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ID PMID Title PublicationDate abstract
20558268 Effects of compounds from bi-qi capsule on the expression of inflammatory mediators in lip 2011 Jul 14 AIM OF THE STUDY: The Bi-Qi Capsule (Bi-Qi) has been used in clinic as prescribed drug for the treatment of rheumatic arthritis, rheumatoid arthritis and other osteoarticular diseases about 20 years in China. Pharmacological and clinical studies have confirmed the anti-inflammatory and analgesic action of Bi-Qi in vivo. However, its anti-inflammatory molecular mechanism is still unclear. The objective of the study is to reveal the anti-inflammatory molecular mechanism of Bi-Qi which would form an additional proof to the traditional experience of Bi-Qi in clinical administration. MATERIALS AND METHODS: The aqueous extract of Bi-Qi was used to evaluate the anti-inflammatory action in murine macrophage cell line RAW 264.7 treated with lipopolysaccharide (LPS). Cell viability was evaluated by MTT assay. Production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)) were measured by the Griess colorimetric method and enzyme-linked immunosorbent assay (ELISA), respectively. Protein expression levels of cyclooxygenase 2 (COX-2) were monitored by cell-based ELISA. Proteome profiler array was analyzed to evaluate 40 cytokines at protein level. In addition, interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α) synthesis were analyzed using ELISA to confirm the result of the Proteome profiler array. The gene expression levels of inducible nitric oxide synthase (iNOS), COX-2, TNF-α, IL-6, and interleukin 1β (IL-1β) were detected by quantitative real-time reverse-transcription polymerase chain reaction (real-time RT-PCR). RESULTS: Bi-Qi significantly decreased the production of NO, PGE(2), and inhibited the protein expression of COX-2. The Proteome profiler array showed that eight protein cytokines were down-regulated and six protein cytokines were up-regulated by Bi-Qi. Furthermore, the results of TNF-α and IL-6 protein expression analyzed by ELISA were similar to those of Proteome profiler array. The results of real-time RT-PCR demonstrated that iNOS, COX-2, TNF-α, IL-6 and IL-1β gene expression were also significantly reduced by Bi-Qi. CONCLUSION: These results suggested that the anti-inflammatory molecular mechanism of Bi-Qi might be the results from modulating the LPS-mediated NO-iNOS pathway, COX-2 pathway via inhibition of iNOS, COX-2, TNF-α, IL-6 and IL-1β expression in activated macrophages. In addition, these results provided evidence to understand the therapeutic effects of Bi-Qi on various inflammatory diseases, e.g. rheumatoid arthritis, rheumatic arthritis and other osteoarticular diseases.
21128258 Abatacept in the treatment of patients with psoriatic arthritis: results of a six-month, m 2011 Apr OBJECTIVE: To assess the safety and efficacy of abatacept, a selective T cell costimulation modulator, in patients with psoriatic arthritis (PsA). METHODS: In this 6-month, multicenter, randomized, double-blind, placebo-controlled, phase II study, 170 PsA patients with a psoriasis target lesion (TL) ≥2 cm who had previously taken disease-modifying antirheumatic drugs (DMARDs), including anti-tumor necrosis factor (anti-TNF) agents, were randomized (1:1:1:1) to receive placebo or abatacept at doses of 3 mg/kg, 10 mg/kg, or 30/10 mg/kg (2 initial doses of 30 mg/kg, followed by 10 mg/kg) on days 1, 15, and 29 and then once every 28 days thereafter. The primary end point was the American College of Rheumatology 20% criteria for improvement (ACR20 response) on day 169. Other key end points were magnetic resonance imaging (MRI) scores for joint erosion, osteitis, and synovitis, scores on the Health Assessment Questionnaire (HAQ) and the Short Form-36 (SF-36) health survey, the investigator's global assessment of psoriasis, the TL score, and the Psoriasis Area and Severity Index (PASI) score. RESULTS: Proportions of patients achieving an ACR20 response were 19%, 33%, 48%, and 42% in the placebo, the abatacept 3 mg/kg, the abatacept 10 mg/kg, and the abatacept 30/10 mg/kg groups, respectively. Compared with placebo, improvements were significantly higher for the abatacept 10 mg/kg (P = 0.006) and 30/10 mg/kg (P = 0.022) groups, but not for 3 mg/kg group (P = 0.121). All abatacept regimens resulted in improved MRI, HAQ, and SF-36 scores, with 10 mg/kg showing the greatest improvements. Improvements in the TL and PASI scores were observed in all abatacept arms; a response according to the investigator's global assessment was seen only with 3 mg/kg of abatacept. The safety profiles were similar among the treatment arms. CONCLUSION: The results of this study suggest that 10 mg/kg of abatacept, the approved dosage for rheumatoid arthritis and juvenile idiopathic arthritis, may be an effective treatment option for PsA.
