Browse

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

ID PMID Title PublicationDate abstract
26174031 TLR4 Asp299Gly polymorphism may be protective against chronic periodontitis. 2016 Apr BACKGROUND AND OBJECTIVE: Periodontitis results from interplay between genetic and environmental factors. Single nucleotide polymorphisms (SNPs) in the coding region of the toll-like receptor 4 gene (TLR4) may be associated with periodontitis, although previous studies have been inconclusive. Moreover, the interaction between environmental factors, such as cigarette smoking (a major risk factor for periodontitis), and Porphyromonas gingivalis (a major periodontal pathogen) with the TLR4 coding region Asp299Gly SNP (rs4986790; a SNP associated with lipopolysaccharide-mediated inflammatory responses in periodontitis), have been largely ignored in previous reports. Therefore, the objective of this study was to examine the association between TLR4 Asp299Gly (rs4986790) with alveolar bone height loss (ABHL) and periodontitis, accounting for interactions between this SNP with smoking and P. gingivalis prevalence. The CD14/-260 SNP (rs2569190) served as a control, as a recent meta-analysis suggested no relationship between this SNP and periodontitis. MATERIAL AND METHODS: This multicenter study included 617 participants who had rheumatoid arthritis or osteoarthritis. This report presents a secondary outcome from the primary case-control study examining the relationship of periodontitis with established rheumatoid arthritis. The Centers for Disease Control/American Academy of Periodontology case definitions of periodontitis were used for this analysis. Participants received a full-mouth clinical periodontal examination and panoramic radiograph. Percentage ABHL was measured on posterior teeth. The TLR4 Asp299Gly and CD14/-260 SNPs were selected a priori and genotypes were determined using the ImmunoChip array (Illumina(®) ). Minor allele frequencies and associations with periodontitis and ABHL did not differ according to rheumatoid arthritis vs. osteoarthritis status; therefore, data from these two groups were pooled. The presence of P. gingivalis was detected in subgingival plaque by PCR. Multivariate ordinal logistic regression examined associations between the SNPs and periodontitis or ABHL. SNP interactions with smoking and P. gingivalis were analyzed. RESULTS: A significant, negative interaction was observed between the TLR4 SNP and the presence of P. gingivalis (p = 0.045) with respect to periodontitis. The TLR4 minor variant was also associated with less ABHL: 16.8% of individuals with low ABHL, 9.0% with moderate ABHL and 11.2% with high ABHL had the minor allele [p = 0.029; odds ratio = 0.58 (95% confidence interval: 0.36-0.95)]. The interaction between the TLR4 SNP and smoking was not significant with respect to periodontitis or ABHL. The CD14 SNP was not associated with periodontitis or ABHL. CONCLUSION: The TLR4 Asp299Gly SNP significantly interacted with P. gingivalis in conferring a decreased risk of periodontitis and may be protective against ABHL, a feature of periodontitis. Agents blocking TLR4 signaling, a strategy currently under investigation for the treatment of other inflammatory conditions, may warrant investigation in the context of periodontitis related to the presence of P. gingivalis.
26972733 The wound/burn guidelines - 4: Guidelines for the management of skin ulcers associated wit 2016 Jul The Japanese Dermatological Association prepared guidelines focused on the treatment of skin ulcers associated with connective tissue disease/vasculitis practical in clinical settings of dermatological care. Skin ulcers associated with connective tissue diseases or vasculitis occur on the background of a wide variety of diseases including, typically, systemic sclerosis but also systemic lupus erythematosus (SLE), dermatomyositis, rheumatoid arthritis (RA), various vasculitides and antiphospholipid antibody syndrome (APS). Therefore, in preparing the present guidelines, we considered diagnostic/therapeutic approaches appropriate for each of these disorders to be necessary and developed algorithms and clinical questions for systemic sclerosis, SLE, dermatomyositis, RA, vasculitis and APS.
