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ID PMID Title PublicationDate abstract
22784556 Pathogenic features of CD4+CD28- T cells in immune disorders. 2012 Aug Aging of the immune system contributes to the increased morbidity and mortality of the elderly population and may occur prematurely in patients with immune disorders. One of the main characteristics of immunosenescence is the expansion of CD4(+)CD28(-) T cells in the blood. These cells are effector memory T cells with cytotoxic capacity, and have been recently described to have pathogenic potential in a variety of immune disorders. Interestingly, CD4(+)CD28(-) T cells have now been found to infiltrate target tissues of patients with multiple sclerosis, rheumatoid arthritis, myopathies, acute coronary syndromes, and other immune-related diseases. In this review, we discuss potential factors and mechanisms that may induce the expansion of these cells, as well as their putative pathogenic mechanisms in immune disorders.
22632278 Patient instructors in rheumatology. 2012 Patient instructors are patients trained to teach students in focussed history taking and/or examination in the context of the patient's specific illness. Their espousal has been quite extensively reported in rheumatology. The majority of studies show that patient instructors are effective in enhancing the knowledge and skills relevant to practice concerned with patients with the given conditions (in this case, typically rheumatoid arthritis and osteoarthritis). Most studies show patient instructors to be as effective as clinicians in this respect. They are especially effective at enhancing students' understanding of the impact of living with a chronic condition. With appropriate (quite extensive) training, they can also assess the examination skills of students, both undergraduate and postgraduate. Students value them, and the patient instructors themselves derive benefit from the activity. There are issues to be aware of regarding the adoption of patient instructors. The training required is significant. If employed as described in the literature, quite significant selection criteria come into play. In some cases, patient instructors feel under-rewarded financially; they should not be seen as medical education on the cheap. Nonetheless, patient instructors represent an excellent, relatively under-utilised, resource for the aiding of student learning in many areas of medicine.
22338301 The clinical-diagnostic role of antistreptolysin O antibodies. 2011 Nov The antistreptolysin O antibody (ASLO) test is often requested in a clinical setting with limited evidence for its usefulness. For this reason, the diagnostic scenario in which ASLO plays an evidence-based role and the analytical performance of the test are critically appraised, taking into account the clinical need and the direct medical cost. Little or no scientific evidence was found for the use of ASLO in patients with pharyngitis, post-streptococcal glomerulonephritis and in adults with rheumatoid arthritis. The clinical relevance of ASLO is restricted to paediatrics, where it contributes to fulfil the diagnosis of acute rheumatic fever (ARF) as per Jones criteria. The standardization of current automated ASLO-latex assays is limited. Attention should be paid to inaccurate reference values and many circumstances causing false positive and false negative results. Because of a low prevalence of ARF in the Western world, a high negative predictive value is obtained for the ASLO test (> 99%). In clinical practice, the result of the test is not urgent. To reduce overconsumption, the clinical laboratory should drive the request behaviour of physicians by a strategic lay-out of the application form. The health insurance/government also contributed by introducing a diagnostic rule for reimbursement.
22214804 [microRNA in autoimmune disorders]. 2011 microRNAs, short ribonucleic acid molecules which is typically 20-25 nucleotides long, can bind to complementary sequences in the three prime untranslated regions of target mRNAs, leading to the inhibition of translation or degradation of the mRNA. Theologically, human genome may have more than 1000 microRNAs, which target about 60% of human mRNAs. Thus, microRNAs have been implicated in the pathogenesis of various disorders. This paper discusses the present day understanding about the expression and role in various autoimmune diseases including rheumatoid arthritis, Sjogren syndrome, polymyositis/dermatomyositis, systemic lupus erythematosus, scleroderma, type I diabetis, and psoriasis. For example, the expression of miR-29, which targets type I collagen mRNA, is reported to be down-regulated in cultured dermal fibroblasts derived from scleroderma skin, contributing to excessive collagen production in this disease. Supplementation of the microRNA results in the decrease of collagen expression in scleroderma fibroblasts. In addition, serum miR-29a levels are significantly decreased in the very early stage of scleroderma. Investigation of the involvement of microRNAs in the pathogenesis of each autoimmune disease may lead to develop new biomarker and new therapeutic approach.
