Latest Research Characterising Arthralgia in the Preclinical Phase of Rheumatoid Arthritis Using MRI Van Steenbergen HW, et al. Ann Rheum Dis. 2015;74:1225–1232. In this study, the authors aimed to describe the clinical and MRI characteristics of patients with clinically suspect arthralgia (CSA). They observed that subclinical MRI inflammation was present in 44% of all patients and that 35% of these patients with CSA had already shown progression to clinical arthritis within at least 4 months of follow-up. The symptoms and characteristics that were studied could not clearly differentiate between patients with CSA with and without MRI inflammation… Methotrexate Restores Regulatory T Cell Function Through Demethylation of the FoxP3 Upstream Enhancer in Patients with Rheumatoid Arthritis Cribbs AP, et al. Arthritis Rheumatol. 2015;67(5):1182–1192. The authors of this study have previously shown that in a cohort of patients with untreated rheumatoid arthritis (RA), suppressive function of Treg cells is defective. In this study, they identified a novel mechanism of action of methotrexate (MTX), in which treatment of patients with RA using MTX restores defective Treg cell function through demethylation of the FOXP3 locus, leading to a subsequent increase in FoxP3 and CTLA-4 expression… Newly Identified Antiatherosclerotic Activity of Methotrexate and Adalimumab: Complementary Effects on Lipoprotein Function and Macrophage Cholesterol Metabolism Ronda N, et al. Arthritis Rheumatol. 2015;67(5):1155–1164. Rheumatoid arthritis (RA) is associated with accelerated atherosclerosis. The reduction in cardiovascular risk that is induced by methotrexate (MTX) and anti-tumor necrosis factor-α agents in RA is considered secondary to their anti-inflammatory action, but their effects on serum lipoprotein function and foam cell formation are unknown. The reduced capacity of high-density lipoprotein (HDL) to promote cell cholesterol efflux and the increased serum cell cholesterol-loading capacity (CLC) demonstrated in RA may contribute to foam cell development. The authors of this study investigated the influence of MTX and adalimumab treatment on serum cholesterol efflux capacity (CEC) and CLC in patients with RA and the in vitro effects of the two drugs on macrophage cholesterol handling… Private Rare Deletions in SEC16A and MAMDC4 May Represent Novel Pathogenic Variants in Familial Axial Spondyloarthritis O’Rielly DD, et al. Ann Rheum Dis. 2015. Genome-wide association studies identify common variants associated with complex genetic diseases. However, variants identified by GWAS typically do not fully account for the estimated heritability of the disease, the so-called missing heritability problem. It is believed that rare and private variants may explain part of the missing heritability. This study identified two such variants in a large multigenerational family with axial spondyloarthritis. TNF-α and IL-6 Differentially Regulate Dkk-1 in the Inflamed Arthritic Joint Yeremenko N, et al. Arthritis Rheumatol. 2015. The fundamental difference between inflammation-related bone change in rheumatoid arthritis (RA) and spondyloarthritis (SpA), is that there is inflammation-associated bone loss in RA, whereas there is inflammation-associated new bone formation in SpA. The Wnt pathway is crucial for such bone changes. It has been previously shown that an inhibitor of the Wnt pathway, Dkk-1, is low in SpA, thus promoting new bone formation. Here the authors demonstrate an inverse correlation between IL-6 and Dkk-1 and speculate that the relative balance plays a role in bone remodeling. The study is a step toward understanding the complex bone changes induced by inflammation. Male and Female Patients with Axial Spondyloarthritis Experience Disease Activity, Physical Function and Quality of Life Differently: Results from the Groningen Leeuwarden Axial Spondyloarthritis Cohort Arends S, et al. Rheumatology (Oxford). 2015. This study confirms a previously reported observation that, although structural damage is more frequent in male patients with SpA including PsA, female patients report more disease activity, more impairment of function, and worse quality of life. ERAP2 is Associated with Ankylosing Spondylitis in HLA-B27-Positive and HLA-B27-Negative Patients Robinson PC, et al. Ann Rheum Dis. 2015. This study confirms the association between ERAP2 and both HLA B*27-negative and B*27-positive ankylosing spondylitis (AS). It is well known that ERAP1 is associated with HLA B*27-positive AS and HLA C*06-positive psoriasis. Aminopeptidase inhibitors that can inhibit ERAP are being developed and in future may be useful in the management of AS, psoriasis, and related diseases. CT-Guided Corticosteroid Injection of the Sacroiliac Joints: Quality Assurance and Standardized Prospective Evaluation of Long-Term Effectiveness over Six Months. Althoff CE, et al. Clin Rheumatol. 