26113182 Saussurea involucrata: A review of the botany, phytochemistry and ethnopharmacology of a r 2015 Aug 22 ETHNOPHARMACOLOGICAL RELEVANCE: Saussurea involucrata Matsum. & Koidz. is an endangered species of the Asteraceae family, growing in the high mountains of central Asia. It has been, and is, widely used in traditional Uyghur, Mongolian and Kazakhstan medicine as well as in Traditional Chinese Medicine as Tianshan Snow Lotus (Chinese: ). In traditional medical theory, S. involucrata can promote blood circulation, thereby alleviating all symptoms associated with poor circulation. It also reputedly eliminates cold and dampness from the body, diminishes inflammation, invigorates, and strengthens Yin and Yang. It has long been used to treat rheumatoid arthritis, cough with cold, stomach ache, dysmenorrhea, and altitude sickness in Uyghur and Chinese medicine. AIM OF THE REVIEW: To comprehensively summarize the miscellaneous research that has been done regarding the botany, ethnopharmacology, phytochemistry, biological activity, and toxicology of S. involucrata. METHOD: An extensive review of the literature was carried out. Apart from different electronic databases including SciFinder, Chinese National Knowledge Infrastructure (CNKI), ScienceDirect that were sourced for information, abstracts, full-text articles and books written in English and Chinese, including those traditional records tracing back to the Qing Dynasty. Pharmacopoeia of China and other local herbal records in Uighur, Mongolian and Kazakhstan ethnomedicines were investigated and compared for pertinent information. RESULTS: The phytochemistry of S. involucrata has been comprehensively investigated. More than 70 compounds have been isolated and identified; they include phenylpropanoids, flavonoids, coumarins, lignans, sesquiterpenes, steroids, ceramides, polysaccharides. Scientific studies on the biological activity of S. involucrata are equally numerous. The herb has been shown to have anti-neoplastic, anti-inflammatory, analgesic, anti-oxidative, anti-fatigue, anti-aging, anti-hypoxic, neuroprotective and immunomodulating effects. Many have shown correlations to the traditional clinical applications in Traditional Chinese Medicine and medicines. The possible mechanisms of S. involucrata in treating various cancers are revealed in the article, these include inhibition of cancer cells by affecting their growth, adhesion, migration, aggregation and invasion, inhibition of epidermal growth factor receptor signaling in cancer cells, hindrance of cancer cell proliferation, causing cytotoxicity to cancer cells and promoting expression of tumor suppressor genes. Dosage efficacy is found to be generally concentration- and time-dependent. However, studies on the correlation between particular chemical constituents and specific bioactivities are limited. CONCLUSION: In this review, we have documented the existing traditional uses of S. involucrata and summarized recent research into the phytochemistry and pharmacology of S. involucrata. Many of the traditional uses have been validated by phytochemical and modern pharmacological studies but there are still some areas where the current knowledge could be improved. Although studies have confirmed that S. involucrata has a broad range of bioactivities, further in-depth studies on the exact bioactive molecules and the mechanism of action are expected. Whether we should use this herb independently or in combination deserves to be clarified. The exact quality control as well as the toxicology studies is necessary to guarantee the stability and safety of the clinic use. The sustainable use of this endangered resource was also addressed. In conclusion, this review was anticipated to highlight the importance of S. involucrata and provides some directions for the future development of this plant.
27613811 Distraction First Metatarsophalangeal Arthrodesis With Tricortical Calcaneus Autograft: Te 2016 Dec First metatarsophalangeal joint arthritis can stem from a biomechanical imbalance as in hallux abducto valgus, metabolic arthritidies such as rheumatoid or gout, and even in posttraumatic cases. Advanced arthritis in the foot and ankle can often become debilitating. Surgical intervention is often necessary. Revision of failed first metatarsophalangeal joint arthroplasty is often in the setting of bony erosion and lysis, cystic changes, and loss of bone stock. In this article, we describe first metatarsophalangeal distraction arthrodesis technique using tricortical calcaneus autograft with the aim of simplifying donor site graft harvesting and decreasing donor site morbidity while attaining successful osseous union. LEVELS OF EVIDENCE: Level V.