23951473 Cross-talk between T cells and osteoclasts in bone resorption. 2012 Osteoclasts (OCs) are the exclusive bone resorptive cell, they derive from monocyte/macrophage precursors, which can circulate within the hematopoietic cell pool or be resident in a number of tissues. The maintenance of an adequate bone mass depends on the controlled and timely removal of old, damaged bone. The increase of OC activity is observed in many pathologies characterised by bone loss, such as osteoporosis, rheumatoid arthritis, bone metastasis, periprosthetic osteolysis in aseptic loosening of arthroplasty and also in pediatric diseases, such as phenilketonuria and 21-hydroxylase deficiency. During the bone resorption process there is an intense cross-talk between immune system cells and OCs. In particular, T cells release factors and cytokines, which rule osteoclastogenesis, and on the other hand, OCs produce factors that act on T cells. A primary mediator of osteoclastogenesis is the receptor activator of nuclear factor-κβ-RANK ligand-osteoprotegerin system, but also other cytokines promote OC activation according to the different pathologies. This review summarizes the main mechanisms promoting osteoclastogenesis in diseases characterised by bone loss, focusing on factors and cytokines involved in this process and on the interaction between OCs and T cells.
21904885 Vasculitides throughout history and their clinical treatment today. 2011 Dec Therapeutic management of the vasculitides is closely linked to modern rheumatologic advances, particularly as it relates to the discovery and first clinical use of glucocorticoids. These compounds were introduced in the late-1940s for the treatment of rheumatoid arthritis, but soon after, clinicians in Europe and the United States realized that they could have a significant positive impact in systemic vasculitides. However, once it was realized that glucocorticoid use was associated with a high degree of morbidity, the search for better immunosuppressive agents with similar efficacy but improved safety profiles was on. During the past several years, several agents have been utilized for the therapeutic management of systemic vasculitides, and the list keeps growing with the development of newer compounds that have retained efficacy but with a better safety profile.
21637066 FDG PET/CT in a patient with spontaneous remission of methotrexate-associated lymphoprolif 2011 Jul We report a case that fluorodeoxyglucose positron emission tomography (FDG PET)/computed tomography (CT) depicted systemically multiple lesions of methotrexate (MTX)-associated lymphoproliferative disorders. A 70-year-old man receiving MTX for rheumatoid arthritis complained of neck swelling. FDG PET/CT revealed multiple FDG-avid lesions in lymph nodes, lungs, bones, and muscles. Lesions in bones and muscles were not detected on X-CT. Final diagnosis of cervical node was confirmed as MTX-associated lymphoproliferative disorders. FDG PET/CT performed 148 days after discontinuing MTX demonstrated complete remission.
21553073 [Managing comorbidities of inflammatory rheumatic diseases]. 2011 Jun Patients with inflammatory rheumatic diseases often suffer from considerable comorbidities that can arise due to the chronic systemic inflammatory activity of the rheumatic disease itself, disorders of immune defense, or as a result of antirheumatic treatment; they can also occur independently. For example, almost 50% of patients with rheumatoid arthritis already exhibit two further chronic diseases at the time of initial manifestation. With regard to the elevated mortality observed in patients with rheumatism, particularly cardiovascular morbidity and increased predisposition to infections are of note. In addition, this article addresses further important possible concomitant diseases, i.e., osteoporosis and tumor diseases. A ground rule is to identify comorbidities and treat them just as diligently as the underlying rheumatic disease so that the patient with rheumatism should be accompanied by an interdisciplinary team of internists during each phase of the disease. Effective control of the systemic inflammatory activity may serve to reduce the risk of certain cardiovascular and neoplastic comorbidities.
