inflammatory diseases: signif 2011 Evidence has been growing that the pathogenesis of lymphoproliferative disease involves immune processes deregulation. It is believed that antigens or immunological elements can trigger transformation of normal lymphocyte polyclonal population into monoclonal neoplastic disorder--lymphoproliferative disease. Extensive studies point to the link between malignant lymphoma development and autoimmune or inflammatory diseases--namely rheumatoid arthritis, Sjörgen's syndrome, coeliac disease, systemic lupus erythematosus or thyroiditis. Increased risk of lymphoproliferative disease development was also proved for some infections. These infections involve both viral (e.g. Epstein-Barr virus, HIV or hepatitis C virus) and bacterial agents (e.g. Helicobacter pylori, Borrelia burgdorferi). Besides various lymphomas, the links to autoimmune/inflammatory diseases have also been described in chronic lymphocytic leukaemia. Regarding clinical medicine, it is necessary to distinguish patients with autoimmune, inflammatory and infectious diseases who are at the increased risk of tumour development. New approaches must be found to lower this risk. Also, the relationship between autoimmune/inflammatory disease therapy and lymphoma development should be clarified. Although lymphomas associated with autoimmune and inflammatory diseases represent only a small proportion of all lymphomas, any new findings regarding these diseases can cast light on lymphoma pathogenesis as a whole.
21441609 IL-17-expressing cells as a potential therapeutic target for treatment of immunological di 2011 IL-17 is a multifunctional cytokine produced by activated CD4+ and CD8+ lymphocytes as well as stimulated unconventional Tγδ and natural killer T cells. IL-17 induces expression of chemokines, proinflammatory cytokines and metalloproteinases, thereby stimulating the inflammation and chemotaxis of neutrophils. Elevation of proinflammatory cytokines is associated with asthma and autoimmune disorders, such as multiple sclerosis, rheumatoid arthritis and psoriasis. Although the role of IL-17 in these disorders is not always easy to define, extensive research has demonstrated an aggravating influence of IL-17 in some animal models. Thus, the development of therapeutics to reduce IL-17 levels is a promising strategy for ameliorating inflammatory diseases. This review briefly summarizes recent knowledge about stimulants and intracellular signaling pathways that induce development and maturation of IL-17-expressing cells. Its positive and negative roles on disease progression and its importance in vaccine-induced memory are also discussed. Finally, recent literature describing potential therapeutic approaches for targeting IL-17 is presented.
21359919 Acupuncture for pain: an overview of Cochrane reviews. 2011 Mar OBJECTIVE: Cochrane reviews have the reputation for being more transparent and rigorous than other reviews. The aim of this overview was to evaluate and summarize Cochrane reviews of acupuncture for the treatment of any type of pain. METHODS: We searched the Cochrane Database and evaluated the Cochrane reviews that were concerned specifically with the effectiveness of acupuncture for pain. Data were extracted according to pre-defined inclusion criteria by two independent reviewers. RESULTS: Eight Cochrane reviews were included. They were all of high methodological quality. They related to a wide range of pain syndromes. Four reviews concluded that acupuncture is effective for migraines, neck disorders, tension-type headaches, and peripheral joint osteoarthritis; one review failed to demonstrate type the effectiveness of acupuncture for rheumatoid arthritis; and three reviews were inconclusive for shoulder pain, lateral elbow pain, and low back pain. CONCLUSION: Several Cochrane reviews of acupuncture for a wide range of pain conditions have recently been published. All of these reviews were of high quality. Their results suggest that acupuncture is effective for some but not all types of pain.
21253756 Tumor necrosis factor-alpha as a potential therapeutic target in idiopathic inflammatory m 2011 Jun The cytokine, tumor necrosis factor alpha (TNFα), has been implicated in many aspects of immune system development, immune response regulation, and T cell-mediated tissue injury. TNFα plays a less well-defined role in the pathogenesis of the idiopathic inflammatory myopathy (IIM) group of disorders, and has been considered a potential therapeutic target. Observational studies of TNFα-blockade in (mostly refractory) IIM have yielded inconsistent beneficial results so that administration of these biological agents is presently deemed an unreliable alternative treatment strategy. Moreover, anti-TNFα therapy has the rare potential to trigger myositis in patients with rheumatoid arthritis, hinting at a pre-existing "overlap disorder". The full potential of TNFα-antagonism will be realized only if randomized controlled trials ascertain appropriate treatment regimens and identify patient subgroups most likely to benefit from such therapy.
