Browse

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

ID PMID Title PublicationDate abstract
27085137 Interferon-γ-Induced Unfolded Protein Response in Conjunctival Goblet Cells as a Cause of 2016 Jun Goblet cells (GCs) are specialized secretory cells that produce mucins and a variety of other proteins. Significant conjunctival GC loss occurs in both experimental dry eye models and patients with keratoconjunctivitis sicca due to the induction of interferon (IFN)-γ. With the use of a primary murine culture model, we found that GCs are highly sensitive to IFN-γ with significantly reduced proliferation and altered structure with low concentrations. GC cultures treated with IFN-γ have increased gene expression of Muc2 and Muc5AC but do not express these mucin glycoproteins. We hypothesized that IFN-γ induces endoplasmic reticulum stress and the unfolded protein response (UPR) in GCs. Cultures treated with IFN-γ increased expression of UPR-associated genes and proteins. Increased GRP78 and sXBP1 expression was found in experimental dry eye and Sjögren syndrome models and was GC specific. Increased GRP78 was also found in the conjunctiva of patients with Sjögren syndrome at the gene and protein levels. Treatment with dexamethasone inhibited expression of UPR-associated genes and increased mucin production. These results indicate that induction of UPR by IFN-γ is an important cause of GC-associated mucin deficiency observed in aqueous-deficient dry eye. Therapies to block the effects of IFN-γ on the metabolically active endoplasmic reticulum in these cells might enhance synthesis and secretion of the protective GC mucins on the ocular surface.
26769076 Upregulation of Bpifb1 expression in the parotid glands of non-obese diabetic mice. 2016 Jan OBJECTIVE: To define the increased mRNA expression of Bpifb1, a member of the bactericidal/permeability-increasing protein family, in parotid acinar cells from non-obese diabetic (NOD) mice, an animal model for Sjögren's syndrome. MATERIALS AND METHODS: Parotid acinar cells were prepared from female NOD (NOD/ShiJcl) mice with or without diabetes, as well as from control (C57BL/6JJcl) mice. Total RNA and homogenate were prepared from the parotid acinar cells. Embryonic cDNA from a Mouse MTC(™) Panel I kit was used. The expression of Bpifb1 was determined by cDNA microarray analysis, RT-PCR, real-time PCR, northern blotting and in situ hybridization. RESULTS: The expression of Bpifb1 mRNA was high in parotid acinar cells from diabetic and non-diabetic NOD mice at 5-50 weeks of age. Acinar cells in the C57BL/6 mice had a low expression of Bpifb1 mRNA at an age >8 weeks, but had a relatively high expression in the foetus and infantile stages. CONCLUSIONS: Bpifb1 mRNA is upregulated in parotid acinar cells in NOD mice, but its expression is not related to the onset of diabetes. These findings suggest that high expression levels of Bpifb1 might predict disease traits before the onset of autoimmunity.
