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ID PMID Title PublicationDate abstract
27663916 Psoriasis Induced by Anti-Tumor Necrosis Factor Alpha Agents: A Comprehensive Review of th 2016 Aug Tumor necrosis factor alpha (TNF-α) inhibitors revolutionized the management of patients affected by autoimmune diseases such as inflammatory bowel diseases, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis. The biologic agents targeted to block TNF-α such as infliximab, adalimumab, certulizumab pegol, etanercept, and golimumab, have a good safety profile; however, with increasing, broader, and prolonged use, patients could be exposed to an increased risk of adverse reactions including a wide spectrum of dermatological conditions of different etiology and morphology. Among these, of particular interest is the development of skin immune-mediated diseases that seem to be the consequence of the paradoxical inflammation induced by anti-TNF-α therapy. The majority of these lesions are identified as psoriasiform with three main morphologies and different frequency: pustular psoriasis, signs of psoriasis, and guttate; although erythrodermic or inverted psoriasis, among others, may be observed with less frequency. The increased incidence of these dermatological immune-mediated lesions highlight the importance of the skin as a main target of the side effect of anti-TNF-α agents, while the immunopathogenetic hypothesis of these paradoxical effects are quite intriguing. The aim of this review is to collect and to analyze existing knowledge to better understand the pathogenetic mechanism of these complications and suggest new fields of investigation, improve therapeutic strategies of autoimmune diseases, and prevent and/or better address such complications.
27405985 A critical view on cardiovascular risk in systemic sclerosis. 2017 Jan Systemic Sclerosis (SSc) is an autoimmune disorder characterized by microvascular injury and diffuse fibrosis of the skin and internal organs. While macrovascular disease and higher risk for cardiovascular events are well documented in other systemic rheumatic diseases such as rheumatoid arthritis and systemic lupus erythematosus, the presence and extent of atherosclerosis among patients with SSc is yet to be established. Primary cardiac involvement, due to impairment of coronary microvascular circulation and myocardial fibrosis, considerably affects prognosis and life expectancy of individuals with SSc, representing one of the leading causes of death in this population. On the other hand the existence and prevalence of atherosclerotic coronary disease remains an issue of debate as studies comparing structural and morphological markers of atherosclerosis and cardiovascular events between SSc patients and the general population have yielded controversial results. The aim of this review is to summarize recent literature about the prevalence of cardiovascular disease in SSc, review the surrogate markers of CVD that have been evaluated and examine whether common pathogenic mechanisms exist between SSc and macrovascular disease.
26101460 Harnessing the Therapeutic Potential of Th17 Cells. 2015 Th17 cells provide protective immunity to infections by fungi and extracellular bacteria as well as cancer but are also involved in chronic inflammation. The cells were first identified by their ability to produce interleukin 17A (IL-17A) and, subsequently, associated with chronic inflammation and autoimmunity. Th17 cells have some gene profile similarity with stem cells and can remain dormant in mucosal tissues for long periods. Indeed, recent studies suggest that functionally distinct subsets of pro- and anti-inflammatory Th17 cells can interchange phenotype and functions. For development, Th17 cells require activation of the transcription factors STAT3 and RORγt while RUNX1, c-Maf, and Aiolos are involved in changes of phenotype/functions. Attempts to harness Th17 cells against pathogens and cancer using vaccination strategies are being explored. The cells gain protective abilities when induced to produce interferon γ (IFNγ). In addition, treatment with antibodies to IL-17 is effective in treating patients with psoriasis, psoriatic arthritis, and refectory rheumatoid arthritis. Moreover, since RORγt is a nuclear receptor, it is likely to be a potential future drug target for modulating Th17 functions. This review explores pathways through which Th17 subsets are induced, the molecular basis of their plasticity, and potential therapeutic strategies for their modulation in diseases.