22273003 Treatment with Selemax®, a selenium-enriched yeast, ameliorates experimental arthritis in 2012 Nov 28 Rheumatoid arthritis (RA) is a chronic inflammatory disease that mainly targets the synovial membrane, cartilage and bone. It affects 1 % of the population and is associated with significant morbidity and increased mortality. Se is an essential trace element with antioxidant properties and the ability to modulate the immune responses. Selemax® is an inactive yeast (Saccharomyces cerevisiae) enriched with organic Se. The aim of the present study was to investigate the effects of Selemax® administration in models of an antigen-induced arthritis (AIA) in C57BL/6 mice, and of an adjuvant-induced arthritis (AdIA) in Holtzman rats. As control, the animals were treated with the same inactivated yeast species that was not enriched for Se. In the AIA model, treatment with different doses of Selemax® (0·01, 0·1, 1 and 10 % added to food) significantly decreased the number of inflammatory cells recruited to the knee cavity, essentially by reducing the number of neutrophils. Levels of proinflammatory cytokines, including TNF-α, IL-1β and chemokine (C-X-C motif) ligand 1/keratinocyte chemoattractant (CXCL1/KC), were also reduced in the peri-articular tissue of mice treated with Selemax® at the tested dose (1 %). In the AdIA model in rats, Selemax® treatment decreased paw oedema and hypernociception. This reduction was associated with inhibition of the influx of proinflammatory cells. Therefore, treatment with Selemax® is associated with amelioration of several inflammatory and functional parameters in models of arthritis, suggesting that this Se-enriched yeast should be evaluated further in patients with RA.
21584942 Phase II study of tofacitinib (CP-690,550) combined with methotrexate in patients with rhe 2011 Aug OBJECTIVE: To compare the efficacy, safety, and tolerability of 4 doses of oral tofacitinib (CP-690,550) with placebo in Japanese patients with active rheumatoid arthritis (RA) receiving stable background methotrexate (MTX) who had an inadequate response to MTX alone. METHODS: A total of 140 patients were randomized to receive tofacitinib 1, 3, 5, and 10 mg twice a day or placebo in this 12-week, phase II, double-blind study. All patients remained on background MTX. Efficacy and safety were assessed at weeks 1, 2, 4, 8, and 12. The primary efficacy end point was the American College of Rheumatology 20% improvement criteria (ACR20) response rate at week 12. RESULTS: ACR20 response rates at week 12 were significant (P < 0.0001) for all tofacitinib treatment groups: 1 mg twice a day, 64.3%; 3 mg twice a day, 77.8%; 5 mg twice a day, 96.3%; and 10 mg twice a day, 80.8% versus placebo, 14.3%. A significant dose-response relationship for the ACR20 was observed (P < 0.0001). Low disease activity was achieved by 72.7% of patients with high baseline disease activity for tofacitinib 10 mg twice a day at week 12 (P < 0.0001). Significant improvements in the ACR50, ACR70, Health Assessment Questionnaire Disability Index, and Disease Activity Score 28-3 (C-reactive protein) were also reported. The most commonly reported adverse events (AEs) were nasopharyngitis (n = 13) and increased alanine aminotransferase (n = 12) and aspartate aminotransferase (n = 9) levels. These AEs were mild or moderate in severity. Serious AEs were reported by 5 patients. No deaths occurred. CONCLUSION: In Japanese patients with active RA with an inadequate response to MTX, tofacitinib in combination with MTX over 12 weeks was efficacious and had a manageable safety profile.
