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ID PMID Title PublicationDate abstract
27796880 Telocytes in Chronic Inflammatory and Fibrotic Diseases. 2016 Telocytes are a peculiar stromal (interstitial) cell type implicated in tissue homeostasis and development, as well as in the pathophysiology of several disorders. Severe damage and reduction of telocytes have been reported during fibrotic remodeling of multiple organs in various diseases, including scleroderma, Crohn's disease, ulcerative colitis, and liver fibrosis, as well as in chronic inflammatory lesions like those of primary Sjögren's syndrome and psoriasis. Owing to their close relationship with stem cells, telocytes are also supposed to contribute to tissue repair/regeneration. Indeed, telocytes are universally considered as "connecting cells" mostly oriented to intercellular signaling. On the basis of recent promising experimental findings, in the near future, telocyte transplantation might represent a novel therapeutic opportunity to control the evolution of chronic inflammatory and fibrotic diseases. Notably, there is evidence to support that telocytes could help in preventing abnormal activation of immune cells and fibroblasts, as well as in attenuating the altered matrix organization during the fibrotic process. By targeting telocytes alone or in tandem with stem cells, we might be able to promote regeneration and prevent the evolution to irreversible tissue injury. Besides exogenous transplantation, exploring pharmacological or non-pharmacological methods to enhance the growth and/or survival of telocytes could be an additional therapeutic strategy for many disorders.
26876186 Interferon gamma-inducible protein 16 (IFI16) and anti-IFI16 antibodies in primary Sjögre 2015 Dec 30 The interferon (IFN) signature, namely the overexpression of IFN-inducible genes is a crucial aspect in the pathogenesis of primary Sjögren's syndrome (pSS). The IFN-inducible IFI16 protein, normally expressed in cell nuclei, may be overexpressed, mislocalized in the cytoplasm and secreted in the extracellular milieu in several autoimmune disorders including pSS. This leads to tolerance breaking to this self-protein and development of anti-IFI16 antibodies. The aim of this study was to identify pathogenic and clinical significance of IFI16 and anti-IFI16 autoantibodies in pSS. IFI16 and anti-IFI16 were assessed in the serum of 30 pSS patients and one-hundred healthy donors (HD) by ELISA. IFI16 was also evaluated in 5 minor salivary glands (MSGs) of pSS patients and 5 MSGs of non-pSS patients with sicca symptoms by immunohistochemistry. Normal MSGs do not constitutively express IFI16. Conversely, in pSS-MSGs a marked expression and cytoplasmic mislocalization of IFI16 by epithelial cells was observed with infiltrations in lymphocytes and peri/ intra-lesional endothelium. pSS patients display higher serum levels of both IFI16 and anti-IFI16 autoantibodies compared to HD. Our data suggest that IFI16 protein may be involved in the initiation and perpetuation of glandular inflammation occurring in pSS.
27143947 Generation and characterization of ixekizumab, a humanized monoclonal antibody that neutra 2016 Interleukin (IL)-17A exists as a homodimer (A/A) or as a heterodimer (A/F) with IL-17F. IL-17A is expressed by a subset of T-cells, called Th17 cells, at inflammatory sites. Most cell types can respond to the local production of IL-17A because of the near ubiquitous expression of IL-17A receptors, IL-17RA and IL-17RC. IL-17A stimulates the release of cytokines and chemokines designed to recruit and activate both neutrophils and memory T-cells to the site of injury or inflammation and maintain a proinflammatory state. IL-17A-producing pathogenic T-cells contribute to the pathogenesis of autoimmune diseases, including psoriasis, psoriatic arthritis, rheumatoid arthritis, and ankylosing spondylitis. This study describes the generation and characterization of ixekizumab, a humanized IgG4 variant IL-17A-neutralizing antibody. Ixekizumab binds human and cynomolgus monkey IL-17A with high affinity and binds rabbit IL-17A weakly but does not bind to rodent IL-17A or other IL-17 family members. Ixekizumab effectively inhibits the interaction between IL-17A and its receptor in binding assays and potently blocks IL-17A-induced GRO or KC secretion in cell-based assays. In an in vivo mouse pharmcodynamic model, ixekizumab blocks human IL-17A-induced mouse KC secretion. These data provide a comprehensive preclinical characterization of ixekizumab, for which the efficacy and safety have been demonstrated in human clinical trials in psoriasis and psoriatic arthritis.