24760746 Erythrovirus B19 and autoimmune thyroid diseases. Review of the literature and pathophysio 2015 Jan Erythrovirus B19 (EVB19) has been incriminated, over recent years, in the onset and/or pathogenesis of many diseases, especially autoimmune thyroid diseases. This review of the literature (published over the last 40 years using Pubmed and Science Direct search engines) was designed to define the role of EVB19, particularly in autoimmune thyroid diseases.Two cases of subacute thyroiditis, one case of Graves' disease (associated with type 1 diabetes and rheumatoid arthritis), and one case of Hashimoto's thyroiditis following acute EVB19 infection were reported. A retrospective case-control study in a pediatric population demonstrated the role of EVB19 in Hashimoto's thyroiditis. Four retrospective studies of pathology slides (including PCR, immunohistochemistry or in situ hybridization) and a prospective case-control study on pathology slides demonstrated the presence of EVB19 in thyroid tissue of patients with benign multinodular goiter, Graves' disease, autoimmune thyroiditis (including Hashimoto's thyroiditis), and thyroid cancer. EVB19 can be demonstrated in the thyroid gland in a wide range of diseases. Although acute EVB19 infection could theoretically trigger autoimmune thyroid disease, there is currently no evidence that EVB19 plays a specific role in the pathophysiology of autoimmune thyroid diseases.
26435495 Fatigue in chronic inflammation - a link to pain pathways. 2015 Oct 5 Fatigue is a frequent symptom in several inflammatory diseases, particularly in rheumatic diseases. Elements of disease activity and cognitive and behavior aspects have been reported as causes of fatigue in patients with rheumatoid arthritis. Fatigue could be associated with activity of inflammatory rheumatism. Indeed, biologic agents targeting inflammatory cytokines are effective in fatigue. Fatigue is also associated with pain and depressive symptoms. Different pathways could be involved in fatigue and interact: the immune system with increased levels of pro-inflammatory cytokines (interleukin-1 and -6 and tumor necrosis factor alpha), dysregulation of the hypothalamic-pituitary-adrenal axis and neurological phenomena involving the central and autonomic nervous systems. A pro-inflammatory process could be involved in pain and behavioral symptoms. Inflammation could be a common link between fatigue, pain, and depression.
27564646 A Critical Review of Biosimilars in IBD: The Confluence of Biologic Drug Development, Regu 2016 Oct On February 9, 2016, the Food and Drug Administration Arthritis Advisory Committee recommended by a vote of 21 to 3, that the biosimilar to infliximab, CT-P13, be approved for rheumatoid arthritis and ankylosing spondylitis and, by extrapolation, for all the indications for which infliximab is currently approved, including adult and pediatric ulcerative colitis and Crohn's disease. On April 5, 2016, the Food and Drug Administration concurred with this recommendation and approved CT-P13 (Inflectra; Pfizer Inc.) for all diseases for which infliximab had previously been approved, including adult and pediatric moderate to severe ulcerative colitis and pediatric and adult moderate to severe and fistulizing Crohn's disease. This was despite the absence of any randomized controlled trials studying the infliximab biosimilar in any inflammatory bowel disease. This highly controversial approach has been criticized by various rheumatology and gastroenterology professional societies around the world. This review will cover the stepwise approach to biosimilar development, issues of extrapolation and interchangeability, and conclude with a discussion of the regulatory, intellectual property issues, and financial implications, which will all intersect in the decision and ability to prescribe a biosimilar or reference anti-tumor necrosis factor drug.
26258845 Widespread non-additive and interaction effects within HLA loci modulate the risk of autoi 2015 Sep Human leukocyte antigen (HLA) genes confer substantial risk for autoimmune diseases on a log-additive scale. Here we speculated that differences in autoantigen-binding repertoires between a heterozygote's two expressed HLA variants might result in additional non-additive risk effects. We tested the non-additive disease contributions of classical HLA alleles in patients and matched controls for five common autoimmune diseases: rheumatoid arthritis (ncases = 5,337), type 1 diabetes (T1D; ncases = 5,567), psoriasis vulgaris (ncases = 3,089), idiopathic achalasia (ncases = 727) and celiac disease (ncases = 11,115). In four of the five diseases, we observed highly significant, non-additive dominance effects (rheumatoid arthritis, P = 2.5 × 10(-12); T1D, P = 2.4 × 10(-10); psoriasis, P = 5.9 × 10(-6); celiac disease, P = 1.2 × 10(-87)). In three of these diseases, the non-additive dominance effects were explained by interactions between specific classical HLA alleles (rheumatoid arthritis, P = 1.8 × 10(-3); T1D, P = 8.6 × 10(-27); celiac disease, P = 6.0 × 10(-100)). These interactions generally increased disease risk and explained moderate but significant fractions of phenotypic variance (rheumatoid arthritis, 1.4%; T1D, 4.0%; celiac disease, 4.1%) beyond a simple additive model.