26298875 Effectiveness of imaging modalities for screening IgG4-related dacryoadenitis and sialaden 2015 Aug 23 INTRODUCTION: The aim of this study was to clarify the effectiveness of various imaging modalities and characteristic imaging features in the screening of IgG4-related dacryoadenitis and sialadenitis (IgG4-DS), and to show the differences in the imaging features between IgG4-DS and Sjögren's syndrome (SS). METHODS: Thirty-nine patients with IgG4-DS, 51 with SS and 36 with normal salivary glands were enrolled. Images of the parotid and submandibular glands obtained using sonography, 2-[(18)F]-fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT), computed tomography (CT) and magnetic resonance imaging (MRI) were retrospectively analyzed. Six oral and maxillofacial radiologists randomly reviewed the arranged image sets under blinded conditions. Each observer scored the confidence rating regarding the presence of the characteristic imaging findings using a 5-grade rating system. After scoring various findings, diagnosis was made as normal, IgG4-DS or SS, considering all findings for each case. RESULTS: On sonography, multiple hypoechoic areas and hyperechoic lines and/or spots in the parotid glands and obscuration of submandibular gland configuration were detected mainly in patients with SS (median scores 4, 4 and 3, respectively). Reticular and nodal patterns were observed primarily in patients with IgG4-DS (median score 5). FDG-PET/CT revealed a tendency for abnormal (18)F-FDG accumulation and swelling of both the parotid and submandibular glands in patients with IgG4-DS, particularly in the submandibular glands. On MRI, SS had a high score regarding the findings of a salt-and-pepper appearance and/or multiple cystic areas in the parotid glands (median score 4.5). Sonography showed the highest values among the four imaging modalities for sensitivity, specificity and accuracy. There were significant differences between sonography and CT (p = 0.0001) and between sonography and FDG-PET/CT (p = 0.0058) concerning accuracy. CONCLUSIONS: Changes in the submandibular glands affected by IgG4-DS could be easily detected using sonography (characteristic bilateral nodal/reticular change) and FDG-PET/CT (abnormal (18)F-FDG accumulation). Even inexperienced observers could detect these findings. In addition, sonography could also differentiate SS. Consequently, we recommend sonography as a modality for the screening of IgG4-DS, because it is easy to use, involves no radiation exposure and is an effective imaging modality.
24573745 Th17 cells play a critical role in the development of experimental Sjögren's syndrome. 2015 Jun OBJECTIVE: Although Th17 cells have been increasingly recognised as an important effector in various autoimmune diseases, their function in the pathogenesis of Sjögren's syndrome (SS) remains largely uncharacterised. This study aims to determine the role of Th17 cells in the development of experimental SS (ESS). METHODS: The ESS was induced in wildtype and IL-17A knockout (IL-17 KO) C57BL/6 mice immunised with salivary glands (SG) proteins. Phenotypic analysis of immune cells in the draining cervical lymph nodes (CLN) and SG was performed by flow cytometry and immunofluorescence microscopy. To determine the role of Th17 cells in ESS, immunised IL-17 KO mice were adoptively transferred with in vitro-generated Th17 cells and monitored for SS development. The salivary flow rate was measured, whereas inflammatory infiltration and tissue destruction in SG were assessed by histopathology. RESULTS: SG protein-immunised mice developed overt SS symptoms with increased Th17 cells detected in CLN and within lymphocytic foci in inflamed SG. Notably, immunised IL-17 KO mice were completely resistant for SS induction, showing no evidence of disease symptoms and histopathological changes in SG. Adoptive transfer of Th17 cells rapidly induced the onset of ESS in immunised IL-17 KO mice with markedly reduced saliva secretion, elevated autoantibody production and pronounced inflammation and tissue damage in SG. CONCLUSIONS: Our findings have defined a critical role of Th17 cells in the pathogenesis of ESS. Further studies may validate Th17 cell as a potential target for treating SS.
27358392 Lesional CD4+ IFN-γ+ cytotoxic T lymphocytes in IgG4-related dacryoadenitis and sialoaden 2017 Feb OBJECTIVES: IgG4-related disease (IgG4-RD) is a chronic, systemic, inflammatory condition of unknown aetiology. We have recently described clonally expanded circulating CD4(+) cytotoxic T lymphocytes (CTLs) in IgG4-RD that infiltrate affected tissues where they secrete interleukin (IL)-1β and transforming growth factor -β1 (TGF-β1). In this study, we sought to examine the role of CD4(+) CTLs in the pathogenesis of IgG4-related dacryoadenitis and sialoadenitis (IgG4-DS) and to determine whether these cells secrete interferon-gamma (IFN-γ) at lesional sites. METHODS: Salivary glands of 25 patients with IgG4-DS, 22 patients with Sjögren's syndrome (SS), 12 patients with chronic sialoadenitis (CS) and 12 healthy controls were analysed in this study. Gene expression analysis was performed on submandibular glands (SMGs) from five patients with IgG4-DS, three with CS and three healthy controls. Infiltrating CD4(+) CTLs were examined by quantitative multicolour imaging in tissue samples from 20 patients with IgG4-DS, 22 patients with SS, 9 patients with CS and 9 healthy controls. RESULTS: In IgG4-DS tissues, nine genes associated with CD4(+) CTLs were overexpressed. The expression of granzyme A (GZMA) mRNA was significantly higher in samples from patients with IgG4-RD compared with corresponding tissues from SS and healthy controls. Quantitative imaging showed that infiltrating CD4(+) GZMA(+) CTLs were more abundant in patients with IgG4-DS than in the other groups. The ratio of CD4(+)GZMA(+) CTLs in SMGs from patients with IgG4-DS correlated with serum IgG4 concentrations and the number of affected organs. A large fraction of CD4(+)GZMA(+) CTLs in SMGs from patients with IgG4-DS secreted IFN-γ. CONCLUSIONS: The pathogenesis of IgG4-DS is associated with tissue infiltration by CD4(+)GZMA(+) CTLs that secrete IFN-γ.