26440935 The prevalence of monosodium urate and calcium pyrophosphate crystals in synovial fluid fr 2016 Mar The aim of this study was to assess the frequency of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in synovial fluids (SFs) aspirated from wrist and finger joints of patients with previously diagnosed joint diseases. We reviewed the results of SF analysis of 1593 samples and identified 126 patients with effusions in the small joints of the hands and wrists. We reported from patients' medical files data about sex, age, diagnosis, disease duration and the microscopic SF results. The prevalence of CPP crystals in SF was 85.71% in CPP-crystals arthritis (CPP-CA), 19.35% in rheumatoid arthritis (RA), 13.89% in osteoarthritis (OA) and 0% in psoriatic arthritis (PsA), spondyloarthritis (SpA), gout and miscellanea. The prevalence of MSU crystals in SF was 83.3% in gout, 10% in PsA, 2.8% in OA and 0% in RA, SpA, miscellanea and CPP-CA. Consistent with previously reported data concerning the big joints, microcrystals can be frequently found also in the small joints of patients with previous diagnosis. The finding underlines the importance of analyzing SF from the hand and wrist joints in the attempt to identify comorbidities associated with the presence of crystals and to develop targeted treatment strategies.
27384449 Dual anti-neutrophil cytoplasmic antibody-related pauci-immune crescentic glomerulonephrit 2016 Sep Sjögren's syndrome is an autoimmune disease that primarily affects exocrine glands. Renal involvement of Sjögren's syndrome may lead to tubulointerstitial disease, whereas secondary glomerulopathies such as anti-neutrophil cytoplasmic antibody (ANCA)-related pauci-immune crescentic glomerulonephritis are rarely observed. In addition, crescent glomerulonephritis that is simultaneously positive for both myeloperoxidase (MPO)-ANCA and proteinase 3 (PR3)-ANCA has never been reported in Sjögren's syndrome. Here, we report a case of pauci-immune crescentic glomerulonephritis exhibiting positivity for both MPO- and PR3-ANCAs in a patient with primary Sjögren's syndrome. A 71-year-old female was hospitalized for cough, blood-tinged sputum, and dyspnea two weeks after diagnosis with Sjögren's syndrome. On admission, serum anti-nuclear antibody, anti-Ro/SS-A antibody, MPO-ANCA, and PR3-ANCA were all positive, and serum blood urea nitrogen and creatinine (Cr) levels were 42.7 and 2.9 mg/dL, respectively. On the seventh day of hospitalization, the patient's serum Cr level was 5.7 mg/dL, indicating rapidly progressive glomerulonephritis. Renal biopsy resulted in the diagnosis of ANCA-related pauci-immune crescentic glomerulonephritis, for which intravenous methylprednisolone (7 mg/kg/day) was administered for three consecutive days, followed by combination therapy with oral prednisolone (1 mg/kg/day) and intravenous cyclophosphamide (500 mg/m(2)). The patient was positive in the Schirmer's I test, and a salivary gland biopsy showed sialadenitis with lympho-plasmacytic infiltrations. On day 28 of hospitalization, the patient was discharged after amelioration of respiratory symptoms and azotemia. At 6 months after discharge, the patient continued to receive appropriate daily medications and was negative for both MPO- and PR3-ANCAs, with a slight elevation in serum Cr levels.
