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ID PMID Title PublicationDate abstract
22208652 Autoantibodies and Sjögren's syndrome: a physiologist's perspective. 2012 Aug Sjögren's syndrome is a systemic autoimmune condition centred around salivary gland dysfunction and atrophy. There are a plethora of antibodies that mark the decline of the salivary glands, most of which relate to apoptopic mediated destruction of acinar cells. The best known of these autoantibodies, anti-Ro and anti-La form part of the diagnostic criteria for the condition. An emerging viewpoint in recent years is that glandular dysfunction precedes rather than follows glandular atrophy and attention has shifted to the interface between the immune system and the secretory process. An autoantibody against the muscarinic type 3 acetylcholine receptor occupies precisely this position because it inhibits the acetylcholine receptor which controls salivary and lacrimal fluid secretion. The consequence of identifying an autoantibody that can cause rather than simply reflect the disease process are manifold and could have a huge impact on development of therapeutic treatments. Furthermore, a "functional" autoantibody directed against an important component of the autonomic nervous system could also account for some of the extraglandular features of Sjögren's syndrome.
22052658 Validation of potential classification criteria for systemic sclerosis. 2012 Mar OBJECTIVE: Classification criteria for systemic sclerosis (SSc; scleroderma) are being updated jointly by the American College of Rheumatology and European League Against Rheumatism. Potential items for classification were reduced to 23 using Delphi and nominal group techniques. We evaluated the face, discriminant, and construct validity of the items to be further studied as potential criteria. METHODS: Face validity was evaluated using the frequency of items in patients sampled from the Canadian Scleroderma Research Group, 1000 Faces of Lupus, and the Pittsburgh, Toronto, Madrid, and Berlin connective tissue disease (CTD) databases. Patients with SSc (n = 783) were compared to 1,071 patients with diseases similar to SSc (mimickers): systemic lupus erythematosus (n = 499), myositis (n = 171), Sjögren's syndrome (n = 95), Raynaud's phenomenon (RP; n = 228), mixed CTD (n = 29), and idiopathic pulmonary arterial hypertension (PAH; n = 49). Discriminant validity was evaluated using odds ratios (ORs). For construct validity, empirical ranking was compared to expert ranking. RESULTS: Compared to mimickers, patients with SSc were more likely to have skin thickening (OR 427); telangiectasias (OR 91); anti-RNA polymerase III antibody (OR 75); puffy fingers (OR 35); finger flexion contractures (OR 29); tendon/bursal friction rubs (OR 27); anti-topoisomerase I antibody (OR 25); RP (OR 24); fingertip ulcers/pitting scars (OR 19); anticentromere antibody (OR 14); abnormal nailfold capillaries (OR 10); gastroesophageal reflux disease symptoms (OR 8); antinuclear antibody, calcinosis, dysphagia, and esophageal dilation (all OR 6); interstitial lung disease/pulmonary fibrosis (OR 5); and anti-PM-Scl antibody (OR 2). Reduced carbon monoxide diffusing capacity, PAH, and reduced forced vital capacity had ORs of <2. Renal crisis and digital pulp loss/acroosteolysis did not occur in SSc mimickers (OR not estimated). Empirical and expert ranking were correlated (Spearman's ρ = 0.53, P = 0.01). CONCLUSION: The candidate items have good face, discriminant, and construct validity. Further item reduction will be evaluated in prospective SSc and mimicker cases.
21480758 Suppression of inflammatory responses after onset of collagen-induced arthritis in mice by 2011 Dec Rheumatoid arthritis (RA) is closely related to the pathogenesis of tumor necrosis factor α in lesions. We investigated the suppressive effects of a Citrus flavanone naringin on inflammatory responses in mice with collagen-induced arthritis (CIA), a mouse model for RA. To investigate potential preventive and therapeutic effects of naringin, mice were given naringin orally three times a week from the second immunization with collagen (day 21) and from day 31, when symptoms of CIA had reached a plateau, respectively. In both cases, inflammation-related clinical scores for knee joints were significantly reduced by administration of naringin. Histological analyses demonstrated that representative phenomena, such as damage to interchondral joints, infiltration of inflammatory cells and pannus formation, were significantly depressed by treatment with naringin. In addition, increases in the expression of high-mobility group box-1 protein in the joints of mice with CIA were suppressed by naringin. These results suggest that oral administration of naringin might be effective for treating human patients with RA.