27864697 Characteristics of primary Sjögren's syndrome patients with IgG4 positive plasma cells in 2017 Jan The purpose of this study was to investigate the characteristics of primary Sjögren's syndrome (pSS) patients with IgG4 positive (IgG4(+)) plasma cell infiltration in labial salivary glands (LSGs). Paraffin sections of LSGs from 336 pSS patients were stained with IgG4 and IgG monoclonal antibodies. According to the infiltration of IgG4(+) plasma cells, patients were divided and clinical and serological characteristics were analyzed and compared. Based on the infiltration of IgG4(+) plasma cells in the LSGs, patients were divided into three subgroups, low IgG4, moderate IgG4, and high IgG4 groups. A negative association between the number of infiltrated IgG4(+) plasma cells and the disease characteristics was observed. We found that the higher the IgG4(+) expression in plasma cells, the lower the positive rates of serum anti-SSA antibodies, anti-SSB antibodies, antinuclear antibodies (ANA), and rheumatoid factor (RF). Besides, patients from the high IgG4 group had the highest frequency of interstitial lung disease (ILD, 30.6%) and tubulointerstitial nephritis (TIN, 13.9%), but the lowest frequency of leucopenia (13.9%), thrombocytopenia (11.1%), and abnormal thyroidal function (0%). PSS patients with different IgG4(+) plasma cells infiltration in the LSGs had distinctive clinical and laboratory characteristics. It may help us to further understand the role of IgG4(+) plasma cells in pSS.
26454804 Increase of Intracellular BAFF in B Cells of Sjögren's Patients Is Not Affected by Decrea 2015 The presence of a broad spectrum of autoantibodies in Sjögren's syndrome (SjS) patients is the result of abnormal B-cell regulation that can be at least partially explained by abnormal BAFF/BAFFR regulation. The objective of this study was to determine both membrane and intracellular expression of BAFF/BAFFR in monocytes and B-cells in peripheral blood of 19 primary Sjögren's syndrome patients and 20 healthy controls using flow cytometry. We also measured sBAFF in serum. Compared to healthy controls, both surface and intracellular expression of BAFF was significantly increased in monocytes and B-cells of SjS patients. Also serum sBAFF level was elevated. Expression of BAFFR on B-cells of SjS patients was surprisingly decreased, but there was no clear increase or decrease within monocytes. Our results indicate that activated monocytes communicate with B-cells via BAFF and BAFFR, so that B-cells are stimulated, but BAFF is also produced to stimulate cells in autocrine way. The decrease of BAFFR expression in SjS patients suggests that there is the mechanism that attempts to take over in order to balance the high level of BAFF.