26857698 Genome-wide DNA methylation analysis in multiple tissues in primary Sjögren's syndrome re 2016 Nov OBJECTIVES: Increasing evidence suggests an epigenetic contribution to the pathogenesis of autoimmune diseases, including primary Sjögren's Syndrome (pSS). The aim of this study was to investigate the role of DNA methylation in pSS by analysing multiple tissues from patients and controls. METHODS: Genome-wide DNA methylation profiles were generated using HumanMethylation450K BeadChips for whole blood, CD19+ B cells and minor salivary gland biopsies. Gene expression was analysed in CD19+ B cells by RNA-sequencing. Analysis of genetic regulatory effects on DNA methylation at known pSS risk loci was performed. RESULTS: We identified prominent hypomethylation of interferon (IFN)-regulated genes in whole blood and CD19+ B cells, including at the genes MX1, IFI44L and PARP9, replicating previous reports in pSS, as well as identifying a large number of novel associations. Enrichment for genomic overlap with histone marks for enhancer and promoter regions was observed. We showed for the first time that hypomethylation of IFN-regulated genes in pSS B cells was associated with their increased expression. In minor salivary gland biopsies we observed hypomethylation of the IFN-induced gene OAS2. Pathway and disease analysis resulted in enrichment of antigen presentation, IFN signalling and lymphoproliferative disorders. Evidence for genetic control of methylation levels at known pSS risk loci was observed. CONCLUSIONS: Our study highlights the role of epigenetic regulation of IFN-induced genes in pSS where replication is needed for novel findings. The association with altered gene expression suggests a functional mechanism for differentially methylated CpG sites in pSS aetiology.
26245278 IL-17 sequestration via salivary gland gene therapy in a mouse model of Sjogren's syndrome 2015 Aug 6 INTRODUCTION: IL-17 has a putative role in the pathophysiology of Sjogren's syndrome (SS) and has been shown to be upregulated in the salivary glands of affected individuals. Sequestration of IL-17 with Adenoviral-mediated gene therapy has previously shown a benefit upon the SS-like phenotype in the Aec1/Aec2 mouse model. We sought to understand the proteomic consequences of IL-17 sequestration in the salivary gland of this mouse model as a means of illuminating the role of IL-17 in SS-like disease. METHODS: Ultrasound-assisted gene transfer (UAGT) was utilized to express a fusion protein composed of the extracellular portion of the IL-17 receptor fused to fragment of crystallization (Fc) in the submandibular glands of Aec1/Aec2 mice at 8 weeks of age. After confirming expression of the fusion protein and local and systemic sequestration of IL-17, proteomic profiling was performed on submandibular glands of a treated cohort of Aec1/Aec2 animals relative to the background strain and sham-treated animals. RESULTS: The most notable proteomic signatures of IL-17 sequestration on SS-like disease-related proteins were Kallikrein-related peptidases, including the putative autoantigen Klk1b22. IL-17 sequestration also notably led to an isoelectric shift, but not a molecular weight shift, of Kallikrein-1, attributed to phosphorylation. CONCLUSION: Non-viral IL-17 sequestration gene therapy in the salivary gland is feasible and downregulates expression of a putative SS autoantigen in the Aec1/Aec2 mouse.
27317930 H-ferritin and CD68(+) /H-ferritin(+) monocytes/macrophages are increased in the skin of a 2016 Oct Adult-onset Still's disease (AOSD) patients may show an evanescent salmon-pink erythema appearing during febrile attacks and reducing without fever. Some patients may experience this eruption for many weeks. During AOSD, exceptionally high serum levels of ferritin may be observed; it is an iron storage protein composed of 24 subunits, heavy (H) subunits and light (L) subunits. The ferritin enriched in L subunits (L-ferritin) and the ferritin enriched in H subunits (H-ferritin) may be observed in different tissues. In this work, we aimed to investigate the skin expression of both H-and L-ferritin and the number of macrophages expressing these molecules from AOSD patients with persistent cutaneous lesions. We observed an increased expression of H-ferritin in the skin, associated with an infiltrate in the biopsies obtained from persistent cutaneous lesions of AOSD patients. Furthermore, a positive correlation between H-ferritin skin levels as well as the number of CD68(+) /H-ferritin(+) cells and the multi-visceral involvement of the disease was observed. Our data showed an increased expression of H-ferritin in the skin of AOSD patients, associated with a strong infiltrate of CD68(+) /H-ferritin(+) cells. Furthermore, a correlation between the levels of H-ferritin as well as of the number of CD68(+) /H-ferritin(+) cells and the multi-visceral involvement of the disease was observed.