25761849 Costs Versus Benefits of Routine Histopathological Examination in Total Ankle Replacement. 2015 Jul BACKGROUND: Routine histopathological examination has previously been scrutinized as a source of extraneous cost in orthopedic foot and ankle care. As an increasingly prevalent joint replacement operation, total ankle replacement poses a notable cost to the health care market in an era of cost containment. The purpose of this study was to compare the costs and benefits of routine histopathological examination of specimens removed during total ankle replacement. We hypothesized that a new diagnosis would rarely be found and such examination would seldom alter patient care. METHODS: A retrospective review was conducted of all total ankle replacement operations between 2006 and July 2014 at the investigators' institution. Medical records for 90 patients, undergoing a total of 95 total ankle replacement operations, were reviewed to determine the clinical and pathological diagnoses for each operation and, subsequently, the rates of discrepancy and discordance. Professional charges were determined using estimated reimbursement rates for the Current Procedural Terminology (CPT) codes billed: 88304 (level III microscopic examination), 88305 (level IV microscopic examination), and 88311 (decalcification). RESULTS: Degenerative joint disease was diagnosed by the pathologist in 93.7% of cases (89/95), pseudogout in 4.2% (4/95), and rheumatoid arthritis in 2.1% (2/95). The 4 diagnoses of pseudogout were the only cases of new diagnoses based on pathological review. A total of $16,536.81 was spent for examination of all specimens, for an estimated $4,134.20 spent per discrepant diagnosis. Patient care was unaffected by pathological examination. CONCLUSION: A new diagnosis was rarely found by histopathological examination, and patient care remained unaltered in all cases. The costs of routine histopathological examination of tissue specimens removed during total ankle replacement, therefore, outweigh clinical benefits, and such examination should be left to the discretion of the operating surgeon. LEVEL OF EVIDENCE: Level IV, retrospective case series.
27863511 Analysis of complement biomarkers in systemic sclerosis indicates a distinct pattern in sc 2016 Nov 18 BACKGROUND: The complement system has been implicated in pathogenesis of systemic sclerosis (SSc). The goal of the present study was to evaluate improved complement biomarkers in SSc. METHODS: The presence of C4d, reflecting activation of the classical/lectin pathways, C3bBbP corresponding to activation of the alternative pathway, and soluble terminal complement complexes (all complement pathways), was measured in plasma samples by enzyme-linked immunosorbent assay and correlated to clinical parameters. The study included 81 patients with limited cutaneous SSc and 41 with diffuse cutaneous SSc, as well as 47 matched healthy controls and 81 patients with rheumatoid arthritis, 22 with psoriatic arthritis and 20 with ankylosing spondylitis. Skin and kidney biopsies of selected patients were stained to detect deposited C3b as a marker of local complement activation. RESULTS: Biomarkers of activation of all complement pathways were increased in SSc compared with healthy controls and were similar to those in other rheumatic diseases. When patients with SSc were divided into subgroups, a distinct pattern of complement markers was observed in individuals with scleroderma renal crisis (SRC). By functional assay, we confirmed a significant decrease in complement haemolytic activity in SRC vs. non-SRC patients, indicating complement consumption. Further, we detected glomerular deposits of C3b in some patients with SRC. CONCLUSIONS: The data indicate that complement activation is an important feature of SRC.
