Inflammatory Arthritis Disorders Research Articles

A case report on sero-negative juvenile idiopathic arthritis progressing to polyarthritis

A group of inflammatory arthritic disorders known as juvenile idiopathic arthritis (JIA) are characterized by arthritis of uncertain origin that first manifests in a child under the age of 16. This is the most common chronic rheumatological disease of childhood. The JIA is present in every country and has an incidence of 1 in 100,000. Despite the absence of a documented etiology, there are a number of genetic and environmental risk factors as well as immunologic abnormalities that can be seen and used to infer information about the pathophysiology of the illness. Although there is no cure, modern therapy can frequently reduce the underlying inflammation and enhance function and symptoms. In this case patient showed complete resolution of symptoms with no signs of recurrence. As a result, it helps patient to live a healthy life.

Glycosylation deficiency of lipopolysaccharide-binding protein and corticosteroid-binding globulin associated with activity and response to treatment for rheumatoid arthritis

BackgroundSerum protein glycosylation is an area of investigation in inflammatory arthritic disorders such as rheumatoid arthritis (RA). Indeed, some studies highlighted abnormalities of protein glycosylation in RA. Considering the numerous types of enzymes, monosaccharides and glycosidic linkages, glycosylation is one of the most complex post translational modifications. By this work, we started with a preliminary screening of glycoproteins in serum from RA patients and controls.MethodsIn order to isolate glycoproteins from serum, lectin wheat germ agglutinin was used and quantitative differences between patients and controls were investigated by LC–MS/MS. Consequently, we focused our attention on two glycoproteins found in this explorative phase: corticosteroid-binding globulin (CBG) and lipopolysaccharide-binding protein (LBP). The subsequent validation with immunoassays was widened to a larger number of early RA (ERA) patients (n = 90) and well-matched healthy controls (n = 90).ResultsWe observed a significant reduction of CBG and LBP glycosylation in ERA patients compared with healthy controls. Further, after 12 months of treatment, glycosylated CBG and LBP levels increased both to values comparable to those of controls. In addition, these changes were correlated with clinical parameters.ConclusionsThis study enables to observe that glycosylation changes of CBG and LBP are related to RA disease activity and its response to treatment.

Challenges of diagnosing and managing polymyalgia rheumatica: a multi-methods study in UK general practice.

Polymyalgia rheumatica (PMR) is one of the most common inflammatory arthritic disorders seen in older individuals. Most patients with PMR are diagnosed and managed exclusively in general practice, yet primary care-focused research is lacking. To identify and explore the challenges of diagnosis and management of PMR in general practice. A multi-methods study in UK primary care. The multi-methods study comprised two complementary studies: a national questionnaire survey of 5000 randomly selected GPs from across the UK; and a qualitative semi-structured telephone interview study of UK GPs. Simple descriptive statistics were used to analyse questionnaire data. A thematic approach was used to analyse verbatim transcripts of the GP interviews. In total, 1249 (25%) GPs responded to the questionnaire survey. From this total, 24 GPs were interviewed for the qualitative study. Features used by GPs to identify PMR were largely in line with current guidance. Diagnosis was found to be challenging, with GPs relying heavily on response to treatment with glucocorticoids. Investigations advised by current British PMR guidance to attempt to rule out other causes for symptoms were not routinely requested. Concerns surrounding ongoing treatment with glucocorticoids were widespread in relation to both potential adverse effects and ongoing monitoring. Focused strategies to investigate and therefore exclude non-PMR differential diagnoses are required for patients with new-onset suspected PMR symptoms. Additionally, ongoing active review for alternative causes for symptoms as well as vigilance for treatment complications needs to be implemented.

Curcumin-loaded colloidal carrier system: formulation optimization, mechanistic insight, ex vivo and in vivo evaluation.

The present work investigated the topical delivery potential of nanoemulsion gel loaded with curcumin (CR). CR nanoemulsion (CR-NE) was prepared by spontaneous emulsification method using oil (Labrafac PG/glyceryl triacetate), surfactant:cosurfactant (Smix) (tween 80/polyethylene glycol [PEG] 400) and water. The pseudo-ternary phase diagrams were constructed and thermodynamic stability testing was performed. Droplet size and zeta potential were evaluated using photon correlation spectroscopy and transmission electron spectroscopy. Six formulations selected with an average droplet size ≤70±2.72 nm showed a fourfold increase in skin permeation as compared to crude CR solution in oil. The formulation CR-NE4 having a flux of 117.04±2.32 µg/cm2/h and with maximum retention (42.87%) was selected, characterized (droplet size =41.13±3.34 nm and zeta potential =−33.1±1.45 mV), and incorporated into gel using carbopol-980 (1% w/v). Skin dynamics analyzed by confocal laser scanning microscopy showed maximum deposition of CR up to a depth of 86.98 µm and was in concordance with differential scanning calorimetry and Fourier transform infrared spectroscopy studies that confirmed lipid bilayer disruption, enhancing permeation. A 28-day anti-arthritic evaluation (body weight, paw edema, tibiotarsal joint thickness, TNF-α and IL-1β levels, and histopathology) on Freund’s complete adjuvant induced arthritic rat model after topical application of CR-NE gel in Wistar rats demonstrated substantial reversal of arthritic symptoms. Thus, CR-NE gel possesses potential for therapeutic effects locally in inflammatory arthritic disorders with improved topical bioavailability.