21441817 Rituximab in the treatment of bullous systemic lupus erythematosus. 2011 Apr Rituximab is a CD20 chimeric monoclonal antibody. It was approved by the US Food and Drug Administration for the treatment of relapsed or refractory low-grade or follicular non-Hodgkin lymphoma and for the treatment of moderate to severely active rheumatoid arthritis. It has been used as an off-label treatment in many autoimmune diseases, where B cells play a major role in the pathogenesis. We report a case of successful use of rituximab in the treatment of refractory bullous systemic lupus erythematosus in an African American patient.
29319976 2011 Feb It is estimated that 20,000-30,000 people in Norway suffer from the disease. Due to the patients’ reduced functional capacity, costs are incurred by employers, relatives and not least the patients themselves. Research has shown that early treatment with biologic drugs may be beneficial. Biologics are however more costly than conventional DMARDs, and Norwegian guidelines therefore stipulate that at least one DMARD should be attempted before treatment with biologic drugs is initiated. The Norwegian Knowledge Centre for the Health Services has reviewed the literature on the cost-effectiveness of biologic treatment for early RA as part of a project commissioned by the commissioned by the Norwegian Rheumatism Association. We searched systematically for health economic evaluations of biologic treatment of patients with early RA (disease duration of three years or less) compared with DMARD treatment. We found six studies, which all incorporated a TNF-inhibitor such as aldalimumab, etanercept or infliximab. No studies on the other biologic drugs were found. Our findings were: Treatment with biologic drugs in early RA may be cost-effective, though not necessarily as first-line treatment. This is consistent with current Norwegian guidelines which state that treatment with at least one DMARD should be attempted before biologic treatment is initiated. Inclusion of indirect costs has a major bearing on the results. The study results vary significantly.
21188427 Upper airway obstruction associated with flexed cervical position after posterior occipito 2011 Feb Upper airway obstruction resulting from overflexion fixation of the cervical spine is a rare but life-threatening complication after cervical spine surgery. There are few reports of dyspnea after a posterior cervical fusion. We present the case of a 63-year-old woman with rheumatoid arthritis who developed an upper airway obstruction immediately after an O-C4 fusion. She was reintubated with a fiberoptic scope. Revision surgery allowing the angle to return to the neutral position was performed to ameliorate the overflexion of the cervical spine fixation and the consequent upper airway obstruction. After revision surgery, the upper airway obstruction disappeared. Our experience suggests that intraoperative use of fluoroscopy and extubation with a tube exchanger are recommended to avoid this complication, especially in patients at high risk of upper airway obstruction.
30742401 Piroxicam Therapy and CYP2C9 Genotype. 2012 Piroxicam (brand name Feldene) is a nonsteroidal anti-inflammatory drug (NSAID) used to treat osteoarthritis and rheumatoid arthritis. Piroxicam provides pain relief and reduces inflammation. Piroxicam is primarily metabolized by CYP2C9. Individuals who lack CYP2C9 activity (“CYP2C9 poor metabolizers”) have an increased exposure to piroxicam, and an increased risk of side effects. Like all NSAIDs, piroxicam increases the risk of serious cardiovascular events, including myocardial infarction and stroke, and serious gastrointestinal (GI) adverse events such as bleeding, ulceration, and perforation. The standard dose of piroxicam for osteoarthritis and rheumatoid arthritis in adults is 20 mg once daily. But for all patients, the lowest effective dose of piroxicam should be used for the shortest length of time, consistent with the treatment goals of each individual (1). The FDA-approved drug label for piroxicam states that a dose reduction should be considered in “patients who are known or suspected to be poor CYP2C9 metabolizers based on genotype or previous history/experience with other CYP2C9 substrates (such as warfarin and phenytoin)”. Dose reductions should be considered because these patients may have abnormally high plasma levels of piroxicam caused by reduced metabolic clearance. However, specific dose reductions based on CYP2C9 phenotype are not provided (Table 1) (1). As for all NSAIDs, piroxicam is contraindicated in patients with a known hypersensitivity, a history of asthma, urticaria, or other allergic-type reactions after taking aspirin or another NSAID, and following coronary artery bypass graft (CABG) surgery. Piroxicam should also be avoided by pregnant women starting at 30 weeks gestation.