25530280 The diagnostic value of technetium 99m pertechnetate salivary gland scintigraphy in patien 2015 Mar PURPOSE: To evaluate the diagnostic value of technetium 99m pertechnetate salivary gland scintigraphy in patients with certain salivary gland diseases. MATERIALS AND METHODS: We evaluated 47 patients: 25 with chronic obstructive parotitis, 12 with sialolithiasis, and 10 with Sjögren syndrome. All of the patients underwent preoperative (99m)Tc-pertechnetate salivary gland scintigraphy. Patients with chronic obstructive parotitis also underwent ultrasonography, sialography, and sialoendoscopy; patients with sialolithiasis also underwent ultrasonography and computed tomography; and patients with Sjögren syndrome also underwent ultrasonography and sialography. We made comparisons between (99m)Tc-pertechnetate salivary gland scintigraphy and the other aforementioned diagnostic tests to investigate the role of (99m)Tc-pertechnetate salivary gland scintigraphy in diseases of the salivary glands. RESULTS: In patients with chronic obstructive parotitis, (99m)Tc-pertechnetate salivary gland scintigraphy showed reduced excretion by the affected glands, whereas uptake was nearly normal. Among patients with sialolithiasis, (99m)Tc-pertechnetate salivary gland scintigraphy showed reduced excretion by the affected glands and decreased uptake in 5 patients. In patients with Sjögren syndrome, (99m)Tc-pertechnetate salivary gland scintigraphy showed a decrease in both excretion and uptake by the 4 glands. CONCLUSIONS: Technetium 99m pertechnetate salivary gland scintigraphy played a substantial role in the diagnosis and differential diagnosis of salivary gland diseases.
25257764 The prevalence of systemic autoimmune rheumatic diseases in Canadian pediatric populations 2015 Mar To estimate systemic autoimmune rheumatic disease (SARD) prevalence using administrative data for pediatric populations in four Canadian provinces. Physician billing claims and inpatient hospitalizations from Alberta, Manitoba, Quebec, and Saskatchewan were used to define cases aged ≤18 years with a SARD diagnosis code in: one or more hospitalization, two or more physician visits within 2 years and at least 2 months apart, or one or more physician visit to a rheumatologist. Estimates ranged from 15.9/100,000 in Quebec [95% confidence interval (95% CI) 14.1, 18.0] to 23.0/100,000 in Manitoba (95% CI 17.9, 29.2). SARDs were more common in females than in males across all provinces. There was a slightly higher prevalence among those living in urban compared to rural areas of Alberta (rate difference 14.4, 95% CI 8.6, 20.1) and Saskatchewan (rate difference 13.8, 95% CI 1.0, 26.6). Our results provide population-based prevalence estimates of pediatric SARDs in four Canadian provinces.
25186798 An autopsy case of Balamuthia mandrillaris amoebic encephalitis, a rare emerging infectiou 2015 Feb Balamuthia mandrillaris is an amoeba found in fresh water and soil that causes granulomatous amoebic encephalitis. We report herein an autopsy case of B. mandrillaris amoebic encephalitis, which was definitely diagnosed by PCR. An 81-year-old man, who had Sjögren's syndrome, manifested drowsiness 2 months before his death with progressive deterioration. Neuroimaging demonstrated foci of T2- and fluid-attenuated inversion recovery high and T1 low-intensity with irregular post-contrast ring enhancement in the cerebral hemisphere, thalamus and midbrain. Pathologically, multiple hemorrhagic and necrotic lesions were found in the cerebrum, thalamus, midbrain, pons, medulla and cerebellum, which were characterized by liquefactive necrosis, marked edema, hemorrhage and necrotizing vasculitis associated with the perivascular accumulation of amoebic trophozoites, a few cysts, and the infiltration of numerous neutrophils and microglia/macrophages. The trophozoites were ovoid or round, 10-60 μm in diameter, and they showed foamy cytoplasm and a round nucleus with small karyosome in the center. The PCR and immunohistochemistry from paraffin-embedded brain specimens revealed angioinvasive encephalitis due to B. mandrillaris. Human cases of B. mandrillaris brain infection are rare in Japan, with only a few brief reports in the literature.