26678067 Associations between neighbourhood characteristics and community mobility in older adults 2016 Aug PURPOSE: To explore associations between perceptions of neighbourhood built and social characteristics and satisfaction with community mobility in older adults with chronic health conditions. METHOD: Two hundred and thirty-seven community-dwelling adults aged 60 years or more with one or more of arthritis (osteoarthritis or rheumatoid arthritis), chronic obstructive pulmonary disease, diabetes or heart disease completed a cross-sectional, mailed survey. The survey addressed community mobility and 11 neighbourhood characteristics: amenities (three types), problems (six), social cohesion and safety. Analysis involved logistic regression modeling for each neighbourhood characteristic. RESULTS: Satisfaction with community mobility was associated with perception of no traffic problems (OR = 3.0, 95% CI = 1.4-6.2, p ≤ 0.05) and neighbourhood safety (OR = 3.4, 95% CI = 1.2-9.8, p ≤ 0.05), adjusted for age, ability to walk several blocks and depressive symptoms. CONCLUSION: Satisfaction with community mobility is associated with neighbourhood safety and no traffic problems among older adults with chronic conditions. While further research is needed to explore these neighbourhood characteristics in more detail and to examine causation, addressing these neighbourhood characteristics in health services or community initiatives may help promote community mobility in this population. Implications for Rehabilitation Community mobility, or the ability to move about one's community, is a key aspect of participation that enables other aspects of community participation. Good community mobility is associated with perception of no traffic problems and neighbourhood safety among older adults. Considering and addressing a broad range of environmental influences has the potential to improve community mobility in older adults, beyond traditional approaches. Health professionals can work with clients to develop strategies to avoid traffic and safety problems and can work with communities to develop safe spaces within neighbourhoods, to improve community mobility in older adults.
26327814 Triterpenoid Saponin W3 from Anemone flaccida Suppresses Osteoclast Differentiation throug 2015 Excessive bone resorption by osteoclasts within inflamed joints is the most specific hallmark of rheumatoid arthritis. A. flaccida has long been used for the treatment of arthritis in folk medicine of China; however, the active ingredients responsible for the anti-arthritis effects of A. flaccida are still elusive. In this study, W3, a saponin isolated from the extract of A. flaccida was identified as the major active ingredient by using an osteoclast formation model induced by receptor activator of nuclear factor kappa-B ligand (RANKL). W3 dose-dependently suppressed the actin ring formation and lacunar resorption. Mechanistic investigation revealed that W3 inhibited the RANKL-induced TRAF6 expression, decreased phosphorylation of mitogen-activated protein kinases (MAPKs) and IκB-α, and suppressed NF-κB p65 DNA binding activity. Furthermore, W3 almost abrogated the expression of c-Fos and nuclear factor of activated T cells (NFATc1). Therefore, our results suggest that W3 is a potential agent for treating lytic bone diseases although further evaluation in vivo and in clinical trials is needed.
26315529 Alternative Methods for Defining Osteoarthritis and the Impact on Estimating Prevalence in 2016 May OBJECTIVE: Provide a contemporary estimate of osteoarthritis (OA) by comparing the accuracy and prevalence of alternative definitions of OA. METHODS: The Medical Expenditure Panel Survey (MEPS) household component (HC) records respondent-reported medical conditions as open-ended responses; professional coders translate these responses into International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for the medical conditions files. Using these codes and other data from the MEPS-HC medical conditions files, we constructed 3 case definitions of OA and assessed them against medical provider diagnoses of ICD-9-CM 715 (osteoarthrosis and allied disorders) in a MEPS subsample. The 3 definitions were 1) strict = ICD-9-CM 715; 2) expanded = ICD-9-CM 715, 716 (other and unspecified arthropathies) OR 719 (other and unspecified disorders of joint); and 3) probable = strict OR expanded + respondent-reported prior diagnosis of OA or other arthritis excluding rheumatoid arthritis. RESULTS: Sensitivity and specificity of the 3 definitions, respectively, were 34.6% and 97.5% for strict, 73.8% and 90.5% for expanded, and 62.9% and 93.5% for probable. CONCLUSION: The strict definition for OA (ICD-9-CM 715) excludes many individuals with OA. The probable definition of OA has the optimal combination of sensitivity and specificity relative to the 2 other MEPS-based definitions and yields a national annual estimate of 30.8 million adults with OA (13.4% of US adult population) for 2008-2011.