22387094 Arctigenin suppresses receptor activator of nuclear factor κB ligand (RANKL)-mediated ost 2012 May 5 Osteoclasts, multinucleated bone-resorbing cells, are closely associated with bone diseases such as rheumatoid arthritis and osteoporosis. Osteoclasts are derived from hematopoietic precursor cells, and their differentiation is mediated by two cytokines, including macrophage colony stimulating factor and receptor activator of nuclear factor κB ligand (RANKL). Previous studies have shown that arctigenin exhibits an anti-inflammatory effect. However, the effect of arctigenin on osteoclast differentiation is yet to be elucidated. In this study, we found that arctigenin inhibited RANKL-mediated osteoclast differentiation in bone marrow macrophages in a dose-dependent manner and suppressed RANKL-mediated bone resorption. Additionally, the expression of typical marker proteins, such as NFATc1, c-Fos, TRAF6, c-Src, and cathepsin K, were significantly inhibited. Arctigenin inhibited the phosphorylation of Erk1/2, but not p38 and JNK, in a dose-dependent manner. Arctigenin also dramatically suppressed immunoreceptor tyrosine-based activation motif-mediated costimulatory signaling molecules, including Syk and PLCγ2, and Gab2. Notably, arctigenin inhibited the activation of Syk through RANKL stimulation. Furthermore, arctigenin prevented osteoclast differentiation in the calvarial bone of mice following stimulation with lipopolysaccharide. Our results show that arctigenin inhibits osteoclast differentiation in vitro and in vivo. Therefore, arctigenin may be useful for treating rheumatoid arthritis and osteoporosis.
22849293 Epigallocatechin-3-gallate modulates antioxidant and DNA repair-related proteins in exocri 2012 Nov The autoimmune disorder primary Sjogren's syndrome (SS) is associated with xerostomia and xerophthalmia. SS pathogenesis involves both genetic/epigenetic and environmental factors. A major potential contributor is oxidative stress associated with damage to cellular components, including DNA. We reported previously that the green tea polyphenol epigallocatechin-3-gallate (EGCG) normalizes the elevated levels of proliferating cell nuclear antigen (PCNA), a key component of DNA repair, in the NOD mouse model for SS and type 1 diabetes. The current study examined levels of the antioxidant enzymes peroxiredoxin 6 (PRDX6), catalase and superoxide dismutase (SOD), as well as PCNA, in NOD.B10.Sn-H2 mice, a model for primary SS, and determined the effect of EGCG on their expression. PCNA elevation was detected in the submandibular gland and pancreas by 8 weeks of age in water-fed mice, and increased through 14 weeks of age, prior to overt onset of symptoms. This early PCNA elevation was followed by a decline of peroxiredoxin 6 protein. In contrast, EGCG-fed mice exhibited normal levels of PCNA and peroxiredoxin 6, comparable to healthy untreated BALB/c mice. Similar patterns were observed in the pancreas, even though these mice do not develop diabetes. Thus, elevated PCNA is an early biomarker for exocrine glandular dysfunction associated with SS-like autoimmune disease, accompanied subsequently by decreased PRDX6 antioxidant enzyme levels that could further contribute to oxidative stress, and these changes precede inflammatory cell infiltration. Importantly, EGCG consumption normalizes the expression of these biomarkers in this model. These observations could lead to early diagnosis and intervention of autoimmune disorders.