25500159 Presence of anti-Ro/SSA antibody may be associated with anti-aquaporin-4 antibody positivi 2015 Jan 15 BACKGROUND: Neuromyelitis optica (NMO) is often associated with systemic autoimmune diseases or serological markers of non-organ-specific autoimmunity, and has been most frequently associated with Sjögren's syndrome and anti-Ro/SSA antibody (SSA-Ab) positivity in Asian populations. OBJECTIVE: We evaluated the clinical significance of anti-Ro/SSA antibody positivity in patients with NMO spectrum disorder (NMOSD). METHODS: We retrospectively collected data from 106 consecutive patients with NMOSD and reviewed clinical features and laboratory findings. All patients underwent tests for SSA-Ab and anti-aquaporin-4 antibody (AQP4-Ab) using cell-based indirect immunofluorescence assays. RESULTS: Among 106 patients, 20 (18.9%) were positive for SSA-Ab. Of 48 AQP4-Ab-positive patients, 18 (37.5%) had SSA-Ab. AQP4-Ab seropositivity was 90.0% in patients positive for SSA-Ab, and 32.6% in patients without SSA-Ab (p<0.001). Presence of SSA-Ab was associated with systemic autoimmune diseases, including Sjögren's syndrome (p<0.001) and systemic lupus erythematosus (p=0.003), and with the presence of non-organ-specific autoantibodies such as anti-nuclear antibody and anti-dsDNA antibody in patients with NMOSD, but was not associated with annualized relapse rate or final Expanded Disability Status Scale score independent of AQP4-Ab positivity. CONCLUSION: We found that the presence of SSA-Ab was highly associated with seropositivity for AQP4-Ab in patients with NMOSD.
27252266 Clinical and serological associations of autoantibodies to the Ku70/Ku80 heterodimer deter 2016 Jul BACKGROUND: Autoantibodies targeting Ku, an abundant nuclear protein with DNA helicase activity, have been reported in patients with systemic autoimmune rheumatic diseases. Little is known about the clinical associations of anti-Ku antibodies, especially when novel diagnostic technologies are used. The objective of the present study was to analyse the prevalence of anti-Ku antibodies in different medical conditions using a novel chemiluminescent immunoassay. PATIENTS AND METHODS: Serum samples from adult patients with systemic lupus erythematosus (SLE, n=305), systemic sclerosis (SSc, n=70) and autoimmune myositis patients (AIM, n=109) were the primary focus of the study. Results were compared with disease controls (rheumatoid arthritis, RA, n=30; infectious diseases, n=17) and healthy individuals (n=167). In addition, samples submitted for routine autoantibody testing from patients referred to a rheumatology clinic (n=1078) were studied. All samples were tested for anti-Ku antibodies by QUANTA Flash Ku chemiluminescent immunoassay (research use only, Inova Diagnostics, San Diego, USA) using full length recombinant human Ku. SLE patient samples were also tested for other autoantibodies. Clinical data of anti-Ku antibody positive patients (high titres) were obtained by retrospective chart review. RESULTS AND FINDINGS: In the disease cohorts, 30/305 (9.8%) SLE, 3/70 (4.3%) systemic sclerosis and 4/109 (3.7%) autoimmune myositis (AIM) patients were positive, respectively. The four positive AIM patients had an overlap myositis syndrome that included two patients with SLE. The three systemic sclerosis (SSc) positive samples had diagnoses of SSc/SLE overlap, diffuse cutaneous SSc, and early edematous phase SSc. In the control cohorts, 2/170 (1.2%) healthy individuals (all low titre), 0/30 (0.0%) (RA) and 0/17 (0.0%) infectious disease patients were positive. The area under the curve values were: 0.75 for SLE vs. controls, 0.68 for SSc vs. controls and 0.37 for AIM vs. CONTROLS: In the rheumatology clinic referral cohort, 12/1078 (1.1%) were positive for anti-Ku antibodies, nine showing low and three high titres. The diagnoses of the three high positive anti-Ku positive patients were: probable SLE, mixed connective tissue disease (MCTD) and ANA positive RA. CONCLUSION: Anti-Ku antibodies detected by chemiluminescent immunoassay are most prevalent in SLE. When found in AIM and SSc, they were associated with overlap syndrome and early SSc.