25938977 Effect of ebosin on modulating interleukin-1β-induced inflammatory responses in rat fibro 2016 The interleukin-1β-mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways are involved in the pathogenesis of rheumatoid arthritis. Ebosin, a novel exopolysaccharide (EPS), exhibits anti-inflammatory activity in rat collagen-induced arthritis by suppressing the production of tumor necrosis factor-α, interleukin-6 and interleukin-1β. The aim of the present study was to assess the effects of ebosin on NF-κB and MAPK signaling pathways mediated through interleukin-1β in rat fibroblast-like synoviocytes (FLSs). Western blotting showed decreased production of phosphorylated p38, JNK1, JNK2, IKKα, IKKβ and IκB in the cytoplasm and NF-κB in the nucleus upon ebosin treatment. The DNA-binding activity of NF-κB in the cell nucleus was also inhibited by ebosin treatment, as demonstrated using an electrophoresis mobility gel shift assay. Analysis of the results of the immunofluorescence assay also showed a reduced amount of NF-κB in the nucleus of cells affected by ebosin. These results provided evidence for the effects of ebosin on both interleukin-1β-mediated MAPK and NF-κB signaling pathways in rat FLSs. In addition, enzyme-linked immunosorbent assay demonstrated that ebosin reduces the levels of matrix metalloproteinases MMP-1 and MMP-3 and the chemokines, interleukin-8 and RANTES. Thus, the results of the present study provide further evidence for understanding the medicinal activity of ebosin at a molecular level, therefore nominating this EPS as a potential therapeutic candidate for the treatment of rheumatic arthritis.Cellular & Molecular Immunology advance online publication, 4 May 2015; doi:10.1038/cmi.2015.36.
26066294 Rituximab use in young adults diagnosed with juvenile idiopathic arthritis unresponsive to 2015 Nov Juvenile idiopathic arthritis (JIA) is the most common rheumatic disease in childhood. Without an effective therapy, patients may progress quickly to functional disability. Recently, depletion of B cells emerged as a new approach for the treatment of autoimmune diseases, including JIA. We describe six cases of JIA patients followed at a referral center for Rheumatology and Pediatric Rheumatology, submitted to treatment with rituximab (RTX) after refractoriness to three anti-TNF agents. Patients received RTX cycles with two infusions every six months. Response to treatment was assessed by DAS28, HAQ/CHAQ, and an overall assessment by the doctor and the patient. Of our six patients, four were girls (mean age at onset of disease: 6.1 years; mean disease evolution time: 15.1 years; mean age upon receiving RTX: 21.6 years). Four patients belonged to polyarticular subtype (1 rheumatoid factor [RF]-negative, 3 FR-positive), a patient with systemic JIA subtype with a polyarticular course and arthritis related to enthesitis. Of our six patients, five responded to treatment; and during the course of 12 months, the clinical response was maintained, although not sustained. However, discontinuation by infusion reactions caused the withdrawal of RTX in two patients. The use of RTX in JIA is restricted to cases refractory to other biological agents and, even considering that this study was held in a small number of advanced patients, RTX proved to be an effective therapeutic option.
26518873 Regulation of Hyaluronan (HA) Metabolism Mediated by HYBID (Hyaluronan-binding Protein Inv 2015 Dec 25 Regulation of hyaluronan (HA) synthesis and degradation is essential to maintenance of extracellular matrix homeostasis. We recently reported that HYBID (HYaluronan-Binding protein Involved in hyaluronan Depolymerization), also called KIAA1199, plays a key role in HA depolymerization in skin and arthritic synovial fibroblasts. However, regulation of HA metabolism mediated by HYBID and HA synthases (HASs) under stimulation with growth factors remains obscure. Here we report that TGF-β1, basic FGF, EGF, and PDGF-BB commonly enhance total amount of HA in skin fibroblasts through up-regulation of HAS expression, but molecular size of newly produced HA is dependent on HYBID expression levels. Stimulation of HAS1/2 expression and suppression of HYBID expression by TGF-β1 were abrogated by blockade of the MAPK and/or Smad signaling and the PI3K-Akt signaling, respectively. In normal human skin, expression of the TGF-β1 receptors correlated positively with HAS2 expression and inversely with HYBID expression. On the other hand, TGF-β1 up-regulated HAS1/2 expression but exerted only a slight suppressive effect on HYBID expression in synovial fibroblasts from the patients with osteoarthritis or rheumatoid arthritis, resulting in the production of lower molecular weight HA compared with normal skin and synovial fibroblasts. These data demonstrate that although TGF-β1, basic FGF, EGF, and PDGF-BB enhance HA production in skin fibroblasts, TGF-β1 most efficiently contributes to production of high molecular weight HA by HAS up-regulation and HYBID down-regulation and suggests that inefficient down-regulation of HYBID by TGF-β1 in arthritic synovial fibroblasts may be linked to accumulation of depolymerized HA in synovial fluids in arthritis patients.