22981300 Atypical forms of optic neuritis. 2012 Oct Inflammatory optic neuritis (ON) represents a frequent clinical situation in neurology and ophthalmology. The most current etiology is multiple sclerosis (MS) but, when MRI and Cerebrospinal fluid (CSF) analyses are normal, ON is usually considered as "idiopathic" with a suspected viral etiology. In rare cases, a systemic disease such as sarcoidosis, lupus or Sjögren syndrome may be diagnosed. In several cases either a recurrence or a myelitis may occur without any argument for MS. In the first case, it corresponds to relapsing inflammatory optic neuritis (RION) and in the second case to neuromyelitis optica (NMO). In the present paper, the author successively presents the various clinical situations and complementary findings (infectious, vasculitis, NMO or idiopathic) that can lead to a differential diagnosis of MS in a context of ON.
22733368 Correlations between histopathologic and scintigraphic parameters of salivary glands in pa 2012 Sep The aim of this study is to evaluate the diagnostic value of quantifying salivary gland scintigraphy in correlation to the labial biopsy findings of Sjögren's syndrome (SS). Thirty patients suspected of having SS referred to our clinic for salivary gland scintigraphy were included to this study. All patients underwent salivary gland biopsy as well. The severity of histopathologic changes was graded according to the Chisholm and Mason scoring system. Dynamic scintigraphy was performed and region of interests (ROI) were drawn. Time activity curves for salivary glands were generated. Count rates of maximum, minimum activity after lemon juice stimuli, and last minute activities of parotid and submandibular glands were obtained. On the basis of this ROI counts, excretion fraction (EF%) was calculated for all salivary glands. The mean EF% for normal parotid gland and pathologic parotid gland was 54.5 ± 13.9 and 45.8 ± 18.42, respectively, while it was 46.7 ± 11.7 for the normal submandibular gland and 29.3 ± 18.8 for the pathologic submandibular gland. With progression in histopathologic grades from 0 to 4, the EF decreased in all salivary glands. Decreased EF in the salivary glands is correlated with the SS, and salivary gland scintigraphy is a sensitive and valid method for evaluation of the function of the salivary glands.
21910074 Therapeutic effect of Chinese herbal medicine for strengthening qi, nourishing yin, and re 2011 Sep OBJECTIVE: To observe the therapeutic effect of Chinese herbal medicine for strengthening qi, nourishing yin, and removing stasis on serum osteopontin (OPN) and quality of life (QOL) in patients with primary Sjogren's syndrome (pSS) and to study the correlation between OPN level and the disease. METHODS: Sixty-eight pSS patients were randomly assigned to two groups: the treatment group (35 cases) treated by Chinese herbal medicine for strengthening qi, nourishing yin, and removing stasis combined with hydroxychloroquine sulfate tablet (HCQ) and the control group (33 cases) treated by HCQ only. Both were treated for 3 months. Before and after treatment, immunoglobulin G (IgG) level, erythrocyte sedimentation rate (ESR), and OPN level were measured. The QOL in patients was evaluated using the Short Form-36 Health Survey (SF-36) before and after treatment. Thirty healthy females were taken as the normal control. RESULTS: Before treatment, levels of IgG, ESR, and OPN in patients were higher than those in the normal control. After 3 months of treatment, those in both treatment groups decreased but were lower in the treatment group than those in the control group (P<0.05). The scores of 8 dimensions of SF-36 were lower in the pSS patients than those in the normal control (P<0.05) and higher in the treatment group than in the control group after treatment (P<0.05). Furthermore, there was a positive correlation between the levels of OPN and the levels of IgG and ESR, and a negative correlation between OPN levels and the overall score of SF-36 (P<0.05). CONCLUSIONS: Chinese herbal medicine for strengthening qi, nourishing yin, and removing stasis could alleviate pSS disease and improve the QOL. In addition, the OPN level might be used as an evaluating index for pSS disease.