23962458 Prevalence and incidence rates of psoriatic arthritis in central Norway: data from the Nor 2015 Jan BACKGROUND: A wide range in the prevalence (<0.01-0.25%) and incidence (0.5-23.1/100 000) of psoriatic arthritis (PsA) is reported. The main objective of this study was to examine the prevalence and incidence of PsA in central Norway. METHOD: The patients were recruited from the Nord-Trøndelag Health Study 3, a population study carried out in 2006-2008. All 94 194 inhabitants aged >20 years were invited and 50 806 (54%) responded. The study consisted of a questionnaire (Q1) and a brief medical examination. Q1 included questions if the persons suffered from psoriasis, rheumatoid arthritis (RA) or ankylosing spondylitis (AS). Patients with self-reported psoriasis further answered a specific questionnaire on psoriasis including a questionnaire concerning PsA. In order to identify patients with PsA we used the following criteria: Persons reporting they had or may have PsA; persons answering that they had psoriasis and RA; and persons answering that they had psoriasis and AS. Using this approach, 1278 patients were identified. Hospital files were evaluated by a rheumatologist according to a predefined protocol to verify the diagnosis of PsA. RESULTS: 338 patients, 144 men and 194 women, were verified to have PsA. The prevalence of PsA was 6.7 (95% CI 5.9 to 7.4) per 1000 inhabitants >20 years with no significant difference between men and women. In the 9-year period of 2000-2008, a total of 188 patients were diagnosed with PsA, which give an incidence rate of 41.3/100 000 (35.8-47.6). CONCLUSIONS: The prevalence of PsA in central Norway appears to be higher than previously reported. The reason for this is unknown and may include environmental factors, life style factors and genetic differences.
26950480 Intake of high-fructose corn syrup sweetened soft drinks, fruit drinks and apple juice is 2016 Mar 7 OBJECTIVE: There is a link between joint and gut inflammation of unknown etiology in arthritis. Existing research indicates that regular consumption of high-fructose corn syrup sweetened (HFCS) soft drinks, but not diet soft drinks, may be associated with increased risk of seropositive rheumatoid arthritis (RA) in women, independent of other dietary and lifestyle factors. One unexplored hypothesis for this association is that fructose malabsorption, due to regular consumption of excess free fructose (EFF) and HFCS, contributes to fructose reactivity in the gastrointestinal tract and intestinal in situ formation of enFruAGEs, which once absorbed, travel beyond the intestinal boundaries to other tissues and promote inflammation. In separate studies, the accumulation of advanced glycation end-products has been associated with joint inflammation in RA. Objective of this study was to assess the association between EFF beverages intake and non-age, non-wear and tear-associated arthritis in US young adults. METHODS: In this cross sectional study of 1209 adults aged 20-30y, (Nutrition and Health Examination Surveys 2003-2006) exposure variables were high EFF beverages, including HFCS sweetened soft drinks, and any combination of HFCS sweetened soft drinks, fruit drinks (FD) and apple juice, referred to as tEFF. Analyses of diet soda and diet FD were included for comparison. The outcome was self-reported arthritis. Rao Scott Ҳ(2) was used for prevalence differences and logistic regression for associations, adjusted for confounders. RESULTS: Young adults consuming any combination of high EFF beverages (tEFF) ⩾5 times/week (but not diet soda) were three times as likely to have arthritis as non/low consumers (odds ratios=3.01; p⩽0.021; 95% confidence intervals=1.20-7.59), independent of all covariates, including physical activity, other dietary factors, blood glucose and smoking. CONCLUSION: EFF beverage intake is significantly associated with arthritis in US adults aged 20-30 years, possibly due to the intestinal in situ formation of enFruAGEs.