27478939 C13orf31 (FAMIN) is a central regulator of immunometabolic function. 2016 Sep Single-nucleotide variations in C13orf31 (LACC1) that encode p.C284R and p.I254V in a protein of unknown function (called 'FAMIN' here) are associated with increased risk for systemic juvenile idiopathic arthritis, leprosy and Crohn's disease. Here we set out to identify the biological mechanism affected by these coding variations. FAMIN formed a complex with fatty acid synthase (FASN) on peroxisomes and promoted flux through de novo lipogenesis to concomitantly drive high levels of fatty-acid oxidation (FAO) and glycolysis and, consequently, ATP regeneration. FAMIN-dependent FAO controlled inflammasome activation, mitochondrial and NADPH-oxidase-dependent production of reactive oxygen species (ROS), and the bactericidal activity of macrophages. As p.I254V and p.C284R resulted in diminished function and loss of function, respectively, FAMIN determined resilience to endotoxin shock. Thus, we have identified a central regulator of the metabolic function and bioenergetic state of macrophages that is under evolutionary selection and determines the risk of inflammatory and infectious disease.
26696727 Effects of adjustment of transcranial direct current stimulation on motor function of the 2015 Nov [Purpose] The purpose of this study was to examine the effects of transcranial direct current stimulation (tDCS) applied to the cerebral cortex motor area on the upper extremity functions of hemiplegic patients. [Subjects and Methods] Twenty four Patients with hemiplegia resulting from a stroke were divided into two groups: a tDCS group that received tDCS and physical therapy and a control group that received only physical therapy. A functional evaluation of the two groups was performed, and an electrophysiological evaluation was conducted before and after the experiment. Statistical analyses were performed to verify differences before and after the experiment. All statistical significance levels were set at 0.05. [Results] The results showed that functional evaluation scores for the elbow joint and hand increased after the treatment in both the experimental group and the control group, and the increases were statistically significantly different. [Conclusion] tDCS was effective in improving the upper extremity motor function of stroke patients. Additional research is warranted on the usefulness of tDCS in the rehabilitation of stroke patients in the clinical field.
26700782 [An elderly man presenting polyarthritis diagnosed as chronic tophaceous gout]. 2015 An 85-year-old man was admitted to our hospital for swollen and painful bilateral lower legs and a high fever. He was initially diagnosed with acute cellulitis and treated with antibiotics. Several days after the improvement of his swollen legs, he complained of both shoulder and arm pain. The laboratory data at this time were as follow: C-reactive protein 10.7 mg/dL, uric acid 8.7 mg/dL, and creatinine 1.07 mg/dL. Both rheumatoid factor and anti-CCP antibody were negative. Whole-body gallium scintigraphy showed a high pathological accumulation in both the shoulders and left wrist. As polymyalgia rheumatica was suspected, oral prednisolone (PSL) of 10 mg/day was started. The patient's shoulder pain improved and he was discharged. However, he was hospitalized twice in the next month because of left shoulder, left knee, right arm, and right wrist pain. During the third hospitalization, we found a subcutaneous nodule on right toe. Aspiration material from the nodule was a white paste, showing acicular crystals under the microscope. According to these findings, the nodule was diagnosed as a tophaceous nodule, and recurrent episodes of polyarthritis were diagnosed as chronic tophaceous gout. Low-dose PSL was continued and febuxostat was added. This patient had multiple risk factors for chronic tophaceous gout: obesity, a habit of drinking, diabetes mellitus, hyperlipidemia, congestive heart failure, and interruption of allopurinol treatment. We herein discuss the clinical course of the patient, the interruption of allopurinol treatment and polypharmacy in elderly patients.