22837018 Periodic fever as the manifestation of primary Sjogren's syndrome: a case report and liter 2012 Oct A 56-year-old male had periodic fever for 5 years and suffered from auditory hallucination and hearing impairment for 3 years. Xerostomia, xerophthalmia, elevated anti-SSA/Ro tilter, positive Schirmer's test, and lymphocyte infiltrate of mucoserous gland in lip biopsy of this case confirmed the diagnosis of primary Sjogren's syndrome (pSS). We review literature for fever and neuropsychiatric involvement in pSS case series. Though fever is present in 6-41 % pSS cases, periodic fever has not been reported. Auditory hallucination was rare in cases with pSS. The literature review alerts clinicians that fever and neurological manifestations were not uncommon in pSS cases.
22341206 Rituximab in central nervous system manifestations of patients with primary Sjögren's syn 2012 Mar OBJECTIVES: To evaluate the efficacy of rituximab in central nervous system (CNS) manifestations of patients with primary Sjögren's syndrome (pSS). METHODS: Prospective data from patients with pSS and CNS involvement included in the French AutoImmunity and Rituximab registry were analysed. All patients had diffuse white matter T2-weigted hypersignals. Neurological response was defined as improvement or disappearance of neurological signs. RESULTS: Eleven patients (mean age 55 years [38-77]) were treated with rituximab for their neurological involvement. The mean duration of pSS was 9 years (4-24). Mean baseline ESSDAI score was 17 (5-25). Neurological features were progressive multiple sclerosis-like manifestations (n=6), transverse myelitis (n=1), anxiety and depression disorder (n=1) and cognitive dysfunction (n=3). Mean Expanded Disability Status Score (EDSS) before rituximab was 4 (3-5.5). The mean follow-up was of 13 months (6-58). No neurological change occurred in all 6 patients with multiple sclerosis-like symptoms, in 2/3 patients with cognitive dysfunction or in the patient with anxiety-depression. One patient with depression and cognitive dysfunction disclosed subjective improvement. One patient with transverse myelitis, refractory to cyclophosphamide had an improvement of his walk perimeter (160 meters vs. 116). Mean EDSS score and ESSDAI remained stable. CONCLUSIONS: Rituximab does not seem to be effective in progressive multiple sclerosis-like manifestations of patients with pSS-related CNS involvement.
21337320 Whole stimulated salivary flow: correlation with the pathology of inflammation and damage 2011 Jul OBJECTIVE: To determine which measure of the salivary flow rate, stimulated or unstimulated, is most strongly associated with pathologic changes in minor salivary gland (MSG) biopsy specimens, and to explore the correlation of salivary flow with oral surface damage, disease duration, and symptom severity in patients with primary Sjögren's syndrome (SS). METHODS: In all patients (n = 32), a biopsy of the MSG was performed, and stimulated salivary flow was assessed. Beginning in 2002, unstimulated salivary flow was also assessed. Scores for the severity of symptoms, according to the decayed/missing/filled teeth (DMF) index, were recorded. Associations between measures of salivary flow and covariates characterizing pathology were examined. RESULTS: A definite association between stimulated salivary flow and the MSG focus score, the grade of MSG fibrosis, the duration of dry mouth symptoms, and the DMF score was observed. In contrast, unstimulated salivary flow was not associated with fibrosis, atrophy, the DMF score, or the duration of dry mouth symptoms. In patients with primary SS, the DMF score was associated with pathologic changes in the MSG. Among patients with sicca, 57.9% had an abnormal unstimulated salivary flow rate (versus 82.4% of patients with primary SS), and 15.2% had an abnormal stimulated salivary flow rate (versus 61.8% of patients with primary SS). Among patients with sicca, neither stimulated salivary flow nor unstimulated salivary flow was associated with the degree of fibrosis or atrophy or with the DMF score. CONCLUSION: Compared with unstimulated salivary flow, stimulated salivary flow appeared to be a better measure of inflammation (according to the focus score) and fibrosis. In patients with sicca, the unstimulated salivary flow rate appeared to be abnormal more commonly compared with the stimulated salivary flow rate. In the future, stimulated salivary flow may serve as a noninvasive surrogate biomarker of inflammation and fibrosis as well as a measure of response to treatment in patients with primary SS.