2015. Although intra-articular steroid injection to the sacroiliac joints has been used and recommended for the treatment of isolated or persistent noninfectious sacroiliitis, very few studies have formally investigated its effectiveness or efficacy. In this study, patients who received intra-articular injections, as opposed to periarticular injection, had significant reduction in symptoms for at least 6 months. Randomized, Double-Blind, Dose-Escalation Trial of Triptorelin for Ovary Protection in Childhood-Onset Systemic Lupus Erythematosus Brunner HI, et al. Arthritis Rheumatol. 2015;67(5):1377–1385. The authors of this study aimed to determine the dose, length of time needed for ovarian suppression, and safety of triptorelin that is sufficient to maintain complete ovarian suppression in female patients with childhood-onset systemic lupus erythematosus (SLE) who require cyclophosphamide therapy. The study results showed that high doses (120 μg/kg) of triptorelin are needed to achieve and maintain complete ovarian suppression, this dose was well tolerated and a lag time of 22 days after initiation of triptorelin treatment is required before cyclophosphamide therapy is started or continued. Development of the Sjögren’s Syndrome Responder Index, a Data-Driven Composite Endpoint for Assessing Treatment Efficacy Cornec D, et al. Rheumatology (Oxford). 2015. Composite indices, for example, DAS 28, are an easier way to gauge disease activity at a particular point of time. This has become important to assess, especially with the advent of biologic therapies that are costly. The ESSPRI and ESSDAI are some of the outcome measures used for Sjögren syndrome (SS). Both gauge different aspects of SS. Hence, a composite index is needed, and in this study, the investigators have, for the first time, devised a new compostite index called SSRI (SS Responder Index)-30 (30% precent improvement). They found rituximab to be better than placebo by using this index but not infliximab. Increasing use of this index will enable us to conduct clinical trials on some newer drugs like belimumab in a more robust manner. Treatment of Sjögren’s Syndrome Dry Eye using 0.03% Tacrolimus Eye Drop: Prospective Double-Blind Randomized Study Moscovici BK, et al. Cont Lens Anterior Eye. 2015. Dry eye is a significant cause of morbidity in patients with Sjögren syndrome. Apart from artificial tears, cyclosporine has been used in patients with severe dry eyes. Through this study, the investigators have proven the role of tacrolimus eye drops for the same indication. The study duration was 3 months, and it was a double-blind randomized study. The study now calls for more comparative data between cyclosporine and tacrolimus for the same indication. Association of BAFF and IL-17A with Subphenotypes of Primary Sjögren’s Syndrome Deng F, et al. Int J Rheum Dis. 2015. Although the role of B cells is clearer in the pathogenesis of Sjögren syndrome, the exact role of T cells, especially Th17 cells, is still to be determined. Rituximab has been found to be effective in SS and so has belimumab in some recent studies. In this study, the investigators tried to correlate some biomarkers with subsets of SS. They found that increased BAFF levels in the serum correlated with anti-Ro antibodies and globulins while low levels of complements and IL-17A correlated with higher focus scores in the salivary glands. The latter could probably have a role in lymphoma development from SS. Prohibitin is Involved in Patients with IgG4 Related Disease Du H, et al. PLoS One. 2015;110(5):e0125331. IgG4-related disease is a very heterogeneous disease that manifests as autoimmune pancreatitis, pseudotumor of the eye, retroperitoneal fibrosis, aortitis, etc. Currently, the only way to diagnose the condition is by immunohistochemical evidence of IgG4 plasma cells and serum IgG4 assay. The latter is fraught with problems like prozone phenomenon. In this study, the investigators have tried to look at reactivity to many different autoantigens and found antibodies to prohibitin in a good proportion of these patients. This should be a good alternative in cases where serum IgG4 levels may not be high. Upregulation of NLRP3 Inflammasome in the Tears and Ocular Surface of Dry Eye Patients Niu L, et al. PLoS One. 2015. After the discovery of the NLRP3 inflammasome pathway, many of the previously described autoimmune diseases are now being increasingly classified as autoinflammatory syndromes. The investigators have looked at the possible role of this pathway in Sjögren syndrome and indeed they found increased levels of IL-1, IL-18, and caspase-1 in Sjögren syndrome dry eye and upregulation of the NLRP3 pathway in these patients compared to dry eye controls and healthy controls. Would anakinra or rilonacept have a role in the treatment of SS dry eye? Does Starting Allopurinol Prolong Acute Treated Gout? A Randomized Clinical Trial Hill EM, et al. J Clin Rheumatol. 