26375433 Abnormal distribution of AQP5 in labial salivary glands is associated with poor saliva sec 2016 OBJECTIVE: To investigate whether aquaporins (AQPs) are involved in salivary gland dysfunction in patients with neuromyelitis optica (NMO) complicated with Sjögren's syndrome (SS). METHODS: Eight primary SS (pSS) patients, four NMO spectrum disorder (NMOsd) patients complicated with SS (NMOsd-SS), and three control subjects were enrolled. Immunohistochemistry of labial salivary glands (LSGs) was performed to determine the expressions of AQP4, AQP5, and tumor necrosis factor-alpha (TNF-α). In vitro expression of AQP5 was examined by Western blotting in cultured primary salivary gland epithelial cells (SGECs). RESULTS: No expression of AQP4 was shown in all LSGs. AQP5 was clearly expressed in the all acini, but the predominant localization of AQP5 in the apical side was diminished in the patients with pSS or NMOsd-SS compared with the controls and tended to be even lower in NMOsd-SS than pSS. The abnormal localization of AQP5 was associated with poor saliva secretion. No difference was found in TNF-α expression in the LSGs between patients with pSS and NMOsd-SS. AQP5 expression of SGECs in vitro was not changed by TNF-α or interleukin-10. CONCLUSIONS: Our results suggest that AQP5 but not AQP4 contributes to salivary secretion in patients with SS including those with NMO complicated with SS.
25790192 Expression of Toll-like receptor -7 and -9 in B cell subsets from patients with primary Sj 2015 INTRODUCTION: Sjögren's syndrome (SS) is a rheumatic autoimmune disease characterized by inflammation of exocrine glands. As autoantibodies are present in a majority of patients, B cells have been suggested to play an important role in onset and development of the disease. Toll-like receptors (TLRs) are pattern recognition receptors triggering innate immune responses. Since an increased expression of TLRs has been detected in other rheumatic diseases the purpose of this study was to explore TLRs in B cells of SS patients. METHODS: The expression of TLR-7 and -9 in B cell subsets of 25 patients with primary SS (pSS) and 25 healthy controls was analysed in peripheral blood using flow cytometry and real time quantitative PCR. RESULTS: We detected similar levels of CD19+ B cells in pSS patients and healthy controls. An increased number of naïve B cells, as well as fewer pre-switched memory B cells were found in pSS patients. No significant differences were observed in TLR-7 and -9 expression in B cells between pSS patients and healthy controls. CONCLUSION: This study shows that pSS patients have an alteration in the B cell subpopulation composition compared to controls, with less pre-switched memory B cells and more naïve B cells. We did not detect any significant disparities in TLR-7 and -9 expression between the two groups.
26826598 Early BAFF receptor blockade mitigates murine Sjögren's syndrome: Concomitant targeting o 2016 Mar Sjögren's syndrome (SS) is a debilitating autoimmune disease. Patients with SS may develop xerostomia. This process is progressive, and there are no therapeutics that target disease etiology. We hypothesized BAFF receptor (BAFFR) blockade would mitigate SS disease development, and neutralization of CXCL13 and BAFF signaling would be more efficacious than BAFFR blockade alone. We treated NOD/ShiLtJ SS mice with soluble BAFF receptor (BAFFR-Fc) or anti-CXCL13/BAFFR-Fc in combination, prior to the development of clinical disease. Our results show treatment with BAFFR-Fc reduced peripheral B cell numbers and decreased sialadenitis. In addition, this treatment reduced total serum immunoglobulin as well as IgG and IgM specific anti-nuclear autoantibodies. NOD/ShiLtJ mice treated with BAFFR-Fc and anti-CXCL13 antibody were protected from salivary deficits. Results from this study suggest blockade of CXCL13 and BAFFR together may be an effective therapeutic strategy in preventing salivary hypofunction and reducing autoantibody titers and sialadenitis in patients with SS.