23253241 Adult onset Still's disease: experience from a tertiary care rheumatology unit. 2012 Dec BACKGROUND: Adult-onset Still's disease (AOSD) is a rare chronic inflammatory disorder presenting with prolonged fever and polyarthritis. METHODS: Retrospective study of patients with AOSD, seen between 1992 and 2009 at a large tertiary care hospital. RESULTS: Twenty-nine patients (18 female) with median age at onset of 28 (17-58) years were seen. The clinical features included fever in 29, inflammatory polyarthritis in 26, sore throat in eight and typical rash in 13. Lymphadenopathy was present in 15, hepatomegaly in 15, splenomegaly in 13 and serositis in five patients. Anemia was present in 22, neutrophilic leukocytosis in 28 and thrombocytosis in 13 patients. Acute phase reactants were elevated in all. Fifteen patients had transaminitis. Low titer antinuclear antibodies were present in 6/28 patients. On median follow-up (25 patients) of 23.7 months (range: 3-84) one patient had self-limited or monocyclic pattern, eight had polycyclic and 16 had chronic articular pattern. All patients received non-steroidal anti-inflammatory drugs and 25 received methotrexate and/or prednisolone. During the course 14 patients had remission and of these six were in remission on drugs at last follow-up. One patient received tociliziumab and was in clinical remission. One patient developed macrophage activation syndrome and one had atlanto-axial dislocation. Three patients developed tuberculosis and two died of infection associated with immunosuppression. CONCLUSION: AOSD is an uncommon disorder with 1-2 patients seen at a large tertiary care rheumatology unit. Overall AOSD has a fair outcome with significant morbidity and most needing long-term therapy with steroids and methotrexate.
23009763 Saliva as an ideal milieu for emerging diagnostic approaches in primary Sjögren's syndrom 2012 Sep This review will summarise the state of the art of salivary diagnostics in primary Sjögren's syndrome exploring the potential usefulness of both traditional and emerging biotechnologies for primary Sjögren's syndrome non-invasive and early detection.
22318209 Peripheral neuropathies in Sjögren's syndrome: a critical update on clinical features and 2012 Aug Sjögren's syndrome is a systemic autoimmune disease that, apart from exocrine glands, may affect every organ or system. Involvement of different sections of the peripheral nervous system results in a wide spectrum of neuropathic manifestations. Based on distinct clinical, electrophysiological and histological criteria, the types of neuropathies seen in Sjögren's syndrome include: a) pure sensory which presents with distal symmetric sensory loss due to axonal degeneration of sensory fibers; sensory ataxia due to loss of proprioceptive large fibers (ganglionopathy); or with painful dysethesias (small fiber sensory neuropathy) due to degeneration of cutaneous axons. The latter appears to be the most common neuropathy in Sjögren's syndrome and requires skin biopsy for diagnosis to document loss or reduction of nerve fiber density; b) sensorimotor polyneuropathy affecting sensory and motor axons, often associated with severe systemic or pro-lymhomatous manifestations, such as palpable purpura and cryoglobulinemia, and c) rare types that include autoimmune demyelinating neuropathy, mononeuropathy, mononeuropathy multiplex and autonomic neuropathy. In this review, the frequency, prevalence and diagnostic criteria for each neuropathy subset are discussed and possible pathogenetic mechanisms are outlined.