21239502 Resveratrol-mediated SIRT-1 interactions with p300 modulate receptor activator of NF-kappa 2011 Apr 1 Resveratrol is a polyphenolic phytoestrogen that has been shown to exhibit potent anti-oxidant, anti-inflammatory, and anti-catabolic properties. Increased osteoclastic and decreased osteoblastic activities result in bone resorption and loss of bone mass. These changes have been implicated in pathological processes in rheumatoid arthritis and osteoporosis. Receptor activator of NF-κB ligand (RANKL), a member of the TNF superfamily, is a major mediator of bone loss. In this study, we investigated the effects of resveratrol on RANKL during bone morphogenesis in high density bone cultures in vitro. Untreated bone-derived cell cultures produced well organized bone-like structures with a bone-specific matrix. Treatment with RANKL induced formation of tartrate-resistant acid phosphatase-positive multinucleated cells that exhibited morphological features of osteoclasts. RANKL induced NF-κB activation, whereas pretreatment with resveratrol completely inhibited this activation and suppressed the activation of IκBα kinase and IκBα phosphorylation and degradation. RANKL up-regulated p300 (a histone acetyltransferase) expression, which, in turn, promoted acetylation of NF-κB. Resveratrol inhibited RANKL-induced acetylation and nuclear translocation of NF-κB in a time- and concentration-dependent manner. In addition, activation of Sirt-1 (a histone deacetylase) by resveratrol induced Sirt-1-p300 association in bone-derived and preosteoblastic cells, leading to deacetylation of RANKL-induced NF-κB, inhibition of NF-κB transcriptional activation, and osteoclastogenesis. Co-treatment with resveratrol activated the bone transcription factors Cbfa-1 and Sirt-1 and induced the formation of Sirt-1-Cbfa-1 complexes. Overall, these results demonstrate that resveratrol-activated Sirt-1 plays pivotal roles in regulating the balance between the osteoclastic versus osteoblastic activity result in bone formation in vitro thereby highlighting its therapeutic potential for treating osteoporosis and rheumatoid arthritis-related bone loss.
21805176 Rituximab treatment for Sjogren syndrome-associated non-Hodgkin's lymphoma: case series. 2012 Oct Five per cent of patients with primary Sjogren's syndrome (pSS) develop malignant non-Hodgkin's lymphoma (NHL), usually of the mucosa-associated lymphoid tissue (MALT) and most frequently located in the major salivary glands. Rituximab (RTX), a chimeric monoclonal antibody against the CD20 molecule expressed on the surface of mature B cells that has been approved for the treatment of NHL, has been used to treat pSS-associated lymphoma. We have described two cases: one with MALT lymphoma in the parotid glands and the other with a rare thymus lymphoma accompanied by the rare complication of a bullous pneumopathy. Both were treated with RTX at haematological doses, which was unsuccessful in the patient with a salivary lymphoma; in the case of the patient with a thymus lymphoma, the mediastinum mass disappeared and did not relapse. Both patients experienced an improvement in the subjective symptoms of dryness, and their Schirmer's test and scialoscintigraphy results stabilised. The pulmonary bullae remained unchanged.
21469088 Altered miR-146a expression in Sjögren's syndrome and its functional role in innate immun 2011 Jul MicroRNAs (miRNAs), small non-coding RNA molecules that post-transcriptionally regulate gene expression, are known to play key roles in regulating immune responses and autoimmunity. We investigated miR-146a expression in Sjögren's syndrome (SjS) patients as well as in the SjS-prone C57BL/6.NOD-Aec1Aec2 mouse model, to elucidate its involvement in SjS pathogenesis. Expression of miR-146a was examined in the PBMCs of 25 SjS patients and ten healthy donors, as well as in PBMCs, salivary and lacrimal glands of SjS-prone mice and WT C57BL/6J mice. Functional assays using THP-1 human monocytes were conducted to determine the biological roles of miR-146a in innate immunity. Expression of miR-146a was significantly increased in SjS patients compared with healthy controls, and was upregulated in the salivary glands and PBMCs of the SjS-prone mouse at both 8 wk (prior to disease onset) and 20 wk (full-blown disease) of age. More importantly, functional analysis revealed roles for miR-146a in increasing phagocytic activity and suppressing inflammatory cytokine production while migration, nitric oxide production and expression of antigen-presenting/costimulatory molecules are not affected in human monocytic THP-1 cells. Taken together, our data suggest that abnormal expression/regulation of microRNAs in innate immunity may contribute to, or be indicative of, the initiation and progression of SjS.