26077415 Incidence and Management of Infusion Reactions to Infliximab in a Prospective Real-world C 2015 Jul OBJECTIVE: Infliximab (IFX) is a therapeutic monoclonal antibody targeting tumor necrosis factor-α indicated in the treatment of chronic inflammatory diseases. IFX is administered by intravenous infusion and may be associated with different types of infusion reactions. METHODS: RemiTRAC Infusion (NCT00723905) is a Canadian observational registry in which patients receiving IFX are followed prospectively to document premedication use, adverse events, infusion reactions, and the management of infusion reactions. The primary endpoint was to assess factors associated with infusion reactions. RESULTS: There were 1632 patients enrolled and 24,852 infusions recorded. Most patients (63.1%) were treated for rheumatologic conditions such as rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis. Of the 1632 patients, 201 (12.3%) reported at least 1 infusion reaction. Three hundred twenty-two infusions were associated with an infusion reaction (1.3%), and most were mild to moderate in severity (95%). The most common infusion reactions were pruritus (19.9%), flushing (9.9%), or dyspnea (6.2%). Multivariate analysis showed that antihistamines premedication, number of previous infusion reactions, and female sex were significantly associated with an increased incidence of infusion reactions (p < 0.0011). The use of any concomitant immunosuppressant or corticosteroids did not influence the incidence of infusion reactions. Antihistamine premedication was associated with an increased incidence of infusion reactions (OR 1.58, p = 0.0007). CONCLUSION: This registry shows that in community-based infusion clinics, infusion reactions to IFX are uncommon and mild to moderate in nature. Antihistamines, intravenous steroids, and acetaminophen are widely used as preventative premedication, although this study showed an absence of benefit with their use.
25829761 Anti-arthritic activity of Fu-Fang-Lu-Jiao-Shuang on collagen-induced arthritis in Balb/c 2015 Apr BACKGROUND: Rheumatoid arthritis (RA) is a common, autoimmune disorder characterized by progressive multiple joint destruction, deformity, disability and premature death in most patients. Fu-Fang-Lu-Jiao-Shuang (FFLJS) is an effective traditional Chinese medicine, which has long been used clinically to treat RA patients. OBJECTIVE: The objective of this study is aimed to evaluate the anti-rheumatic effects of FFLJS on collagen induced arthritis (CIA) model, as well as the underlying mechanisms, which have not previously been explored. MATERIALS AND METHODS: CIA was induced by immunization with type II collagen (CII) in male Balb/c mice. The mice in the onset of arthritis were treated daily with FFLJS (125 or 500 mg/kg) or 1% carboxymethyl cellulose-Na for 28 days. Paw thickness and arthritic score were evaluated to confirm the anti-arthritic effect of FFLJS on CIA in mice. Levels of anti-CII antibody, proinflammatory cytokines interleukin-1 (IL-1) β, IL-17, and tumor necrosis factor-α (TNF-α) as well as prostaglandin E-2 (PGE-2) in serum and histological changes in the ankle joint were also analyzed. In addition, expressions of matrix metalloproteinases-1 (MMP-1), MMP-3 and tissue inhibitors of matrix metalloproteases-1 (TIMP-1) in synovial tissue were also detected to further study the molecular mechanism of the anti-arthritic effects of FFLJS. RESULTS: During therapeutic treatment, FFLJS significantly reduced paw thickness and arthritic score in CIA mice, decreased the amounts of TNF-α, IL-1 β, IL-17, PGE-2 and anti-CII antibody in serum. In addition, FFLJS treatment could prevent the bone destruction by reducing the expression of MMP-1 and MMP-3, increasing the expression of TIMP-1 in synovial tissue of CIA mice. CONCLUSION: These findings offer the convincing evidence for the first time that the anti-rheumatic effects of FFLJS might be related to down-regulation of TNF-α, IL-1 β, IL-17 and PGE-2 levels for acute arthritis, and regulation of MMP-1, MMP-3 and TIMP-1 protein expression for chronic arthritis.