22875342 Norisoboldine, an alkaloid compound isolated from Radix Linderae, inhibits synovial angiog 2012 Aug Synovial angiogenesis is well recognized as participating in the pathogenesis of rheumatoid arthritis (RA) and has been regarded as a potential target for RA therapy. Previously, we have shown that norisoboldine (NOR) can protect joints from destruction in mice with collagen II-induced arthritis (CIA). Here, we investigate the effect of NOR on synovial angiogenesis in adjuvant-induced arthritis (AA) rats, and clarify the mechanisms in vitro. NOR, administered orally, significantly reduced the number of blood vessels and expression of growth factors in the synovium of AA rats. In vitro, it markedly prevented the migration and sprouting of endothelial cells. Notably, the endothelial tip cell phenotype, which is essential for the migration of endothelial cells and subsequent angiogenesis, was significantly inhibited by NOR. This inhibitory effect was attenuated by pretreatment with N-{N-[2-(3,5-difluorophenyl) acetyl]-(S)-alanyl}-(S)-phenylglycine tert-butyl ester, a Notch1 inhibitor, suggesting that the action of NOR was related to the Notch1 pathway. A molecular docking study further confirmed that NOR was able to promote Notch1 activation by binding the Notch1 transcription complex. In conclusion, NOR was able to prevent synovial angiogenesis in AA rats, which is a putatively new mechanism responsible for its anti-rheumatoid effect. The anti-angiogenesis action of NOR was likely achieved by moderating the Notch1 pathway-related endothelial tip cell phenotype with a potential action target of the Notch1 transcription complex.
22223222 [International clinical practice guidelines and management of rheumatology in Madagascar]. 2012 Feb Developed countries issue recommendations regarding healthcare that aren't constantly appropriate for emergent countries. We suggest some remarks concerning rheumatology in Madagascar, taking account of scientific data, medical ethics, equality and equity. We have studied the minimal cost of care of medical conditions found in our hospital department if we were to follow international recommendations for their management. Then, we have estimated treatment expenses as a percentage of the SMIC (Malagasy minimum monthly salary). Out of 517 patients examined yearly, we have found 62.8% osteoarthritis cases, 6.3% rheumatoid arthritis (RA), and 4,2% septic arthritis. Therefore, the first month of treatment for an arthritis of the knee would absorb 147.3% of the SMIC; diagnosis and treatment of a case of septic arthritis would take up 1762.8% of the minimum wage, and a case of RA without biotherapy would require 175%. According to the American College of Rheumatology criteria which are used as a reference, the treatment of an arthritis of the knee would take only 23% of the SMIC. Caring for septic arthritis would demand 57.5% of the SMIC and while it would yield more arguments for diagnosis such as clinical examination, CRP, and Gram coloration on joint liquid aspiration. We can proceed to RA diagnosis with an acceptable security through precise clinical examination, blood cell count, ESR, CRP, rheumatoid factor and radiography. This means 56% of the SMIC. From this 517 patients, our suggestions would reduce the expense by 35,850% of the SMIC per year. The allocation of such funds onto the treatment of complicated forms of rheumatism would be fair. By refining and evaluating these suggestions, we would come up with appropriate recommendations for emergent countries.
22298270 Inflammatory spinal disease in psoriatic arthritis: a report from the GRAPPA 2010 annual m 2012 Feb Diagnosing axial disease in patients with psoriatic arthritis (PsA) has been largely dependent on identifying inflammatory back pain (IBP), which itself has been difficult to define. We review the criteria used to identify IBP in patients with ankylosing spondylitis (AS) and other forms of spondyloarthritis. Recently, the Ankylosing SpondyloArthritis International Society (ASAS) developed a list of clinical and radiographic criteria for identifying IBP in patients with AS. However, it is more difficult to identify IBP in patients with PsA because generally they have less pain than patients with rheumatoid arthritis or AS. Further, PsA patients may have clinical symptoms of pain but negative radiographs. It may be more useful to identify sacroiliitis or syndesmophytes by magnetic resonance imaging (MRI), since MRI identifies lesions in the sacroiliac joints and the spine much earlier than can be detected on radiographs. In summary, all patients with PsA should be assessed for axial involvement with history, physical examination, and imaging. Patients with psoriasis whose history includes onset of back pain before age 40 years, the presence of night pain, and improvement with exercise but not with rest, or who have limited neck or back mobility, should be referred to a rheumatologist.