21330342 Chemokine saliva levels in patients with primary Sjögren's syndrome, associated Sjögren' 2011 Jul OBJECTIVE: To assess the saliva levels of CXCL13, CXCL10, CCL2, CCL3, CXCL12 and CCL5 in patients with primary SS (pSS), patients with associated SS (aSS), patients with systemic autoimmune disease (SAD) without SS, pre-clinical SS and healthy controls. METHODS: We included 44 patients with pSS (Group A), 30 with aSS (Group B), 49 with SAD without SS (Group C), 14 patients with SAD and focal lip infiltrates, but who do not fulfil SS criteria (Group D, pre-clinical SS) and 32 healthy controls (Group E). Saliva samples were collected and analysed for chemokine levels by luminometry. We used descriptive statistics and the Mann-Whitney U-test and Kruskall-Wallis test. RESULTS: All the studied chemokines were found at low concentration in controls with the exception of CCL2. Patients with pSS had higher levels CXCL10 and CCL2 than controls (P = 0.05). However, they had similar levels of CXCL13, CCL5, CXCL12, CCL2 and CXCL10 than patients with aSS and SAD without SS. Patients with pre-clinical SS had higher levels of CXCL10 than patients with pSS (P = 0.03), aSS (P = 0.04) and controls (P = 0.001). CCL2 levels were higher in all patients with an autoimmune background when compared with controls (P < 0.05 for each comparison). CONCLUSION: We found no difference in salivary chemokines between patients neither with pSS or aSS nor in patients with SAD. CCL2 and CXCL10 were increased in all patients with an autoimmune background. CXCL10 was notably increased in pre-clinical SS, suggesting it could be an early inflammatory salivary biomarker.
23247725 New autoimmune diseases after cord blood transplantation: a retrospective study of EUROCOR 2013 Feb 7 To describe the incidence, risk factors, and treatment of autoimmune diseases (ADs) occurring after cord blood transplantation (CBT), we analyzed both CBT recipients reported to EUROCORD who had developed at least 1 new AD and those who had not. Fifty-two of 726 reported patients developed at least 1 AD within 212 days (range, 27-4267) after CBT. Cumulative incidence of ADs after CBT was 5.0% +/- 1% at 1 year and 6.6% +/- 1% at 5 years. Patients developing ADs were younger and had more nonmalignant diseases (P < .001). ADs target hematopoietic (autoimmune hemolytic anemia, n = 20; Evans syndrome, n = 9; autoimmune thrombocytopenia, n = 11; and immune neutropenia, n = 1) and other tissues (thyroiditis, n = 3; psoriasis, n = 2; Graves disease, n 1; membranous glomerulonephritis, n = 2; rheumatoid arthritis, n = 1; ulcerative colitis, n = 1; and systemic lupus erythematosus, n = 1). Four patients developed 2 ADs (3 cases of immune thrombocytopenia followed by autoimmune hemolytic anemia and 1 Evans syndrome with rheumatoid arthritis). By multivariate analysis, the main risk factor for developing an AD was nonmalignant disease as an indication for CBT (P = .0001). Hematologic ADs were most often treated with steroids, rituximab, and cyclosporine. With a median follow-up of 26 months (range, 2-91), 6 of 52 patients died as a consequence of ADs. We conclude that CBT may be followed by potentially life-threatening, mainly hematologic ADs.
21279993 The PTPN22 R263Q polymorphism is a risk factor for rheumatoid arthritis in Caucasian case- 2011 Feb OBJECTIVE: Recently, a functional PTPN22 variant (R263Q; rs33996649) was found to be associated with systemic lupus erythematosus (SLE). This study was undertaken to analyze the influence of this polymorphism on the risk of rheumatoid arthritis (RA). METHODS: RA patients (n = 5,579) were recruited from outpatient clinics from 6 different countries (Spain, New Zealand, the UK, Norway, The Netherlands, and Germany). Healthy controls (n = 5,392) were recruited from the same areas. There was 100% power to detect an effect equivalent to that observed in SLE. Samples were genotyped for the PTPN22 R263Q (rs33996649) and PTPN22 R620W (rs2476601) polymorphisms using a TaqMan 5'-allele discrimination assay. The effect of the R263Q variant was analyzed in isolation and in combination with the effect of R620W, using Unphased and Stata 10 software. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined. RESULTS: The minor allele A of PTPN22 R263Q was significantly associated with a lower risk of RA in the pooled analysis of the 6 populations (P = 0.016, Mantel-Haenszel pooled OR 0.80 [95% CI 0.67-0.96]), independent of the effect of the R620W polymorphism. Both polymorphisms had an additive effect. The more RA risk alleles carried (R263Q G allele, R620W T allele), the higher the RA risk (for 2 versus 1 risk allele P = 0.014, OR 1.28 [95% CI 1.05-1.55], for 3 versus 1 risk allele P = 6.67 × 10(-11) , OR 2.01 [1.63-2.48], and for 4 versus 1 risk allele P = 6.50 × 10(-11) , OR 3.55 [2.42-5.20]). CONCLUSION: Our findings indicate that the minor allele of the PTPN22 R263Q polymorphism is associated with a lower risk of RA. This association is independent of the well-established association between PTPN22 R620W and RA. Both polymorphisms have an additive effect on the risk of RA.