26147757 Neutrophils in pediatric autoimmune disease. 2015 Sep PURPOSE OF REVIEW: As first immune responders, neutrophils are essential mediators of host defense, and also contribute to chronic pathologic inflammation at the crossroads of innate and adaptive immunity. In this review, we will highlight the current understanding of the role of neutrophils in pediatric rheumatology, with a focus on juvenile idiopathic arthritis (JIA) and lupus. RECENT FINDINGS: In inflamed tissues, neutrophils extrude neutrophil extracellular traps containing autoantigen that potentially drives lupus and rheumatoid factor-positive JIA. However, the contribution of neutrophil extracellular traps to pathogenesis remains an area of intense investigation. In JIA joints, neutrophils are activated to such an extent that associated circulating levels of S100A proteins may serve as biomarkers, correlating with disease activity, predicting response to treatment and heralding flares. Beyond the effects of 'normal' activation, neutrophils in JIA and lupus display dysregulation in gene expression, subset activation, and apoptosis. SUMMARY: The role of neutrophils in pediatric rheumatology is an understudied area, but garnering increasing attention. Although clearly implicated in JIA and lupus, the specific contributions of neutrophils to pathogenesis and the use of neutrophil activity surrogates as biomarkers require further study. Clarification of these outstanding issues will have implications for diagnosis and treatment of pediatric rheumatologic conditions.
27502365 Whipple's arthritis. 2016 Dec Whipple's disease is a chronic systemic infection that is due to the bacterial agent Tropheryma whipplei and can be cured by appropriate antibiotic therapy. The typical patient is a middle-aged man. Rheumatologists are in a prime position to handle Whipple's disease. The classical presentation combines weight loss and diarrhea, preceded in three-quarters of patients by a distinctive pattern of joint manifestations that run an intermittent course, at least initially. The mean time from joint symptom onset to the diagnosis of Whipple's disease is 6 years. Either oligoarthritis or chronic polyarthritis with negative tests for rheumatoid factors (RFs) develops. If the diagnosis is missed, progression to chronic septic destructive polyarthritis may occur. Spondyloarthritis has also been reported, as well as a few cases of diskitis or, even more rarely, of hypertrophic osteoarthropathy. In most patients with the classical form of Whipple's disease, periodic acid-Schiff (PAS) staining of duodenal and jejunal biopsies shows macrophagic inclusions that contain bacteria. However, the involvement of the bowel may be undetectable clinically or, less often, histologically, and even PCR testing of bowel biopsies may be negative. Therefore, when nothing points to bowel disease, rheumatologists should consider T. whipplei infection in middle-aged men with unexplained intermittent oligoarthritis. PCR testing allows the detection of T. whipplei genetic material in joint fluid, saliva, and feces. This test is now a first-line diagnostic investigation, although T. whipplei is a rare cause of unexplained RF-negative oligoarthritis or polyarthritis in males. PCR testing can provide an early diagnosis before the development of severe systemic complications, which are still fatal in some cases.
27273608 Brief Report: Anti-Eukaryotic Initiation Factor 2B Autoantibodies Are Associated With Inte 2016 Nov OBJECTIVE: To investigate novel systemic sclerosis (SSc) autoantibodies in autoantibody-negative patients and establish clinical associations. METHODS: Serum samples and clinical data for 548 patients with SSc were collected. Routine serologic techniques were used to test the serum samples for known SSc autoantibodies, and samples with negative results were further investigated by radiolabeled-protein immunoprecipitation assay. Sera that immunoprecipitated a novel 30-kd band were analyzed by indirect immunofluorescence and immunoprecipitation, using depleted cell extracts to establish a common reactivity. Mass spectrometry was performed to identify the novel autoantigen, and the results were confirmed using commercial antibodies. Sera from 426 patients with other forms of connective tissue disease, 103 with rheumatoid arthritis, 114 with idiopathic interstitial lung disease (ILD), and 150 healthy subjects were serotyped as controls. RESULTS: A novel autoantigen with a molecular weight of ∼30 kd was recognized by 7 sera from patients with SSc, 6 of whom had ILD, and by no controls. Six of the patients had diffuse cutaneous involvement, and 4 had overlap features with other autoimmune diseases. Immunodepletion experiments indicated that all samples targeted the same autoantigen, and mass spectrometry identified the novel autoantigen as eukaryotic initiation factor 2B (eIF2B). CONCLUSION: We report the identification of a novel autoantibody (anti-eIF2B) in a small number of patients with SSc (∼1%); this autoantibody is closely associated with diffuse cutaneous manifestations and the presence of ILD.