27790017 H-2g, a glucose analog of blood group H antigen, mediates monocyte recruitment in vitro an 2012 OBJECTIVE: Monocyte (MN) recruitment is an essential inflammatory component of many autoimmune diseases, including rheumatoid arthritis (RA). In this study we investigated the ability of 2-fucosyllactose (H-2g), a glucose analog of blood group H antigen to induce MN migration in vivo and determined if H-2g-induced interleukin-8 (IL-8/CXCL8) plays a role in MN ingress in RA. METHODS: Sponge granuloma and intravital microscopy assays were performed to examine H-2g-induced in vivo MN migration and rolling, respectively. MNs were stimulated with H-2g, and the production of IL-8/CXCL8 was assessed by enzyme-linked immunosorbent assay and quantitative polymerase chain reaction. Lastly, in vitro MN migration assays and an in vivo RA synovial tissue severe combined immunodeficiency mouse model were used to determine the role of IL-8/CXCL8 in H-2g-induced MN migration. RESULTS: In vivo, H-2g induced significantly greater MN migration compared to phosphate buffered saline. Intravital microscopy revealed that H-2g mediates MN migration in vivo by inducing MN rolling. In addition, H-2g induced MN production of IL-8/CXCL8, a process that was dependent on Src kinase. Moreover, we found that H-2g mediated MN migration in vitro, and in vivo migration was inhibited by a neutralizing anti-IL-8/CXCL8 antibody. CONCLUSION: These findings suggest that H-2g mediates MN recruitment in vitro and in vivo (in part) via IL-8/CXCL8.
21393633 Anti-arthritic effect of E3 ubiquitin ligase, c-MIR, expression in the joints. 2011 Mar Cellular modulator of immune recognition (c-MIR) is an E3 ubiquitin ligase that ubiquitinates MHC class II and CD86 for their endocytosis and subsequent lysosomal degradation. In accordance with their importance in antigen presentation, systemic c-MIR over-expression downmodulates adaptive immune responses. Rheumatoid arthritis (RA) is a chronic synovitis driven by autoimmunity in the joints. Since antigen-presenting cells, such as macrophages, dendritic cells (DCs) and rheumatoid factor-positive B cells are abundant in the rheumatoid synovial tissues, autoantigens released by tissue damage should be presented locally, leading to amplification of systemic arthritogenic immune responses. Assuming that inhibition of the antigen presentation in the synovial tissues should suppress systemic arthritis, we transferred the c-MIR gene to the hind leg synovial tissues from mice with type II collagen (CII)-induced arthritis, an animal model of RA. The gene was transferred adenovirally because adenoviruses can infect DC and macrophages in vivo. Unexpectedly, therapeutic effect was observed only in the treated joints. Splenocyte responses and serum antibodies against CII were not suppressed. Moreover, in vitro studies disclosed that c-MIR gene transfer suppressed IL-6 production from synovial fibroblasts stimulated with tumor necrosis factor (TNF)-α or IL-1β. Bone marrow-derived macrophages and DC from c-MIR transgenic mice were impaired in IL-6 and TNF-α production when stimulated with LPS. This suppression was controlled at the post-transcriptional level since their mRNA was not affected. These results have disclosed a new function of c-MIR, inhibition of inflammatory cytokine production. Induction of c-MIR in the joints could be a new therapeutic approach to the treatment of RA.
21733734 Septic arthritis with negative bacteriological findings in adult native joints: a retrospe 2012 Mar BACKGROUND: No microorganism is identified in 7-35% of cases of septic arthritis. The diagnosis is, therefore, only presumptive. We reviewed our cases of septic arthritis in adult native joints to determine the frequency of negative cultures, disease characteristics and the frequency of misdiagnosis of septic arthritis. METHODS: This retrospective study included all patients admitted to our department from 1979-2005 with arthritis, diagnosed and treated as septic. RESULTS: No microorganism was isolated from synovial fluid or blood samples from 74 out of 398 (19%) patients with presumed septic arthritis. Patients without microorganisms were younger (54 vs 62 years), less likely to have risk factors for septic arthritis (31% vs 41%) and had lower mortality (0 vs 5%) than patients with positive cultures. Long-term outcome was known for 48 patients. A retrospective analysis of all data and long-term outcome concluded that septic arthritis was probable in 18 patients and improbable in 13. Ten of the latter developed rheumatic disease after a mean time of 6 months: rheumatoid arthritis (n=3), spondyloarthropathies (n=3), unclassified rheumatic disease (n=2), Wegener granulomatosis (n=1) and cytosteatonecrosis (n=1). Fever and signs of inflammation were more frequent and synovial fluid cell counts were higher in patients with improbable septic arthritis. Conversely, radiological signs were more common in patients with probable septic arthritis. CONCLUSION: At least 14% of patients diagnosed with septic arthritis with negative bacteriological results subsequently develop rheumatic disease. This pseudoseptic arthritis is indistinguishable from true septic arthritis. When no microorganism is identified, the diagnosis remains presumptive and follow-up is necessary to screen for other diseases, especially rheumatic diseases.