25982995 Adenovirus-mediated osteoprotegerin ameliorates cartilage destruction by inhibiting proteo 2015 Oct Our aim is to elucidate the effects of osteoproteogerin (OPG) on cartilage destruction in rats as a model of collagen-induced arthritis (CIA). To establish the CIA model, Sprague Dawley rats were injected with bovine type II collagen solution subcutaneously via the tails. Adenovirus-mediated OPG (Ad-OPG) was then injected intra-articularly either at the beginning of CIA (early OPG treatment) or one week after CIA establishment (late OPG treatment); vehicle or Ad-green fluorescent protein were injected as controls. The rats were killed 4 weeks after treatment. Ankle-joint sections were obtained for histology. Serum samples were collected for enzyme-linked immunosorbent assay. Safranin O staining showed that proteoglycan loss was inhibited in the early and late Ad-OPG groups. Terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining revealed that both early and late Ad-OPG treatments significantly prevented chondrocyte apoptosis in CIA rats. Furthermore, disintegrin and metalloproteinase with thrombospondin motif-5 expression decreased remarkably in the early and late OPG treatment groups. However, the cartilage destruction score, cartilage oligomeric matrix protein level and caspase-3 expression were only decreased in the early Ad-OPG treatment group. Additionally, ankle-joint swelling and the interleukin-1β expression level in CIA rats were not notably altered by Ad-OPG treatment. Taken together, our results suggest that early Ad-OPG treatment has potent protective effects against cartilage destruction during rheumatoid arthritis progression, mainly by reducing proteoglycan loss and chondrocyte apoptosis.
27119518 Minimal physiologically-based pharmacokinetic (mPBPK) model for a monoclonal antibody agai 2016 Jun Therapeutic monoclonal antibodies (mAb) targeting soluble inflammatory cytokines exert their pharmacological effects in rheumatoid arthritis through binding and neutralizing free cytokines in target tissue sites. Therefore suppression of free cytokines in such sites directly relates to the magnitude of therapeutic response. Although the interrelationships between mAb and cytokines have been examined in the systemic circulation, less is known about the interaction of mAb and cytokines in inflamed joints. In the present study, the interplay between the mAb, CNTO 345, and its target IL-6 in serum as well as ankle joint synovial fluid were characterized in collagen-induced arthritic mice. A minimal physiologically-based pharmacokinetic model with target-mediated drug disposition (TMDD) features in serum and ankle joint synovial fluid was developed for the assessment of the TMDD dynamics of CNTO 345 and IL-6. Our model indicates that TMDD kinetics in ankle joints differ greatly from that in serum. The differences can be attributed to the limited tissue distribution of CNTO 345 in ankle joint synovial fluid, the significant rise of the IL-6 baseline in ankle joint synovial fluid in comparison with serum, and the relative time-scales of elimination rates between CNTO 345, free IL-6 and CNTO 345-IL-6 complex in serum and ankle joint synovial fluid.
26431776 Activation of LXR attenuates collagen-induced arthritis via suppressing BLyS production. 2015 Dec B-lymphocyte stimulator (BLyS) plays a critical role in the pathogenesis and progression of rheumatoid arthritis (RA). Liver X receptor (LXR), a nuclear receptor, has an important anti-inflammatory effect. However, it is unclear whether the BLyS expression is regulated by LXR. In this study, we found that treatment with LXR agonist in collagen-induced arthritis (CIA) mice significantly attenuated arthritis progression, and markedly decreased BLyS production in serum and splenocytes as well as the production of serum IFNγ and TGFβ. Activation of LXR in B lymphocytes dramatically suppressed the basal and IFNγ/TGFβ-induced BLyS expression. Moreover, LXR agonist prominently suppressed the binding of NF-κB to BLyS promoter region, and decreased the promoter's transcriptional activity. Additionally, activation of LXR obviously repressed IFNγ-induced STAT1 activation and TGFβ-induced SMAD3 activation. These results indicated that downregulation of BLyS may be a novel mechanism by which LXR ameliorates RA, and LXR/BLyS pathway may serve as a novel target for the treatment of RA.