The MHC Class I Heavy Chain Structurally Conserved Cysteines 101 and 164 Participate in HLA-B27 Dimer Formation

The human leukocyte antigen (HLA)-B27 is strongly associated with a group of inflammatory arthritic disorders known as the spondyloarthropathies (SpAs). The unusual biochemistry of HLA-B27 has been proposed to participate in disease development, especially the enhanced ability of HLA-B27 to form several heavy chain-dimer populations. HLA-B27 possesses three unpaired cysteine (C) residues at position 67, 308, and 325, in addition to the four conserved cysteine residues at p101, 164, 203, and 259. C67 was proposed to participate in dimer formation of recombinant HLA-B27 protein and in vivo heavy chain-dimers. However, the structurally conserved C164 was demonstrated to participate in endoplasmic reticulum (ER) resident heavy chain-dimer formation. We therefore wanted to determine whether these aggregates involve cysteines other than C164 and the basis for the difference between the observed heavy chain-dimer species. We determined that C164 and C101 can form distinct dimer structures and that the heterogenous nature of heavy chain-dimer species is due to differences in both redox status and conformation. Different HLA-B27 dimer populations can be found in physiologically relevant cell types derived from HLA-B27-positive patients with inflammatory arthritis. In addition, HLA-B27 dimer formation can be correlated with cellular stress induction. The use of both mutagenesis and manipulating cellular redox environments demonstrates that HLA-B27 dimerization requires both specific cysteine?cysteine interactions and conformations with differing redox states. HLA-B27 heavy chain-dimerization is a complex process and these findings provide an insight into HLA-B27 misfolding and a potential contribution to inflammatory disease development.

The Oxidative Folding and Misfolding of Human Leukocyte Antigen-B27

The major histocompatibility complex class I molecule human leukocyte antigen (HLA)-B27 is strongly associated with a group of inflammatory arthritic disorders known as the spondyloarthropathies. Many autoimmune diseases exhibit associations with major histocompatibility complex molecules encoded within the class II locus with defined immune responses either mediated by T or B-lymphocytes. Despite the association being known for over 30 years, no defined immune response and target autoantigens have been characterized for the spondyloarthropathies. Thus, the mechanism and role of HLA-B27 in disease pathogenesis remains undetermined. One hypothesis that has recently received much attention has focused around the enhanced propensity for HLA-B27 to misfold and the increased tendency of the heavy chain to dimerize. The misfolding of HLA-B27 has been associated with its redox status and this is postulated to be involved in disease development. Here we discuss the impact of the redox status on HLA-B27 biosynthesis and function.

Rapid acidification and alkylation: Redox analysis of the MHC class I pathway

The technique of rapid acidification and alkylation can be used to characterise the redox status of oxidoreductases, and to determine numbers of free cysteine residues within substrate proteins. We have previously used this method to analyse interacting components of the MHC class I pathway, namely ERp57 and tapasin. Here, we have applied rapid acidification/alkylation as a novel approach to analysing the redox status of MHC class I molecules. This analysis of the redox status of the MHC class I molecules HLA-A2 and HLA-B27, which is strongly associated with a group of inflammatory arthritic disorders referred to as Spondyloarthropathies, revealed structural and conformational information. We propose that this assay provides a useful tool in the study of in vivo MHC class I structure.

Management of Spondyloarthropathy in Asian Countries

Spondyloarthropathy (SpA) comprises a family of chronic inflammatory arthritis disorders, and ankylosing spondylitis (AS) is regarded as the most frequent and severe subtype of SpA. The prevalence of SpA in Chinese is about 0.2-0.3%. Information about the management of SpA is limited in Asian countries. Non-steroidal anti-inflammatory drugs (NSAIDs) are still the medication of choice for relieving the spinal pain and morning stiffness of SpA. Traditional NSAIDs are relatively cheap and more readily available than selective COX-2 inhibitors in Asian countries. Diseasemodifying agents widely used in SpA include sulfasalazine (SSZ), thalidomide, methotrexate (MTX) and leflunomide. SSZ and MTX are the most frequently used in patients with SpA, even though there are few clinical trials to verify their efficacy. Thalidomide is potentially useful in treating severe and refractory AS patients. Tumor necrosis factor (TNF) inhibitors have been shown to be effective in the treatment of AS, but more attention needs to be given to potential tuberculosis (TB) infection. Traditional herbal medicine and acupuncture are also used in relieving pain and improving function in SpA patients in some Asian countries. This review will discuss the current therapeutic strategies for SpA. Keywords: Management, spondyloarthropathy, ankylosing spondylitis, Asia

Sigma SR, a new method of measuring erythrocyte sedimentation rate. Its value in studying the action and interactions of non-steroidal anti-inflammatory agents.

Sigma SR is a new method of measuring erythrocyte sedimentation rate (ESR) and is characterized by an unvarying haematocrit, routinely corrected to 35%, and the sum of 4 sedimentation levels at 20, 30, 40, and 50 minutes. Two studies were carried out in patients with inflammatory arthritic disorders; the first in 25 patients treated with 1800 mg ibuprofen daily for 7 days, and the second in 31 patients treated either with indomethacin alone (150 mg/day) or combined with aspirin (1500 mg/day) for 5 days. In addition to the assessment of clinical parameters, the ESR was measured using the classical Westergren and the sigma SR methods. The results showed that there were little or no changes from baseline values in the ESR using the Westergren method. With the sigma SR method, however, statistically significant changes were recorded after treatment and these correlated with the clinical findings which demonstrated the anti-inflammatory action of ibuprofen and the reduction in activity of indomethacin by aspirin.