22754058 Folk medicinal uses of Verbenaceae family plants in Bangladesh. 2011 Folk medicinal practitioners form the first tier of primary health-care providers to most of the rural population of Bangladesh. They are known locally as Kavirajes and rely almost solely on oral or topical administration of whole plants or plant parts for treatment of various ailments. Also about 2% of the total population of Bangladesh are scattered among more than twenty tribes residing within the country's borders. The various tribes have their own tribal practitioners, who use medicinal plants for treatment of diseases. The objective of the present survey was to conduct an ethnomedicinal survey among the Kavirajes and tribal practitioners to determine which species of plants belonging to the Verbenaceae family are used by the practitioners. The Verbenaceae family plants are well known for constituents having important bio-active properties. The present survey indicated that 13 species belonging to 8 genera are used by the folk and tribal medicinal practitioners of Bangladesh. A comparison of their folk medicinal uses along with published reports in the scientific literature suggests that the Verbenaceae family plants used in Bangladesh can potentially be important sources of lead compounds or novel drugs for treatment of difficult to cure debilitating diseases like malaria and rheumatoid arthritis.
22700349 Morning granulocytopenia in two patients with connective-tissue disease treated with oral 2011 Mar 29 The authors report two cases of morning granulocytopenia: a 73-year-old female with a long-standing, active rheumatoid arthritis (RA) and a non-tuberculous mycobacteria (Mycobacterium avium) pulmonary infection, and a 55-year-old female with longstanding systemic lupus erythematosus (SLE). After admission, the patients' peripheral neutrophil counts decreased with no associated symptoms. In both cases, The authors identified diurnal variation in peripheral blood neutrophil counts in blood samples collected at 3-h intervals. The white cell count (WCC) in the first case rose from 2500 cells/μl (neutrophils: 1512 cells/μl) at 08:00 to 6100 cells/μl (neutrophils: 5185 cells/μl) at 14:00, and from 2200 cells/μl (neutrophils: 319 cells/μl) at 06:00 to 2900 cells/μl (neutrophils: 2291 cells/μl) at 12:00 in the second case. These cases are educational because necessary treatments would be stopped when morning granulocytopenia is not recognised. Morning granulocytopenia should be noted in the differential diagnosis in cases of incidentally found, asymptomatic granulocytopenia.
20737185 Successful treatment of steroid-resistant methotrexate-induced interstitial pneumonia with 2011 Feb A 76-year-old woman with rheumatoid arthritis who had been taking methotrexate (MTX) for 9 months was admitted because of acute respiratory failure. A chest radiograph revealed diffuse ground-glass attenuation. MTX-induced interstitial pneumonia (IP) was strongly suspected. Her respiratory failure worsened in spite of steroid pulse therapy. Intravenous administration of ulinastatin, however, dramatically improved her clinical condition. The second ulinastatin treatment was also effective. This case suggests that peripherally administered ulinastatin may be effective for steroid-resistant MTX-induced IP.