28003810 Succinate/NLRP3 Inflammasome Induces Synovial Fibroblast Activation: Therapeutical Effects 2016 Clematichinenoside AR (C-AR) is a triterpene saponin isolated from the root of Clematis manshurica Rupr., which is a herbal medicine used in traditional Chinese medicine for the treatment of arthritis. C-AR exerts anti-inflammatory and immunosuppressive properties, but little is known about its action in the suppression of fibroblast activation. Low oxygen tension and transforming growth factor-β (TGF-β1) induction in the synovium contribute to fibrosis in arthritis. This study was designed to investigate the effect of C-AR on synovial fibrosis from the aspects of hypoxic TGF-β1 and hypoxia-inducible transcription factor-1α (HIF-1α) induction. In the synovium of rheumatoid arthritis (RA) rats, hypoxic TGF-β1 induction increased succinate accumulation due to the reversal of succinate dehydrogenase (SDH) activation and induced NLRP3 inflammasome activation in a manner dependent on HIF-1α induction. In response to NLRP3 inflammasome activation, the released IL-1β further increased TGF-β1 induction, suggesting the forward cycle between inflammation and fibrosis in myofibroblast activation. In the synovium of RA rats, C-AR inhibited hypoxic TGF-β1 induction and suppressed succinate-associated NLRP3 inflammasome activation by inhibiting SDH activity, and thereby prevented myofibroblast activation by blocking the cross-talk between inflammation and fibrosis. Taken together, these results showed that succinate worked as a metabolic signaling, linking inflammation with fibrosis through NLRP3 inflammasome activation. These findings suggested that synovial succinate accumulation and HIF-1α induction might be therapeutical targets for the prevention of fibrosis in arthritis.
26295143 Folate Receptor-Targeted Dendrimer-Methotrexate Conjugate for Inflammatory Arthritis. 2015 Aug Generation 5 (G5) poly(amidoamide) (PAMAM) dendrimers are synthetic polymers that have been broadly applied as drug delivery carriers. Methotrexate (MTX), an anti-folate metabolite, has been successfully used as an anti-inflammatory drug to treat rheumatoid arthritis (RA) in the clinic. In this study, we examine the therapeutic efficacy of G5 PAMAM dendrimer methotrexate conjugates (G5-MTX) that also have folic acid (FA) conjugated to the G5-MTX (G5-FA-MTX) to target inflammation-activated folate receptors overexpressing macrophages. These cells are thought to play an important role in the development of RA. With G5 serving as a control, the in vitro binding affinities of G5-FA-MTX and G5-MTX to activated macrophages were assessed in RAW264.7, NR8383 and primary rat peritoneal macrophages. The results indicated that the binding of either conjugate to macrophages was concentration- and temperature-dependent and could be blocked by the presence of 6.25 mM free FA (p < 0.005). The preventive effects of G5-MTX and G5-FA-MTX conjugates on the development of arthritis were explored on an adjuvant-induced inflammatory arthritis model and had similar preventive effects in inflammatory arthritis at a MTX equivalent dose of 4.95 μmol/kg. These studies indicated that when multiples of MTX are conjugated on dendritic polymers, they specifically bind to folate receptor overexpressing macrophages and have comparable anti-inflammatory effects to folate targeted MTX conjugated polymers.
27460490 Inhibitory effect of the extract of Phellodendron amurense ruprecht root on collagen-induc 2017 Oct OBJECTIVE: To investigate whether the dried root of Phellodendron amurense Ruprecht (Phellodendri cortex; PC) extract improves arthritic symptoms through anti-inflammatory and immune-modulatory effects in collagen-induced arthritis in mice. METHODS: Rheumatoid arthritis (RA) was induced in male DBA/1 mice by immunization with type II collagen (ColII). CIA mice were divided into 5 groups (n=10 per a group) with normal, CIA control, PC extract (50 mg/kg and 100 mg/kg)-treated, and meloxicam (50 mg/kg)-treated as the reference drug. The PC extract or meloxicam were administered orally in CIA mice once a day for 14 days after arthritis induction. Arthritic score, levels of anti-ColII IgG(2a) antibody, prostaglandin E(2) (PGE(2)), tumor necrosis factor (TNF)-α, and interleukin (IL)-17 in the sera of CIA mice were measured. Histopathological changes in the ankle joints of CIA mice were also analyzed by staining with hematoxylin and eosin (H and E), safranin-O and immunohistochemistry using anti-TNF-α and anti-IL-17 antibodies. RESULTS: The arthritic score was increased in CIA mice in a time-dependent manner, as were the serum levels of anti-ColII IgG(2a) antibody, PGE(2), TNF-α, and IL-17. However, the oral administration of PC extract at 50 and 100 mg/kg in CIA mice significantly decreased the arthritic scores, and the serum levels of anti-ColII IgG(2a), PGE(2), TNF-α, and IL-17 compared with those in the CIA group (P<0.05 or P<0.01). Furthermore, histopathological improvement of the joint architecture in CIA mice was observed after administration of PC extract. PC extract also significantly inhibited the expression of TNF-α and IL-17 in the joints of CIA mice by suppressing the expression of their mRNA and proteins. CONCLUSION: PC extract may improve the pathological progression of RA through the inhibition of joint destruction by synovial inflammation and immune-stimulation, therefore, it would be a potential anti-arthritic agent in RA.