27965258 A new autoinflammatory and autoimmune syndrome associated with NLRP1 mutations: NAIAD (NLR 2017 Jul OBJECTIVES: Inflammasomes are multiprotein complexes that sense pathogens and trigger biological mechanisms to control infection. Nucleotide-binding oligomerisation domain-like receptor (NLR) containing a PYRIN domain 1 (NLRP1), NLRP3 and NLRC4 plays a key role in this innate immune system by directly assembling in inflammasomes and regulating inflammation. Mutations in NLRP3 and NLRC4 are linked to hereditary autoinflammatory diseases, whereas polymorphisms in NLRP1 are associated with autoimmune disorders such as vitiligo and rheumatoid arthritis. Whether human NLRP1 mutation is associated with autoinflammation remains to be determined. METHODS: To search for novel genes involved in systemic juvenile idiopathic arthritis, we performed homozygosity mapping and exome sequencing to identify causative genes. Immunoassays were performed with blood samples from patients. RESULTS: We identified a novel disease in three patients from two unrelated families presenting diffuse skin dyskeratosis, autoinflammation, autoimmunity, arthritis and high transitional B-cell level. Molecular screening revealed a non-synonymous homozygous mutation in NLRP1 (c.2176C>T; p.Arg726Trp) in two cousins born of related parents originating from Algeria and a de novo heterozygous mutation (c.3641C>G, p.Pro1214Arg) in a girl of Dutch origin. The three patients showed elevated systemic levels of caspase-1 and interleukin 18, which suggested involvement of NLRP1 inflammasome. CONCLUSIONS: We demonstrate the responsibility of human NLRP1 in a novel autoinflammatory disorder that we propose to call NAIAD for NLRP1-associated autoinflammation with arthritis and dyskeratosis. This disease could be a novel autoimmuno-inflammatory disease combining autoinflammatory and autoimmune features. Our data, combined with that in the literature, highlight the pleomorphic role of NLRP1 in inflammation and immunity. TRIAL REGISTRATION NUMBER: NCT02067962; Results.
26345159 The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats. 2015 BACKGROUND: Rheumatoid arthritis (RA), induced by the prolonged inappropriate inflammatory responses, is one of the most prevalent of all chronic inflammatory joint diseases. Curcumin (CM), a yellow hydrophobic polyphenol derived from the herb turmeric, has various pharmacological activities against many chronic diseases and acts by inhibiting cell proliferation and metastasis and downregulating various factors, including nuclear factor kappa B, interleukin-1β and TNF-α. Given the pathogenesis of RA, we hypothesized that the drug also has antiarthritic effects. The aims of the present study included the following: 1) examining the therapeutic effect of CM administered via intravenous (iv) injection on RA and 2) formulating the drug into oil-water nanoemulsions (Ns) to overcome the low oral bioavailability of CM and achieve oral delivery of the drug. METHODS: The effect of CM administered through iv injection on adjuvant-induced arthritis in rats was studied in terms of paw swelling, weight indices of the thymus and spleen, and pathological changes in nuclear factor kappa B expression and inflammatory cytokines. Methotrexate was used as a positive control. The CM-Ns were prepared using a high-pressure homogenizing method and characterized with respect to the particle size and morphology. The stability of the CM-Ns in simulated gastrointestinal (GI) fluids and in vitro release were also investigated. A pharmacokinetic study of the CM-Ns and suspensions in which the plasma levels were determined using an high performance liquid chromatography method and the pharmacokinetic parameters were calculated based on a statistical moment theory was also performed in rats. RESULTS: CM administered via iv injection had a therapeutic effect on RA similar to methotrexate. CM-Ns with a diameter of approximately 150 nm were successfully prepared, and the drug was well encapsulated into the Ns without degradation in simulated GI conditions. The area under the curve (AUC) and Cmax for the CM-Ns were more than threefold greater than those for the suspensions; moreover, similar decreases in the levels of TNF-α and interleukin-1β in both synovial fluid and blood serum were obtained from oral administration of CM-Ns and iv injection. CONCLUSION: CM was an effective antiarthritic agent, and the present N formulation appeared to be a promising system that allowed RA therapy with CM to be converted from iv to oral administration.