26660318 Difficulty with daily activities involving the lower extremities in people with systemic s 2016 Feb The purpose of this study was to examine the extent of lower extremity impairments in motion and strength in people with systemic sclerosis and the relationships of the impairments to limitations in activities of daily living primarily involving the lower extremities. Participants were 69 persons with SSc who received evaluations of lower extremity joint motion (Keitel function test), strength (timed-stands test), and basic mobility (timed up and go test) and completed a demographic questionnaire regarding symptoms in the lower extremities. Activity limitations were measured by the Rheumatoid and Arthritis Outcome Score (RAOS) which examines functional ability, pain, and quality of life. The participants had difficulty with items requiring external rotation of the hips and lower extremity strength. There were moderate correlations between the impairment measures of joint motion, strength, mobility, and activity limitations. Fair correlations were found between the skin scores and the RAOS sections except for pain. The results of this study show that lower extremity involvement is present in persons with SSc. The findings, regarding strength, mobility, and joint motion are related to the ability to perform everyday activities involving the lower extremities, suggest that these areas should be targeted for intervention in persons with SSc.
27193564 Extra-Gastrointestinal Manifestations of Inflammatory Bowel Disease May Be Less Common Tha 2016 Sep BACKGROUND AND AIMS: Extra-intestinal manifestations are well recognized in inflammatory bowel disease (IBD). To what extent the commonly recognized extra-intestinal manifestations seen in IBD patients are attributable to IBD is, however, not clear due to the limited number of controlled studies published. METHODS: We have conducted a study of these manifestations using electronic primary care records. We have identified extra-intestinal manifestations in IBD and non-IBD patients and derived odds ratios (ORs) using conditional logistic regression. RESULTS: A total of 56,097 IBD patients (32.5 % Crohn's disease, 48.3 % ulcerative colitis (UC) and 19.2 % not classified) were matched to 280,382 non-IBD controls. We found records of pyoderma gangrenosum (OR = 29.24), erythema nodosum (OR = 5.95), primary sclerosing cholangitis (OR = 188.25), uveitis (OR = 2.81), ankylosing spondylitis (OR = 7.07), sacroiliitis (OR = 2.79) and non-rheumatoid inflammatory arthritides (OR = 2.66) to be associated with IBD. One or more of these was recorded in 8.1 % of IBD patients and 2.3 % of controls. Non-specific arthritides were present in many more patients, affecting 30 % of IBD patients and 23.8 % of controls overall. We also found weaker associations with a number of conditions not generally considered to be extra-intestinal manifestations including psoriasis, ischemic heart disease, multiple sclerosis and hay fever. CONCLUSION: Although "classical" extra-intestinal manifestations are strongly associated with IBD, most IBD patients remain unaffected. Arthropathies, perceived to be the commonest extra-intestinal manifestation, are not strongly associated with IBD, and the proportion of arthropathies attributable to IBD is likely to be small.
26015614 Locking plate versus retrograde intramedullary nail fixation for tibiotalocalcaneal arthro 2015 Mar BACKGROUND: Tibiotalocalcaneal arthrodesis (TTCA) surgery is indicated for the end-stage disease of the tibiotalar and subtalar joints. Although different fixation technique of TTCA has been proposed to achieve high fusion rate and low complication rate, there is still no consensus upon this point. The purpose of this study is to compare the clinical efficacy of retrograde intramedullary nail fixation (RINF) and locking plate fixation (LPF) for TTCA. MATERIALS AND METHODS: Fifty four patients who underwent TTCA through the lateral approach with lateral fibular osteotomy using RINF (32 patients, 18 male/14 female, mean age: 48) or LPF (22 patients, 12 male/10 female, mean age: 51) between January 2007 and January 2010 were retrospectively analyzed. Demographic and clinical characteristics, surgery (operation time, blood loss) outcomes (postoperative fusion rates, visual analog scale and foot and ankle surgery score and complications) were compared. RESULTS: The LPF group had a shorter operation time (72.3 ± 9.2 vs. 102.8 ± 11.1 min, P < 0.001), less blood loss (75.9 ± 20.2 vs. 140.0 ± 23.8 ml, P < 0.001) and less intraoperative fluoroscopy sessions (3.6 ± 0.9 vs. 8.4 ± 1.3, P < 0.001) than the RINF group. Patients were followed up for 12-24 months (mean of 16.2 months). Both groups had similar postoperative fusion rates (90.6% and 95.4%) and the LPF group showed a nonsignificant lower complication rate (18.2% vs. 28.1% respectively). Patients at higher risk on nonunion due to rheumatoid diseases may have a lower nonunion rate with LPF than RINF (one out of eight vs. three out of nine, P < 0.001). CONCLUSIONS: The LPF for TTCA was simpler to perform compared with RINF, but with similar postoperative outcomes and complication rates.