26895629 Prevalence of musculoskeletal disorders and rheumatic disease in the Warao, Kari'ña, and 2016 Jul This study aimed to estimate the prevalence of musculoskeletal disorders and rheumatic diseases in the Warao, Kari'ña, and Chaima indigenous populations of Monagas State, Venezuela. A cross-sectional, analytical, community-based study was conducted in 1537 indigenous subjects ≥18 years old (38.6 % male, mean age 41.4 ± 17.5 years). The cross-culturally validated Community Oriented Program for the Control of Rheumatic Diseases (COPCORD) diagnostic questionnaire was applied. Subjects with a positive COPCORD diagnosis (either historic or current pain) were evaluated by primary care physicians and rheumatologists. A descriptive analysis was performed and comparisons made using analysis of variance and the chi-square test. Pain in the last 7 days was reported by 32.9 %, with pain intensity, according to a Likert-type scale [no pain, 195 (38.5 %); minimal pain, 231 (45.6 %); strong pain, 68 (13.4 %); intense pain, 5 (0.9 %)], 38.0 % reported historical pain, and 641 (41.7 %) had either historic or current pain. Of the COPCORD-positive subjects, pain most frequently occurred in the knee, back, and hands. Musculoskeletal and rheumatic diseases included osteoarthritis (14.1 %), back pain (12.4 %), rheumatic regional pain syndromes (RRPS) (9.7 %), undifferentiated arthritis (1.5 %), rheumatoid arthritis (1.1 %), and fibromyalgia (0.5 %). Chaima (18.3 %) and Kari'ña (15.6 %) subjects had a high prevalence of osteoarthritis, and Warao subjects had a high prevalence of low back pain (13.8 %). The prevalence of RRPS was high in all three ethnic groups. The Chaima group had the highest prevalence of rheumatic diseases, with 2.0 % having rheumatoid arthritis. This study provides useful information for health care policy-making in indigenous communities.
29624303 [JUVENILE SPONDYLOARTHRITIS]. 2016 Juvenile spondyloartrhritis is a group of multifactorial diseases in which a disturbed interplay occurs between the immune system and environmental factors on a predisposing genetic background, which leads to inflammation and structural damage of the target tissue. First symptoms of jSpA rarely involve the spine, while asymmetrical oligoarthritis of lower extremities, dactylitis, and peripheral enthesitis are much more common. There are many classification criteria for jSpA, but the majority of pediatric rheumatologists currently use the International League Against Rheumatism (ILAR) criteria according to which most patients with jSpA are classified into the enthesitis-related arthritis group of juvenile idiopathic arthritis. To meet these criteria, a patient should have arthritis and/or enthesitis, with two or more symptoms such as sacroiliac joint tenderness and/or inflammatory back pain, HLAB27 genotype, HLA B27 genotype-associated disease in a first- or second-degree relative, uveitis, and male sex with eight or more years of age. Therefore, diagnosis is most oft en made only based on clinical examination and medical history. Anti- nuclear antibodies (ANA), rheumatoid factor (RF), and HLA testing with B27, B7, and DR4 alleles are preferred. Since subclinical gut inflammation is present in many patients, it is recommended to check fecal calprotectin levels. In patients with signs of peripheral enthesitis it is warranted to perform power Doppler musculoskeletal ultrasound (PDUS), and in patients with signs of axial involvement radiographic and contrast-enhanced magnetic resonance imaging. Most patients are treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy, while in refractory cases with peripheral disease synthetic disease- modifying antirheumatic drugs (DMARDs), such as sulfasalazine, are used. In patients with axial involvement, biological DMARDs such as adalimumab, infliximab, and etanercept are obligatory. Although a number of studies gave us a good insight into the disease pathogenesis, the response to treatment and prognosis are still difficult to predict.