21427176 Novel carbonic anhydrase autoantibodies and renal manifestations in patients with primary 2011 Aug OBJECTIVE: Anti-carbonic anhydrase II (anti-CA II) antibodies have been related to renal manifestations of primary SS (pSS), and animal studies have even suggested a pathogenic role for them. However, not all pSS patients with renal tubular acidosis (RTA) present with anti-CA II antibodies. Recently, several novel CA isoenzymes have been recognized and we aimed to investigate whether antibodies to these are associated with renal manifestations of pSS. METHODS: We examined anti-CA II antibodies as well as anti-CA I, VI, VII and XIII antibodies by ELISA tests in 74 pSS patients on whom detailed nephrological examinations had been performed and, as controls, in 56 subjects with sicca symptoms, but no pSS. RESULTS: The levels of anti-CA I, II, VI and VII antibodies were significantly higher in patients with pSS compared with subjects with sicca symptoms but no pSS. None of the anti-CA antibodies was associated with the presence of complete or incomplete RTA or proteinuria or urinary α₁m excretion in patients with pSS. However, levels of anti-CA II, VI and XIII antibodies correlated significantly with urinary pH, and inversely with serum sodium concentrations. The degree of 24-h urinary protein excretion correlated weakly with levels of anti-CA VII antibodies. CONCLUSION: Not only antibodies to CA II, but also anti-CA VI and XIII antibodies seem to be associated with renal acidification capacity in patients with pSS.
21388871 Clinical manifestations in individuals with recent diagnosis of HTLV type I infection. 2011 May BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1) is known to cause HTLV-associated myelopathy (HAM)/tropical spastic paraparesis and adult T cell leukemia. A growing body of evidence links HTLV-1 infection with an increasing spectrum of disease, including uveitis, periodontal disease, arthropathy, sicca syndrome, and neurologic deficits. OBJECTIVES: Despite recent findings, the natural history of HTLV-1 infection remains poorly defined. This study was designed to better characterize initial clinical and neurological findings in individuals diagnosed with HTLV-1 infection. STUDY DESIGN: We conducted a cross-sectional study of 71 individuals recently diagnosed with HTLV-1 and 71 uninfected age- and sex-matched blood donors in Salvador, Brazil. Subjects were administered a standardized questionnaire and underwent physical exam. RESULTS: HTLV-1 infected subjects were significantly more likely than controls to report complaints of hand and foot numbness (OR=5.3; 95% CI: 1.8-15.3; p=0.002 and OR=4.0; 95% CI: 1.3-12; p=0.013 respectively), difficulty running (OR=4.0; 95% CI: 1.1-14.2; p=0.032), nocturia (OR=5.0; 95% CI: 1.1-22.8; p=0.038), arthralgia (OR=3.3; 95% CI: 1.4-7.7; p=0.006), and photophobia (OR=3.3; 95% CI: 1.4-7.7; p=0.006). CONCLUSIONS: Neurologic, ocular and rheumatologic complaints may be the first manifestations of HTLV-1 infection. Therefore, all patients presenting with initial diagnosis should be rigorously screened for these symptoms.
22132879 Translational Mini-Review Series on B cell subsets in disease. Transitional B cells in sys 2012 Jan Systemic lupus erythematosus (SLE) and Sjögren's syndrome are autoimmune disorders which are characterized by a disturbed B cell homeostasis which leads ultimately to dysfunction of various organs. One of the B cell subsets that appear in abnormal numbers is the population of transitional B cells, which is increased in the blood of patients with SLE and Sjögren's syndrome. Transitional B cells are newly formed B cells. In mice, transitional B cells undergo selection checks for unwanted specificity in the bone marrow and the spleen in order to eliminate autoreactive B cells from the circulating naive B cell population. In humans, the exact anatomical compartments and mechanisms of the specificity check-points for transitional B cells remain unclear, but appear to be defective in SLE and Sjögren's syndrome. This review aims to highlight the current understanding of transitional B cells and their defects in the two disorders before and after B cell-targeted therapies.