21910436 Human tear protein analysis enabled by an alkaline microfluidic homogeneous immunoassay. 2011 Nov 1 The ability to probe the protein content of human tear fluid has enormous potential for deepening our understanding of ocular and systemic disease pathology and enabling novel noninvasive tear-based diagnostic technologies. To overcome current challenges in tear proteomic measurements, we report on the first microfluidic homogeneous immunoassay capable of making rapid, quantitative, and specific measurements of endogenous tear protein biomarkers in human tear fluid. Lactoferrin (Lf) is a tear-specific biomarker for Sjögren's syndrome (SS), a serious systemic autoimmune disease currently diagnosed through rudimentary volumetric and surface chemistry measurements and an invasive lip biopsy. We detail optimization of a homogeneous electrophoretic immunoassay for Lf in <1 μL of tear fluid at clinically relevant concentrations. In particular, we present assay development details and a final assay that enables quantification of Lf in <5 s in a clinically relevant range for SS diagnostics. Characterization suggests the on-chip assay is accurate to within 15% of ELISA, specific (<15% nonspecific signal), and with a lower limit of detection of 3 ± 2 nM Lf in human tear matrix. Additionally, we develop and characterize a protocol for eluting proteins from nitrocellulose Schirmer strips, the clinical de facto standard for tear collection and storage. We relate on-chip measured Lf concentrations back to ocular surface concentrations for the first time to our knowledge. Taken in sum, this work details important steps toward (1) expanding the set of proteins quantified by electrophoretic immunoassays to encompass a wider range of isoelectric points than has been reported, (2) creating a first-in-kind translatable assay with clinical relevance to SS diagnostics, and (3) expanding the analytical toolkit available for rapid tear protein measurements, as is relevant to the advancement of basic research and clinical medicine.
21437616 A case of Sjögren syndrome with pulmonary amyloidosis complicating microscopic polyangiit 2011 Dec We present the case of a 71-year-old Japanese woman with Sjögren syndrome complicated with pulmonary amyloidosis who developed microscopic polyangiitis. She was admitted because of fever, weight loss, and paresthesia of the plantae and fingers. Chest computed tomography revealed bilateral multiple nodules with calcification in the lung. Transbronchial lung biopsy specimens showed AL-type (primary) amyloid deposits. The patient also tested positive for myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA), with changes in the MPO-ANCA titer that paralleled changes in the symptoms. Nerve conduction velocity findings showed mononeuropathy multiplex. Livedo vasculitis was observed on bilateral lower legs, and skin biopsy showed leukoclastic vasculitis. We diagnosed the patient as having microscopic polyangiitis.
23146870 Salivary proteomics in biomedical research. 2013 Jan 16 Proteins that are important indicators of physiological or pathological states, can provide information for the identification of early and differential markers for disease. Saliva, contains an abundance of proteins, offers an easy, inexpensive, safe, and non-invasive approach for disease detection, and possesses a high potential to revolutionize the diagnostics. Discovery of salivary biomarkers could be used to scrutinize health and disease surveillance. The impact of human saliva proteome analysis in the search for clinically relevant disease biomarkers will be realized through advances made using proteomic technologies. The advancements of emerging proteomic techniques have benefited biomarker research to the point where saliva is now recognized as an excellent diagnostic medium for the detection of disease. This review presents an overview of the value of saliva as a credible diagnostic tool and we aim to summarize the proteomic technologies currently used for global analysis of saliva proteins and to elaborate on the application of saliva proteomics to the discovery of disease biomarkers, and discuss some of the critical challenges and perspectives in this field.