26438211 Microbial Nucleic Acid Sensing in Oral and Systemic Diseases. 2016 Jan One challenge in studying chronic infectious and inflammatory disorders is understanding how host pattern recognition receptors (PRRs), specifically toll-like receptors (TLRs), sense and respond to pathogen- or damage-associated molecular patterns, their communication with each other and different components of the immune system, and their role in propagating inflammatory stages of disease. The discovery of innate immune activation through nucleic acid recognition by intracellular PRRs such as endosomal TLRs (TLR3, TLR7, TLR8, and TLR9) and cytoplasmic proteins (absent in melanoma 2 and DNA-dependent activator of interferon regulatory factor) opened a new paradigm: Nucleic acid sensing is now implicated in multiple immune and inflammatory conditions (e.g., atherosclerosis, cancer), viral (e.g., human papillomavirus, herpes virus) and bacterial (e.g., Helicobacter pylori, pneumonia) diseases, and autoimmune disorders (e.g., systemic lupus erythematosus, rheumatoid arthritis). Clinical investigations reveal the overexpression of specific nucleic acid sensors in diseased tissues. In vivo animal models show enhanced disease progression associated with receptor activation. The involvement of nucleic acid sensors in various systemic conditions is further supported by studies reporting receptor knockout mice being either protected from or prone to disease. TLR9-mediated inflammation is also implicated in periodontal diseases. Considering that persistent inflammation in the oral cavity is associated with systemic diseases and that oral microbial DNA is isolated at distal sites, nucleic acid sensing may potentially be a link between oral and systemic diseases. In this review, we discuss recent advances in how intracellular PRRs respond to microbial nucleic acids and emerging views on the role of nucleic acid sensors in various systemic diseases. We also highlight new information on the role of intracellular PRRs in the pathogenesis of oral diseases including periodontitis and oral cavity cancer, which might offer future possibilities for disease prevention and therapy.
27984037 Induction of Alternative Proinflammatory Cytokines Accounts for Sustained Psoriasiform Ski 2017 Mar IL-6 inhibition has been unsuccessful in treating psoriasis, despite high levels of tissue and serum IL-6 in patients. In addition, de novo psoriasis onset has been reported after IL-6 blockade in patients with rheumatoid arthritis. To explore mechanisms underlying these clinical observations, we backcrossed an established psoriasiform mouse model (IL-17C+ mice) with IL-6-deficient mice (IL-17C+KO) and examined the cutaneous phenotype. IL-17C+KO mice initially exhibited decreased skin inflammation; however, this decrease was transient and reversed rapidly, concomitant with increases in skin Tnf, Il36α/β/γ, Il24, Epgn, and S100a8/a9 to levels higher than those found in IL-17C+ mice. A comparison of IL-17C+ and IL-17C+KO mouse skin transcriptomes with that of human psoriasis skin revealed significant correlation among transcripts of skin of patients with psoriasis and IL-17C+KO mouse skin, and confirmed an exacerbation of the inflammatory signature in IL-17C+KO mice that aligns closely with human psoriasis. Transcriptional analyses of IL-17C+ and IL-17C+KO primary keratinocytes confirmed increased expression of proinflammatory molecules, suggesting that in the absence of IL-6, keratinocytes increase production of numerous additional proinflammatory cytokines. These preclinical findings may provide insight into why patients with arthritis being treated with IL-6 inhibitors develop new onset psoriasis and why IL-6 blockade for the treatment of psoriasis has not been clinically effective.