22916639 [Factors associated with gestational hypertension and preeclampsia]. 2012 Jul BACKGROUND: Hypertensive complications in pregnancy are a cause of morbidity and mortality. Previous studies have identified similarities and differences in risk factors of hypertensive complications during pregnancy. OBJECTIVE: Determine factors associated with gestational hypertension (HTG) and those related to preeclampsia (PEE). PATIENTS AND METHODS: Case-control study. We included women who completed pregnancy without complications (n=260) and were diagnosed with HTG (n=65) and PEE (n=65). We excluded patients with gestational or pre-pregnancy diabetes, thyroid disease (hypo and hyperthyroidism), autoimmune diseases (lupus erythematosus, rheumatoid arthritis) or diagnosed with heart disease or neuropathy before pregnancy. RESULTS: There were similarities in the risk factors such as: age over 35 years (OR 8.8, 95% CI 2.91-22.40), previous HTG (OR 64.16 95% CI 13.04-315.57) in case of patients with PEE. But we found a difference in the magnitude of these associations as odds ratios (OR) estimates were higher than in patients with HTG, age over 35 years (OR 3.33, 95% CI 1.03-10.72), and previous HTG (OR 27.27 95% CI 5.60-132.87). First-time pregnant women showed similar associations (OR 3.11 95% CI 1.52-6.38) in case of PEE or HTG (OR 3.14 95% CI 1.65-5.97). CONCLUSION: There are similarities in risk factors: maternal age--35 years, previous gestational hypertension and first-time pregnancy, for the development of gestational hypertension and preeclampsia.
23183379 Stem cells in autoimmune diseases: Implications for pathogenesis and future trends in ther 2013 May In this review we report the recent progresses, available in the literature, concerning the biology and the potential therapeutic role of both mesenchymal stem cells (MSCs) and hematopoietic stem cells in autoimmune diseases. Mesenchymal stem cells (MSCs) are responsible for the normal turnover and maintenance of adult mesenchymal tissues and their pleiotropic nature allows them to sense and respond to an event in the local environment, be it injury or inflammation. Recently, MSCs have been shown to have immune-modulatory properties and immunosuppressive capacities, acting on different immune cells both in vitro and in vivo, in addition to an immunologically privileged phenotype. Moreover, several works suggest that MSCs are defective in autoimmune diseases. These aspects are now considered the most intriguing aspect of their biology, introducing the possibility that these cells might be used as effective therapy in autoimmune diseases. Autoimmune diseases represent a failure of normal immune regulatory processes as they are characterized by activation and expansion of immune cell subsets in response to non-pathogenic stimuli. As autoimmune diseases can be transferred, or alternatively, cured, by stem cell transplantation, a defect in the hemopoietic stem cell as a cause of autoimmune diseases may be postulated. The rationale for autologous hematopoietic stem cell transplantation (HSCT) in autoimmune diseases is the ablation of an aberrant or self-reactive immune system by chemotherapy and regeneration of a new and hopefully self-tolerant immune system from hematopoietic stem cells. In the past 15years, more than 1500 patients worldwide have received HSCT, mostly autologous, as treatment for a severe autoimmune disease and the majority were affected by multiple sclerosis, systemic sclerosis, systemic lupus erythematosus, rheumatoid arthritis, juvenile idiopathic arthritis and idiopathic cytopenic purpura.
23076337 Meta-analysis reveals an association of PTPN22 C1858T with autoimmune diseases, which depe 2012 Dec Protein tyrosine phosphatase non-receptor type 22 (PTPN22) is a strong susceptibility gene shared by many autoimmune diseases. The aim of this study was to explore the mechanisms underlying this relationship. We performed a comprehensive analysis of the association between PTPN22 polymorphism C1858T and autoimmune diseases. The results showed a remarkable pattern; PTPN22 C1858T was strongly associated with type I diabetes, rheumatoid arthritis, immune thrombocytopenia, generalized vitiligo with concomitant autoimmune diseases, idiopathic inflammatory myopathies, Graves' disease, juvenile idiopathic arthritis, myasthenia gravis, systemic lupus erythematosus, anti-neutrophil cytoplasmic antibody-associated vasculitis and Addison's disease. By contrast, PTPN22 C1858T showed a negligible association with systemic sclerosis, celiac disease, multiple sclerosis, psoriasis, ankylosing spondylitis, pemphigus vulgaris, ulcerative colitis, primary sclerosing cholangitis, primary biliary cirrhosis, Crohn's disease and acute anterior uveitis. Further analysis revealed a clear distinction between the two groups of diseases with regard to their targeted tissues: most autoimmune diseases showing an insignificant association with PTPN22 C1858T manifest in skin, the gastrointestinal tract or in immune privileged sites. These results showed that the association of PTPN22 polymorphism with autoimmune diseases depends on the localization of the affected tissue, suggesting a role of targeted organ variation in the disease manifestations.