27824550 Chikungunya Virus Infection: An Update on Joint Manifestations and Management. 2016 Oct 31 The advent of sophisticated diagnostics has enabled the discovery of previously unknown arthropod-borne viruses like Chikungunya. This infection has become increasingly prevalent in the last 10 years across the Indian Ocean and has been brought to media attention by a recent outbreak in the Caribbean. The outbreak has been aided by a drastic rise in air travel, allowing infected individuals to transport the virus to previously unaffected regions. In addition, a recently documented viral mutation has allowed its transmission by the Aedes albopictus mosquito, therefore facilitating outbreaks in Southern Europe and the USA. The duration and extent of the arthritis seen peri- and post infection has become a topic of academic interest. Although published data are largely observational, there has been a definite increase in original research focusing on this. Symptoms can persist for years, particularly in older patients with pre-existing medical conditions. The etiology is still not fully understood, but viral persistence and immune activation within synovial fluid have been shown in mouse models. There have been no prospective clinical trials of treatment in humans; however, animal trials are in process. The mainstay of treatment remains anti-inflammatories and steroids where necessary. The clinical presentation seems to mimic common rheumatological conditions like rheumatoid arthritis; therefore recent recommendations suggest the use disease-modifying agents as a common practice for the specific syndrome. This review uses recent published data and draws on our own clinical experience to provide an overview of joint complications of Chikungunya infection.
27401665 Three Cases of Spondyloepiphyseal Dysplasia Tarda in One Korean Family. 2016 Sep Spondyloepiphyseal dysplasia (SED) tarda is an inherited skeletal arthropathy. Because SED tarda involves the joints and resemble the clinical findings of chronic arthropathies, this disease is frequently misdiagnosed as juvenile idiopathic arthritis (JIA). We report here on three patients (father and his two daughters) in one family with SED tarda. All patients had back pain and polyarthralgia. Their radiographs revealed typical changes for SED tarda including platyspondyly and dysplastic bone changes. This rare disease has major clinical importance in that it is similar with JIA or rheumatoid arthritis.
32263177 Activated macrophage-targeted dextran-methotrexate/folate conjugate prevents deterioration 2016 Mar 28 Rheumatoid arthritis (RA) is an autoimmune inflammatory disease, leading to articular synovial hyperplasia, cartilage destruction, and bone erosion. In RA pathophysiology, the activated macrophages contribute to the initiation and maintenance of the disease. Folate receptor, an overexpressed receptor on the activated macrophages, becomes a promising target site for RA treatment. In this work, the folate-modified dextran-methotrexate conjugate (noted as Dex-g-MTX/FA) was synthesized with an untargeted dextran-methotrexate prodrug (referred as Dex-g-MTX) as the control. The two prodrugs self-assembled into spherical micelles with both scales of about 90 nm and exhibited sustained MTX release. Dex-g-MTX/FA exhibited more superior cellular uptake mediated by the folate receptor and higher cytotoxicity toward macrophages activated by lipopolysaccharide (LPS) compared with Dex-g-MTX. Moreover, Dex-g-MTX/FA possessed improved biodistribution at the lesion site and stronger remission of RA through the inhibition of proinflammatory cytokines in comparison with both Dex-g-MTX and free MTX. These results demonstrated that the folate-targeted prodrug, i.e., Dex-g-MTX/FA, is a potential strategy for activated macrophage-targeted therapy of RA.