27491295 Reactive oxygen species in organ-specific autoimmunity. 2016 Dec Reactive oxygen species (ROS) have been extensively studied in the induction of inflammation and tissue damage, especially as it relates to aging. In more recent years, ROS have been implicated in the pathogenesis of autoimmune diseases. Here, ROS accumulation leads to apoptosis and autoantigen structural changes that result in novel specificities. ROS have been implicated not only in the initiation of the autoimmune response but also in its amplification and spreading to novel epitopes, through the unmasking of cryptic determinants. This review will examine the contribution of ROS to the pathogenesis of four organ specific autoimmune diseases (Hashimoto thyroiditis, inflammatory bowel disease, multiple sclerosis, and vitiligo), and compare it to that of a better characterized systemic autoimmune disease (rheumatoid arthritis). It will also discuss tobacco smoking as an environmental factor endowed with both pro-oxidant and anti-oxidant properties, thus capable of differentially modulating the autoimmune response.
27230848 [Molecular and Cellular Pathogenesis of Cherubism]. 2016 Jun Study of rare genetic disorder often provides fundamental insights into the pathology of common diseases. Cherubism is a rare craniofacial disorder in children characterized by the destruction of maxillary and mandibular bones due to expansile fibrous inflammatory lesions. Genetic study of cherubism families discovered that gain-of-function mutations in the signaling adaptor protein SH3BP2 are responsible for cherubism. Analysis of the mouse model revealed that cherubism is an autoinflammatory disorder that is caused by dysregulated signaling pathway mediated by toll-like receptors and spleen tyrosine kinase. Recent study of the SH3BP2-deficient mice showed that SH3BP2 plays important roles in bone resorption in mouse models of inflammatory arthritis. These results establish SH3BP2 as a key player in the osteoimmune system beyond its role in a rare inherited disorder and suggest that the signaling pathway mediated by SH3BP2 is involved in the pathogenesis of common inflammatory bone diseases such as rheumatoid arthritis.
25519036 [Osteosynthesis of talonavicular fusion with a claw plate and compression screw]. 2015 Jun OBJECTIVE: A new method of osteosynthetic stabilization of talonavicular fusion is presented. INDICATIONS: Idiopathic and posttraumatic talonavicular arthritis, talonavicular destruction in rheumatoid arthritis, adult acquired flatfoot deformity, cavovarus deformity, talonavicular degenerative disease in tarsal coalition. CONTRAINDICATION: Major hindfoot deformity or instability, severe osteopenic conditions of tarsal bones. SURGICAL TECHNIQUE: Talonavicular fusion is stabilized with a medioplantar 6.5-mm lag screw in combination with a dorsolateral 3.5-mm claw plate (Charlotte Claw compression plate; Fa. Wright Medical Technology, Memphis, USA) by a dorsal surgical access. POSTOPERATIVE MANAGEMENT: Nonweight-bearing in a cast or walker for 6 weeks; after radiologic control increasing weight-bearing is allowed. RESULTS: The technique was used in 44 patients, among them 31 cases of isolated talonavicular fusion. Complete bony healing was observed in 42 cases after medium follow-up time of 13.3 months. All 19 cases of isolated talonavicular fusion without posterior tibial tendon dysfunction healed uneventfully; two cases of non-union were observed in 12 patients with posterior tibial tendon dysfunction.