2015;21(3):120–125. Traditionally, allopurinol is not initiated during an acute gout attack to avoid prolonging painful arthritis. The 2012 American College of Rheumatology Guidelines for the Management of Gout suggest that urate-lowering therapy can be started during an acute attack, based on “consensus opinion of experts, case studies, or standard of care.” The aim of this study was to determine whether initiating allopurinol will adversely affect the resolution of acute, treated gout. This is a 28-day, placebo-controlled, double-blind study of allopurinol initiation in patients with acute gout. In this study, allopurinol did not prolong the acute, treated attack. Biomarkers of Early Stage Osteoarthritis, Rheumatoid Arthritis and Musculoskeletal Health   Ahmed U, et al. Sci Rep. 2015;5:9259. There is currently no biochemical test for detection of early-stage osteoarthritis (eOA). Tests for early-stage rheumatoid arthritis (eRA) such as rheumatoid factor (RF) and anticyclic citrullinated peptide (CCP) antibodies require refinement to improve clinical utility. The authors developed robust mass spectrometric methods to quantify citrullinated protein (CP) and free hydroxyproline in body fluids. We detected CP in the plasma of healthy subjects and surprisingly found that CP was increased in patients with eOA and those with eRA whereas anti-CCP antibodies were predominantly present in eRA. A 4-class diagnostic algorithm combining plasma/serum CP, anti-CCP antibody, and hydroxyproline applied to a cohort gave specific and sensitive detection and discrimination of eOA, eRA, other non-RA inflammatory joint diseases, and good skeletal health. Gout and the Risk of Alzheimer’s Disease: A Population-Based, BMI-Matched Cohort Study Lu N, et al. Ann Rheum Dis. 2015. In this large general practice cohort representative of the UK population, the authors found a 24% lower risk of Alzheimer disease (AD) among individuals with a history of gout, after adjustment for age, sex, BMI, socioeconomic status, lifestyle factors, prior CV-metabolic conditions, and use of CV drugs. These findings provide the first general population-based evidence that gout is inversely associated with the risk of developing AD, thus supporting the purported potential neuroprotective role of uric acid, probably through its antioxidative properties. Repeated Exposure to High-Frequency Low-Amplitude Vibration Induces Degeneration of Murine Intervertebral Discs and Knee Joints McCann MR, et al. Arthritis Rheumatol. 2015. High-frequency, low-amplitude whole-body vibration (WBV) is being used to treat a range of musculoskeletal disorders; however, there is surprisingly limited knowledge of its effect(s) on joint tissues. An in vivo mouse model was used to study the effects of repeated exposure to WBV on bone and joint tissues. This study reveals significant negative effects of WBV on joint tissues in a mouse model, findings that suggest the need for future studies examining the effects of WBV on joint health in humans. Relationship Between Structural Joint Damage and Urate Deposition in Gout: A Plain Radiography and Dual-Energy CT Study Dalbeth N, et al. Ann Rheum Dis. 2015;74(6):1030–1036. This study has demonstrated that MSU crystals are frequently present in joints affected by structural joint damage in people with gout. The study design attempted to explore the independent relationships between MSU crystal deposition, tophus formation, and structural joint damage. The findings from this imaging study raise the possibility that intensive urate-lowering therapy may have clinical benefits in the prevention or healing of structural joint damage in people with gout. To date, very few studies have addressed this concept. This study provides further rationale for well-controlled clinical trials examining the effects of therapies that reduce the serum urate concentration to subsaturation levels on structural joint damage in people with early and advanced disease. Dual-Energy CT for the Diagnosis of Gout: An Accuracy and Diagnostic Yield Study Bongartz T, et al. Ann Rheum Dis. 2015;74(6):1072–1077. This study confirms the good overall accuracy of dual-energy CT (DECT) in diagnosing patients with gout. Moreover, DECT can provide important diagnostic information when the current routine diagnostic approach has failed to confirm the presence of MSU crystals. Careful patient selection is important before using DECT as a diagnostic modality, as false-positive/false-negative results are seen in two particular clinical scenarios. Firstly, DECT appears to have limited sensitivity in patients with acute gout and no prior episodes of gouty arthritis. Of patients with early disease, 20% did not demonstrate evidence of MSU deposition on DECT images. Secondly, DECT may have limited specificity in knee OA. Based on the results, the authors concluded that, the current application for DECT appears to be the second-line diagnostic evaluation of patients with possible gouty arthritis in whom polarizing microscopy of SF has failed to confirm a diagnosis. Future studies will have to clarify how the use of DECT in this clinical situation compares with the use of musculoskeletal ultrasound, which may offer a very similar test performance at lower costs…..