21276901 Metacarpophalangeal joint arthritis. 2011 Feb Arthritis of the metacarpophalangeal joint can result in considerable disability and pain. Inflammatory, posttraumatic, crystalline, and osteoarthritis are common etiologies of joint disease. A variety of nonsurgical treatment options have been shown to be effective, including activity modification, anti-inflammatory medications, splinting, and cortisone injections. In addition, newer generation disease-modifying antirheumatic drugs geared toward the treatment of rheumatoid arthritis have shown promise in retarding the inflammatory process. Another, relatively newer, conservative treatment option includes topical anti-inflammatories such as diclofenac sodium that are now approved by the Federal Drug Administration. Surgical treatment options most commonly include arthroplasty and arthrodesis. In the treatment of thumb metacarpophalangeal arthritis, arthrodesis is a popular and generally reliable surgical solution. In the fingers, arthroplasty remains the most common treatment option. Traditional constrained silicone joint replacements remain the most commonly used. Newer generation, unconstrained, surface replacement arthroplasties have shown promise in the treatment of osteoarthritis and select cases of inflammatory arthritis in which there is good bone stock, no or minimal deformity, adequate supporting soft tissues, and good disease control.
21908949 Effects of flavangenol, an extract of French maritime pine bark on collagen-induced arthri 2011 Flavangenol (FG), an extract of French maritime pine bark (Pinus maritime) mainly contains proanthocyanidin in oligomers. It has many physiological effects, including antioxidant and anti-atherosclerosis. In this study, we evaluated the effects of FG on rat collagen-induced arthritis, a model of human rheumatoid arthritis. The rats were fed with the diet of control, 0.3% FG, or 1% FG for 4 wk after the induction of arthritis. The FG diets, compared with the control diet, suppressed the increase in arthritic score and swelling of the paws in a dose-dependent manner. Histopathological examination revealed evidence that the 1% FG diet suppressed acute and chronic articular lesions in the rats. In addition, the FG diets (0.3% and 1%) suppressed the production of nitric oxide in the plasma of the rats. These results suggest that dietary FG has beneficial effects on collagen-induced arthritis in rats by inhibiting the acute and chronic inflammatory reactions.
21281474 Anti-class a scavenger receptor autoantibodies from systemic lupus erythematosus patients 2011 Jan 31 INTRODUCTION: Inadequate clearance of apoptotic cells by macrophages is one of the reasons for the breakdown of self-tolerance. Class A scavenger receptors, macrophage receptor with collagenous structure (MARCO) and scavenger receptor A (SR-A), which are expressed on macrophages, play important roles in the uptake of apoptotic cells. A previous study reported the presence of the anti-MARCO antibody in lupus-prone mice and systemic lupus erythematosus (SLE) patients. The purpose of this study was to investigate the prevalence of anti-class A scavenger receptor antibodies in patients with various autoimmune diseases, in particular SLE, and the functional implication of those autoantibodies in the phagocytic clearance of apoptotic cells by macrophages. METHODS: Purified recombinant scavenger receptor cysteine-rich (SRCR) polypeptide (ligand-binding domain of MARCO) and recombinant SR-A were used as antigens. By using enzyme-linked immunosorbent assay, the anti-SRCR and anti-SR-A antibodies were detected in the sera of untreated patients with SLE (n = 65), rheumatoid arthritis (n = 65), primary Sjögren syndrome (n = 25), and healthy blood donors (n = 85). The effect of IgG purified from SLE patients or healthy controls on the phagocytosis of apoptotic cells by macrophages was measured by the flow cytometry assay. RESULTS: Anti-SRCR antibodies were present in patients with SLE (18.5%) and rheumatoid arthritis (3.1%), but not in those with primary Sjögren syndrome. Anti-SR-A antibodies were present in patients with SLE (33.8%), rheumatoid arthritis (13.8%), and primary Sjögren syndrome (12.0%). IgG from SLE patients positive for anti-SRCR or anti-SR-A antibodies showed a higher inhibition rate on binding of apoptotic cells to macrophages than IgG from healthy controls (both P < 0.05). IgG from SLE patients positive for both anti-SRCR and anti-SR-A antibodies showed a significantly higher inhibition rate on ingestion of apoptotic by macrophages than IgG from healthy controls (P < 0.05). CONCLUSIONS: Our results indicated that autoantibodies to class A scavenger receptors might contribute to the breakdown of self-tolerance by impairing the clearance of apoptotic debris and play a role in the pathogenesis of autoimmune disease, especially in SLE.