22840678 Casebook consults: improving outcomes in gout (multimedia activity). 2012 Aug Gout is a chronic, potentially debilitating condition characterized by an inflammatory process in the joints or periarticular tissues that results from the deposition of monosodium urate crystals. Underdiagnosis and undertreatment can lead to the development of tophi and chronic arthropathy. A presumptive diagnosis of gout can be made on the basis of the clinical presentation as well as risk factors such as metabolic syndrome. Key conditions to rule out in the differential diagnosis are septic arthritis, calcium pyrophosphate deposition disease (pseudogout), fracture, and rheumatoid arthritis. Acute flares of gout should be managed with nonsteroidal antiinflammatory drugs (NSAIDs), colchicine, or corticosteroids. With a diagnosis of gout, if urate-lowering therapy (ULT) is required, prophylaxis should be considered with low-dose colchicine or an NSAID, followed by the addition of ULT. The goal of ULT is to reach a serum uric acid (SUA) level ≤6.0 mg/dL. Measurements of SUA should be obtained after resolution of an acute attack, then periodically to facilitate titration of the ULT dose to achieve the target SUA level. Studies have confirmed significant reductions in gout attacks among patients who have attained SUA levels ≤6.0 mg/dL with ULT. Patient education concerning the disease and its treatment is essential to ensure close adherence with recommended therapies. Patients should also understand that ULT is intended as long-term, and for most patients, lifelong therapy to maximize the prospects for control of the disease. Clinicians should feel confident in making a presumptive diagnosis and choosing a therapeutic regimen for gout while effectively communicating with and educating patients about their disease.
22771631 N-O-isopropyl sulfonamido-based hydroxamates: kinetic characterisation of a series of MMP- 2012 Sep 15 Matrix metalloproteinases (MMPs) are a family of zinc dependent endopeptidases known to play key roles in extracellular matrix (ECM) breakdown disorders, such as the two main forms of arthritis, rheumatoid arthritis (RA) and osteoarthritis (OA). MMP-13 (collagenase 3) is the leading MMP involved in cartilage degradation through its particular ability to cleave type-II collagen and as such plays a pivotal role in the pathogenesis of these diseases. Here we report the kinetic characterisation of N-O-isopropyl sulfonamido-based hydroxamates, potent inhibitors of MMP-13 and MMP-12, bearing different P1 and P1' substituents. One of these compounds proved to be a potent (4 ≤ K(i) ≤ 5 nM) slow-binding inhibitor towards MMP-13 and MMP-12, with very favourable low association (10(4) M(-1) s(-1)) and dissociation constants (10(-4) s(-1)). Moreover, this compound exhibited a good selectivity for MMP-13 and MMP-12 over MMP-1, MMP-3, MMP-7, MMP-8 and, even to a minor extent, MMP-2. A molecular-docking study carried out using the experimentally-derived X-ray crystal structure of MMP-12 (PDB ID: 3F17) revealed critical hydrogen bonding of the hydroxamate and the sulfonamide moieties with key active site residues. Since also MMP-12 is involved in RA, this MMP-13/MMP-12 dual target inhibitor could be a valid candidate for the treatment of this pathology.