24445386 Early-onset sarcoidosis caused by a rare CARD15/NOD2 de novo mutation and responsive to in 2015 Feb Granulomatous autoinflammatory diseases are monogenic syndromes caused by mutations in the region encoding for the nucleotide-binding domain region of the NOD2/CARD15 gene with subsequent dysregulation of the inflammatory response and formation of noncaseous granulomas. They include Blau syndrome (BS) and early-onset sarcoidosis (EOS); both are clinically and genetically indistinguishable between them and they are the familial (autosomal dominantly inherited) and sporadic forms of the same disease, respectively. We describe a case of EOS, misdiagnosed for 30 years such as "juvenile rheumatoid arthritis" before and "classic sarcoidosis" later. In our patient, we found a new de novo mutation (E383G) in NOD2 that has been reported only in a family of Japanese patients with BS. After long-term follow-up (42 months), infliximab maintained good efficacy and safety without any sign of disease relapse and side effects.
26462365 Perna canaliculus (Green-Lipped Mussel): Bioactive Components and Therapeutic Evaluation f 2015 Perna canaliculus (Green-Lippped Mussel) is found only in New Zealand waters and is cultivated and manufactured for both the food and nutraceutical industry world-wide. P. canaliculus has traditionally been used as a therapeutic to treat various arthralgias in both humans and animals; however, clinical research reports provide conflicting results. Numerous in vitro studies have reported anti-inflammatory activity of the mussel under various conditions and also demonstrated a synergistic effect with pharmaceutical medications such as non-steroidal anti-inflammatory drugs (NSAIDs) with P. canaliculus protecting the gastrointestinal mucosal lining against such medications. It is proposed that the anti-inflammatory activity demonstrated by P. canaliculus is predominantly due to the lipid fraction, however, among the major classes of compounds found in mussel meat, proteins and peptides are the largest with isolates demonstrating various anti-microbial, anti-inflammatory, anti-oxidant, bioadhesive and anti-hypertensive activities. A review of the bioactive components, their function and therapeutic application is outlined in this chapter. Furthermore, we hypothesise and provide supportive evidence that the gastrointestinal microbiota play an important role in disease processes such as Rheumatoid arthritis and Osteoarthritis and also in the efficacy of P. canaliculus in chronic inflammatory conditions. The metabolic capacity of intestinal microbiota can modify bioactive food components altering the hosts' exposure to these components, potentially enhancing or diminishing their health effects. Understanding the interaction of the bioactive compounds in P. canaliculus with commensal and pathogenic bacteria may facilitate the development of novel interventions to control intestinal and extraintestinal inflammation.
27986080 Erratum to: Prevalence, sensitivity and specificity of antibodies against carbamylated pro 2016 Dec 16 Anti-CarP antibodies were detected in 117 patients with RA (37.9%), ACPA in 190 patients (61.4%) and RF in 202 patients (65.3%). Two (2.04%) of the NHS were positive for anti-CarP, one NHS (1.02%) was positive for ACPA and three NHS were positive for RF (3.06%). Among disease controls, anti-CarP antibodies were detected in 33 patients (16.5%), ACPA in 29 patients (14.5%) and RF in 64 patients (32%). In particular, 16.8% of patients with systemic lupus erythematosus and 31.1% of patients with Sjögren syndrome were positive for anti-CarP. The sensitivity of anti-CarP, ACPA and RF was 46.8, 61.8 and 64.4%, respectively and specificity was 91.95, 89.93 and 76.51%, respectively.
27890993 Ankylosing spondylitis and risk of venous thromboembolism: A systematic review and meta-an 2016 Nov BACKGROUND: Several immune-mediated inflammatory disorders, such as rheumatoid arthritis, psoriatic arthritis, and systemic lupus erythematosus have been linked to an increased risk of venous thromboembolism (VTE). However, the data on ankylosing spondylitis (AS) are limited. METHODS: We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio comparing the risk of VTE and possible pulmonary embolism (PE) in patients with AS versus non-AS participants. Pooled risk ratio and 95% confidence intervals were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS: Of 423 potentially relevant articles, three studies met our inclusion criteria and thus, were included in the data analysis. The pooled risk ratio of VTE in patients with AS was 1.60 (95% confidence interval: 1.05-2.44). The statistical heterogeneity of this study was high with an I(2) of 93%. CONCLUSION: Our study demonstrated a statistically significant increased VTE risk among patients with AS.