22867055 Germinal center kinase-like kinase (GLK/MAP4K3) expression is increased in adult-onset Sti 2012 Aug 6 BACKGROUND: Germinal center kinase-like kinase (GLK, also termed MAP4K3), a member of the MAP4K family, may regulate gene transcription, apoptosis and immune inflammation in response to extracellular signals. The enhanced expression of GLK has been shown to correspond with disease severity in patients with systemic lupus erythematosus. We investigated the role of GLK in the pathogenesis of adult-onset Still's disease, which shares some similar clinical characteristics with systemic lupus erythematosus. METHODS: The frequencies of circulating GLK-expressing T-cells in 24 patients with active adult-onset Still's disease and 12 healthy controls were determined by flow cytometry analysis. The expression levels of GLK proteins and transcripts were evaluated in peripheral blood mononuclear cells by immunoblotting and quantitative PCR. Serum levels of T helper (Th)17-related cytokines, including IL-1β, IL-6, IL-17 and TNF-α, were measured by ELISA. RESULTS: Significantly higher median frequencies of circulating GLK-expressing T-cells were observed in patients with adult-onset Still's disease (31.85%) than in healthy volunteers (8.93%, P <0.001). The relative expression levels of GLK proteins and transcripts were also significantly higher in patients with adult-onset Still's disease (median, 1.74 and 2.35, respectively) compared with those in healthy controls (0.66 and 0.92, respectively, both P <0.001). The disease activity scores were positively correlated with the frequencies of circulating GLK-expressing T-cells (r = 0.599, P <0.005) and the levels of GLK proteins (r = 0.435, P <0.05) or GLK transcripts (r = 0.452, P <0.05) in patients with adult-onset Still's disease. Among the examined Th17-related cytokines, elevated levels of serum IL-6 and IL-17 were positively correlated with the frequencies of circulating GLK-expressing T-cells and the levels of GLK proteins as well as transcripts in patients with adult-onset Still's disease. GLK expression levels decreased significantly after effective therapy in these patients. CONCLUSIONS: Elevated expression levels of GLK and their positive correlation with disease activity in patients with adult-onset Still's disease indicate that GLK may be involved in the pathogenesis and act as a novel activity biomarker of this disease.
22198497 Prognosis and outcome of non-Hodgkin lymphoma in primary Sjögren syndrome. 2012 Jan Sjögren syndrome (SS) has been associated with the development of non-Hodgkin lymphoma (NHL). From a cohort of 584 SS patients followed in our department from 1980 to 2010, we retrospectively analyzed 53 consecutive NHL cases. Considerations included histologic type, clinical manifestation and NHL staging, treatment, response rate and overall survival (OS), event-free survival (EFS), and standardized mortality ratio (SMR).Mucosa-associated lymphoid tissue (MALT) lymphomas constituted the majority (59%) of NHL subtypes, followed by nodal marginal zone lymphomas (NMZLs) (15%) and diffuse large B-cell lymphomas (DLBCLs) (15%). Six lymphoma patients died during the median follow-up of 40.8 months. The corresponding age/sex-adjusted SMR of SS with and without NHLs versus the general population was 3.25 (95% confidence interval [CI] 1.32-6.76) and 1.08 (95% CI, 0.79-1.45), respectively. A "watch and wait" policy was adopted for 9 patients with asymptomatic localized salivary MALT lymphomas. Eight patients with limited-stage MALT lymphomas and extraglandular manifestations were treated with rituximab. Ten MALT lymphoma patients with disseminated disease received chemotherapy with or without rituximab. The 3-year OS and EFS in patients with MALT lymphomas was 97% and 78%, respectively. Rituximab plus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) was the chosen therapeutic intervention for patients with DLBCLs. A successful outcome was recorded for this group, with 100% OS and EFS at 3 years. Patients with NMZLs had a less favorable outcome, with a 3-year OS of 80% and EFS of 53%. Our results describe the course and prognosis of SS-associated NHL and highlight the need for a risk-stratified treatment approach.