22568661 The diagnostic significance of Fourier-domain optical coherence tomography in Sjögren syn 2012 Aug PURPOSE: To determine the role of Fourier-domain optical coherence tomography (FD-OCT) in tear meniscus imaging and evaluate its diagnostic significance in Sjögren syndrome (SS), non-Sjögren's aqueous tear deficiency (ATD) and lipid tear deficiency (LTD) patients. METHODS: Two hundred and thirty-six dry eye patients and 174 healthy controls were enrolled in this study. All subjects were grouped as follows: group A (ATD), group B (LTD), group C (SS) and group D (normal controls). All subjects underwent dry eye questionnaire, FD-OCT scanning, tear film break-up time (BUT), corneal fluorescence staining and Schirmer I test (SIT). Tear meniscus height (TMH), tear meniscus depth (TMD) and tear meniscus cross-sectional area (TMA) were measured using FD-OCT (RTVue-100). The area under the receiver operating characteristic curve and the cut-off point were determined using a logistic regression model. RESULTS: Mean TMH, TMD, TMA, BUT and SIT of dry eye patients were significantly lower than those of the controls (p < 0.05). Tear meniscus values were significantly decreased in patients with SS compared with ATD and LTD patients. Tear meniscus values were significantly correlated with clinical examination results in all groups. Accuracy of dry eye diagnosis by FD-OCT is highest in patients with SS and lowest in LTD patients. The clinical diagnostic critical points were quite different between groups. CONCLUSIONS: Fourier-domain optical coherence tomography could provide precise measurement of the tear meniscus with favourable repeatability. Diagnostic significance is more conspicuous in patients with SS. Tear meniscus measurement by FD-OCT is expected to become a valuable technique in ATD dry eye screening and diagnosis.
21554873 Development of non-antibiotic macrolide that corrects inflammation-driven immune dysfuncti 2011 Aug 31 Inflammation-driven immune dysfunction supports the development of several chronic human disorders including inflammatory bowel diseases and rheumatoid arthritis. Macrolides are effective antibiotics endowed with immunomodulatory effects. In this study we report the chemical synthesis and the pharmacological characterization of CSY0073, a non-antibiotic derivative of azithromycin. CSY0073 was tested for efficacy in two experimental models of colitis induced by administering mice with dextran sulfate (DSS) and trinitrobenzene sulphonic acid (TNBS) and in collagen induced arthritis. Like azithromycin, CSY0073 improved clinical, macroscopic and histopathological scores in mice administered DSS (12.5μmol/kg/day p.o.) and TNBS (45μmol/kg/day p.o.). When administered to TNBS-treated mice, CSY0073 effectively attenuated influx of neutrophils and macrophages into the colonic mucosa and reduced the intestinal expression pro-inflammatory cytokines TNFα, IL-2 and IFNγ. CSY0073 (0.1 to 10μM) counter-regulated TNFα, IFNγ, IL-12 and IL-23 release caused by exposure of mouse spleen monocytes and CD11b+ cells isolated from the colonic lamina propria to endotoxin. CSY0073 (25μmol/kg/day) reduced clinical scores in the collagen induced murine model of rheumatoid arthritis. In myeloid cells, CSY0073 (10μM) prevented the nuclear translocation of the p65 subunit of NF-κB and its binding to canonical NF-κB responsive elements. In summary, we report a novel class of non-antibiotic 14-member macrocycles with anti-inflammatory and immune-modulatory effects. CSY0073, the prototype of this new class of macrolides exerts counter-regulatory activity on NF-κB signaling. This study suggests the exploitation of non-antibiotic macrolides in the treatment of inflammatory disorders characterized by immune dysfunction.