26969825 Pemphigus vulgaris-associated interstitial lung disease. 2016 Jul Autoimmune bullous diseases (AIBDs)-associated interstitial lung disease (ILD) is extremely rare. Pemphigus vulgaris (PV) is an intraepidermal autoimmune blistering disease caused by circulating autoantibodies against desmoglein. To date, PV-associated ILD has rarely been reported in English literature. We report a rare association of PV and ILD. A 53-year-old Chinese female with PV for 8 months developed ILD after a relapse of PV for 2 months due to discontinuation of oral prednisone by herself. She was successfully treated by systemic methylprednisolone. Taken previously reported bullous pemphigoid-associated ILD and linear IgA/IgG bullous dermatosis-associated ILD together, in general, AIBDs-associated ILD occurs when AIBDs relapse or are not controlled, responds well to systemic corticosteroids, and has a relatively better prognosis when compared with rheumatoid arthritis- or dermatomyositis-associated ILD.
26682981 Th17 Cell Pathway in Human Immunity: Lessons from Genetics and Therapeutic Interventions. 2015 Dec 15 The T helper 17 (Th17) cell pathway has been linked by genome-wide association studies to multiple autoimmune diseases. Identification of the genetic causes of primary immunodeficiency diseases revealed that Th17 cells are also critical in host immunity to mucocutaneous candida infections and Staphylococcus aureus. Therapeutic interventions with inhibitors of the different components of the pathway such as interleukin-12 (IL-12), IL-23, IL-17A, and IL-17RA have variably beneficial effects in psoriasis, Crohn's disease, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, non-infectious uveitis, and multiple sclerosis. Thus, whereas Th17 cells are protective against Candida albicans and to a lesser degree Staphylococcus aureus, they are pathogenic in many autoimmune diseases. Here, we compare and contrast the effects of human genetic mutations of and therapeutic interventions targeted at Th17 cell molecules. We discuss that although there are similarities when Th17 cell pathway molecules are modulated, each molecule has unique non-Th17 cell features that lead to different functional outcomes.
26170060 Suppression of RANKL-induced osteoclast differentiation by cilostazol via SIRT1-induced RA 2015 Oct Osteoclasts are bone-specific multinucleated cells generated by differentiation of monocyte/macrophage hematopoietic lineages and degrade bone matrix by secretion of lytic enzymes. The regulation of osteoclast differentiation provides a potential strategy for treatment of bone-lytic damage. In this study, cilostazol, an inhibitor of type III phosphodiesterase, inhibited RANKL [receptor activator of nuclear factor kappa B (RANK) ligand]-induced RANK expression in bone marrow-derived monocyte/macrophage precursors (BMMs) and Raw 264.7 cells by inhibiting PU.1 via SIRT1 activation. RANKL-induced RANK expression was attenuated by cilostazol and rSIRT1 in Raw 264.7 cells, and these were blocked by sirtinol. In line with these, cilostazol elevated SIRT1 mRNA and protein levels in 12-24h and increased SIRT1 activity, and these effects were inhibited by sirtinol. Furthermore, the RANKL-induced nuclear expression of PU.1, a transcription factor required for macrophage differentiation, was suppressed by cilostazol. Additionally, marked RANKL-induced RANK immunofluorescence staining in Raw 264.7 cells was attenuated by cilostazol and rSIRT1, and both attenuations were prevented by sirtinol. Extensive RANK staining of knee synovial tissues in a mouse model of collagen-induced arthritis (CIA) was markedly reduced by cilostazol (30mg/kg/day). In line with these results, both RANKL- and M-CSF-induced differentiation of BMMs to multinucleated TRAP(+) giant cells and resorption pit formation were inhibited by cilostazol associated with a decrease in TRAP (a marker enzyme of osteoclasts) activity. In conclusion, cilostazol activates SIRT1, which suppresses the nuclear translocation of PU.1, and thus, inhibits RANKL-stimulated RANK expression and causes anti-osteoclast formation in BMMs in vitro and in their murine model of CIA.