22023238 New technologies for studying the complexity of oral diseases. 2012 Mar Several new technologies are providing useful diagnostic tools and new information related to the pathogenesis of certain oral diseases. In this review, we describe several of these technologies including gene and microRNA arrays, proteomics, and antigen arrays as they relate to the study of Sjögren's syndrome and head and neck cancer. A common theme is the systematic analysis of large-scale inventories of RNAs, proteins, and autoantibody biomarkers revealing information not previously recognized. We also discuss metagenomic approaches that characterize the many different microorganisms present in the oral cavity that may impact oral and human health. Lastly, we describe applications of a new type of antibody-profiling technology termed Luciferase Immunoprecipitation Systems (LIPS), which has a wide dynamic range of detection of both linear and conformational epitopes needed for optimum diagnostics and biomarker discovery. We propose that the information offered by these technologies will enhance our ability to diagnose, treat, and further understand the pathogenesis of multiple oral diseases.
22658898 Differential, size-dependent sensory neuron involvement in the painful and ataxic forms of 2012 Aug 15 Primary Sjögren's syndrome (pSS)-associated neuropathy manifests a wide variety of peripheral neuropathies that may show overlap among the neuropathic forms. In this report, we describe histopathological findings of two autopsy cases with pSS-associated neuropathy; one of them manifested the painful form and another showed ataxic form. The population of dorsal root ganglion (DRG) neurons and the density of myelinated fibers in the dorsal spinal root were variably reduced among spinal segments in both forms. In the painful form, there was a prominent reduction of small neurons, while in the ataxic form, large neurons were predominately lost. In accordance with the degree of the DRG cell loss, the modality of nerve fiber loss in the dorsal spinal roots and sural nerve correlated well with the corresponding DRG neuron loss. Prominent CD8+ T lymphocyte infiltration was present in the DRG, sympathetic ganglion, epineurial and perineurial space throughout the peripheral nerve trunks, and visceral organs, including the submandibular gland of both forms. Although the size of affected DRG neurons is different, these two forms share a similar causal mechanism, namely, cytotoxic autoimmunity to ganglion neurons, which may be one of a continuum of etiological factors. This hypothesis may have an impact on therapeutic approach.
22408873 [Treatment of primary Sjögren syndrome]. 2012 Feb Treatment of primary Sjögren's syndrome is adapted to the initial evaluation of symptom and extraglandular manifestation according to the damage/activity ratio. Symptomatic treatment is systematic, whereas systemic treatment is limited to the active extra glandular forms. There is no international treatment consensus. Biologics are currently evaluated.
22160845 Therapeutic response of patients with adult Still's disease to biologic agents: multicente 2012 Sep OBJECTIVE: The efficacy of biologics in treating adult Still's disease (ASD) is suggested, but the information is still lacking and the validation is insufficient. To determine the efficacy of several biologic agents in refractory ASD in Japan, a multicenter survey was performed. METHOD: Clinical data on 16 ASD patients who had been treated with at least 1 of the biological agents (total 24 occasions) were collected retrospectively. RESULTS: Infliximab was used in 9 cases, etanercept in 4, and tocilizumab in 11. Half of the patients that had been treated initially with infliximab or etanercept were changed to another biologics. Tocilizumab was effective in cases switched from another 2 drugs. Tocilizumab showed efficacy in treating both systemic and arthritic symptoms and showed apparent steroid-sparing effect and the highest continuation rate. CONCLUSION: Tocilizumab may be a promising biologic agent in refractory ASD.
21716914 Complete atrioventricular block in adult Sjögren's syndrome with anti-Ro autoantibody. 2011 Jun Anti-Ro autoantibody is associated with Sjögren's syndrome (SS), systemic lupus erythematosus (SLE), and neonatal lupus syndrome (i.e., congenital complete heart block in newborns). Generally, the adult atrioventricular (AV) node is believed to be relatively resistant to the scarring effects of anti-Ro/anti-La autoantibodies. However, there have been some reports of adult complete AV block in SS and SLE patients. Here, we report a case of complete heart block in primary SS with anti-Ro autoantibodies, with no other risk factor for the development of heart block, and review their etiological association.