22721447 Visualizing arthritic inflammation and therapeutic response by fluorine-19 magnetic resona 2012 Jun 21 BACKGROUND: Non-invasive imaging of inflammation to measure the progression of autoimmune diseases, such as rheumatoid arthritis (RA), and to monitor responses to therapy is critically needed. V-Sense, a perfluorocarbon (PFC) contrast agent that preferentially labels inflammatory cells, which are then recruited out of systemic circulation to sites of inflammation, enables detection by 19F MRI. With no 19F background in the host, detection is highly-specific and can act as a proxy biomarker of the degree of inflammation present. METHODS: Collagen-induced arthritis in rats, a model with many similarities to human RA, was used to study the ability of the PFC contrast agent to reveal the accumulation of inflammation over time using 19F MRI. Disease progression in the rat hind limbs was monitored by caliper measurements and 19F MRI on days 15, 22 and 29, including the height of clinically symptomatic disease. Naïve rats served as controls. The capacity of the PFC contrast agent and 19F MRI to assess the effectiveness of therapy was studied in a cohort of rats administered oral prednisolone on days 14 to 28. RESULTS: Quantification of 19F signal measured by MRI in affected limbs was linearly correlated with disease severity. In animals with progressive disease, increases in 19F signal reflected the ongoing recruitment of inflammatory cells to the site, while no increase in 19F signal was observed in animals receiving treatment which resulted in clinical resolution of disease. CONCLUSION: These results indicate that 19F MRI may be used to quantitatively and qualitatively evaluate longitudinal responses to a therapeutic regimen, while additionally revealing the recruitment of monocytic cells involved in the inflammatory process to the anatomical site. This study may support the use of 19F MRI to clinically quantify and monitor the severity of inflammation, and to assess the effectiveness of treatments in RA and other diseases with an inflammatory component.
22579684 Osmolarity regulates chondrogenic differentiation potential of synovial fluid derived mese 2012 Jun 8 Cartilage is one of few tissues where adult stem/progenitor cells have not been putatively identified. Recent studies have provided strong evidence that a sub-population of mesenchymal progenitor cells (MPCs) derived from the synovial fluid may be able to affect some degree of cartilage repair both in vivo and in vitro/ex vivo, however this does not appear to be the case in patients with arthritis. Previously, it has been found that synovial fluid osmolarity is decreased in patients with osteoarthritis (OA) or Rheumatoid arthritis (RA) and these changes in osmolarity have been linked to changes in chondrocyte gene regulation. However, it is yet unknown if changes in osmolarity regulate the gene expression in synovial fluid MPCs (sfMPCs), and by extension, chondrogenesis of this cell population. In the present study we have collected synovial fluid samples from normal, OA and RA knee joints, quantified the osmolarity of the fluid and modified the culture/differentiation media to span a range of osmolarities (264-375 mOsm). Chondrogenesis was measured with Alcian blue staining of cultures in addition to quantitative PCR (qPCR) using probes to Sox9, ACAN and Col2A1. Overall, sfMPCs from arthritic joints demonstrated decreased chondrogenic potential compared to sfMPCs isolated from normal synovial fluid. Furthermore, the sfMPCs retained increased chondrogenic potential if differentiated under the same osmolarity conditions for which they were initially derived within. In conclusion, it does appear the synovial fluid osmolarity regulates the chondrogenic potential of sfMPCs, however, further study is required to elucidate the mechanism by which the changes in osmolarity are sensed by the cells and regulate chondrogenic gene expression.
22228237 The practical value of biologics registries in Africa and Middle East: challenges and oppo 2012 Mar Biologics, including tumor necrosis factor (TNF) inhibitors, are increasingly used for the treatment of inflammatory conditions such as rheumatoid arthritis (RA), psoriatic arthritis, and ankylosing spondylitis. The efficacy of these drugs has been demonstrated in randomized controlled trials (RCTs). However, these studies are conducted in controlled environments, and the results may not necessarily reflect clinical outcomes in daily clinical practice. In Europe and other western countries, numerous biologics registries that enroll and monitor patients receiving biologics have been established. These registries follow patients irrespective of whether they continue with the initial biologic drug. Thus, real-life efficacy data from these registries can be used to assess the long-term safety of biologics through longitudinal studies. In Africa and Middle East (AFME), such registries currently exist only in Morocco and South Africa. In light of the increasing availability of biologics and scarcity of long-term safety data of these agents in the AFME population, there is a need to establish biologics registries in other countries across the region. This review discusses the value of biologics registries versus RCTs as well as safety and efficacy data from observational studies presented as lessons from well-established biologics registries. In addition, the rationale for establishing such registries in the AFME region is also presented.