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ID PMID Title PublicationDate abstract
26646777 Periodontitis prevalence and serum antibody reactivity to periodontal bacteria in primary 2016 Jan AIMS: The aims of this study were as follows: (i) To assess the prevalence of periodontitis among patients with primary Sjögren's syndrome (pSS) and comparator groups of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). (ii) To perform a pilot study to compare serum antibody responses to 10 oral/periodontal bacteria in these patient groups and a historical comparator group of patients with periodontitis. MATERIALS AND METHODS: Standard clinical periodontal assessments were performed on 39 pSS, 36 RA and 23 OA patients and "In-house" antibody ELISAs for serum antibodies against 10 oral/periodontal bacteria were performed in these groups. RESULTS: Forty-six percent of the pSS group, 64% of the RA group and 48% of the OA group had moderate/severe periodontitis. These frequencies did not reach statistical significance between groups. Raised antibody levels to Prevotella denticola were found in the pSS, RA and periodontitis groups compared to the OA group. Significant between group differences were seen for Aggregatibacter actinomycetemcomitans, Prevotella intermedia and Campylobacter showae. None of these differences were specifically associated with pSS. CONCLUSION: This study showed no increase in periodontitis in pSS patients. Although the P. denticola data are of interest, identifying bacterial triggering factors for pSS will likely require alternative strategies including modern techniques such as microbiome analysis.
26482506 Do IgA antibodies to Chlamydia trachomatis have protective role in humoral immunity: a stu 2015 Nov Chlamydia trachomatis-induced genitourinary Reactive Arthritis (ReA) can serve as good model for host-pathogen interaction. However, due to poor antigen presentation, cell-mediated immunity does not contribute as anticipated. Present study aims to evaluate protective role of anti-C. trachomatis antibodies vis-a-vis inflammatory chlamydial Major Outer Membrane Protein (MOMP). Prospective study was undertaken in 30 patients with genitourinary ReA. 30 Rheumatoid Arthritis (RA) and 30 osteoarthritis patients constituted controls. Subjects found to be PCR-positive for C. trachomatis were investigated for presence of MOMP in Synovial Fluid (SF) by fluorescence assay while anti-C. trachomatis IgA/IgM antibodies were estimated in SF/venous blood by ELISA. C. trachomatis MOMP was evident by the presence of elementary bodies in SF of 9 ReA PCR-positive patients (30%; p < 0.05 versus controls). Local secretory IgA antibodies were detected in 12 (40%) patients with ReA (p < 0.0001 versus controls); among 12 patients with anti-chlamydial IgA antibodies, 9 showed the presence of both MOMP and IgA antibodies in SF. 58.3% ReA patients (7/12) with secretory IgA antibodies were also positive for circulatory IgA antibodies (p < 0.01 versus controls). Serum IgM antibodies were present in 4 ReA (13.3%) and in 1 RA (3.3%) patient, respectively. In conclusion, the present study suggests that in ReA patients with chronic, persistent C. trachomatis infection in synovium, the chlamydial MOMP is triggering factor for generating a protective immune response by inducing anti-C. trachomatis IgA antibodies in the SF of large number of patients.
25678252 Blocking of LFA-1 enhances expansion of Th17 cells induced by human CD14(+) CD16(++) noncl 2015 May Among human peripheral blood (PB) monocyte (Mo) subsets, the classical CD14(++) CD16(-) (cMo) and intermediate CD14(++) CD16(+) (iMo) Mos are known to activate pathogenic Th17 responses, whereas the impact of nonclassical CD14(+) CD16(++) Mo (nMo) on T-cell activation has been largely neglected. The aim of this study was to obtain new mechanistic insights on the capacity of Mo subsets from healthy donors (HDs) to activate IL-17(+) T-cell responses in vitro, and assess whether this function was maintained or lost in states of chronic inflammation. When cocultured with autologous CD4(+) T cells in the absence of TLR-2/NOD2 agonists, PB nMos from HDs were more efficient stimulators of IL-17-producing T cells, as compared to cMo. These results could not be explained by differences in Mo lifespan and cytokine profiles. Notably, however, the blocking of LFA-1/ICAM-1 interaction resulted in a significant increase in the percentage of IL-17(+) T cells expanded in nMo/T-cell cocultures. As compared to HD, PB Mo subsets of patients with rheumatoid arthritis were hampered in their T-cell stimulatory capacity. Our new insights highlight the role of Mo subsets in modulating inflammatory T-cell responses and suggest that nMo could become a critical therapeutic target against IL-17-mediated inflammatory diseases.
27381006 VIP impairs acquisition of the macrophage proinflammatory polarization profile. 2016 Dec This study tested the hypothesis that vasoactive intestinal peptide (VIP) is able to modify the macrophage inflammatory profile, thus supporting its therapeutic role in autoimmune diseases. Macrophages are innate immune cells that display a variety of functions and inflammatory profiles in response to the environment that critically controls their polarization. Deregulation between the pro- and anti-inflammatory phenotypes has been involved in different pathologies. Rheumatoid arthritis (RA) is an autoimmune disease, in which macrophages are considered central effectors of synovial inflammation, displaying a proinflammatory profile. VIP is a pleiotropic neuropeptide with proven anti-inflammatory actions. As modulation of the macrophage phenotype has been implicated in the resolution of inflammatory diseases, we evaluated whether VIP is able to modulate human macrophage polarization. In vitro-polarized macrophages by GM-CSF (GM-MØ), with a proinflammatory profile, expressed higher levels of VIP receptors, vasoactive intestinal polypeptide receptors 1 and 2 (VPAC1 and VPAC2, respectively), than macrophages polarized by M-CSF (M-MØ) with anti-inflammatory activities. RA synovial macrophages, according to their GM-CSF-like polarization state, expressed both VPAC1 and VPAC2. In vitro-generated GM-MØ exposed to VIP exhibited an up-regulation of M-MØ gene marker expression, whereas their proinflammatory cytokine profile was reduced in favor of an anti-inflammatory function. Likewise, in GM-MØ, generated in the presence of VIP, VIP somehow changes the macrophages physiology profile to a less-damaging phenotype. Therefore, these results add new value to VIP as an immunomodulatory agent on inflammatory diseases.
27820809 Regulation of autoantibody activity by the IL-23-T(H)17 axis determines the onset of autoi 2017 Jan The checkpoints and mechanisms that contribute to autoantibody-driven disease are as yet incompletely understood. Here we identified the axis of interleukin 23 (IL-23) and the T(H)17 subset of helper T cells as a decisive factor that controlled the intrinsic inflammatory activity of autoantibodies and triggered the clinical onset of autoimmune arthritis. By instructing B cells in an IL-22- and IL-21-dependent manner, T(H)17 cells regulated the expression of β-galactoside α2,6-sialyltransferase 1 in newly differentiating antibody-producing cells and determined the glycosylation profile and activity of immunoglobulin G (IgG) produced by the plasma cells that subsequently emerged. Asymptomatic humans with rheumatoid arthritis (RA)-specific autoantibodies showed identical changes in the activity and glycosylation of autoreactive IgG antibodies before shifting to the inflammatory phase of RA; thus, our results identify an IL-23-T(H)17 cell-dependent pathway that controls autoantibody activity and unmasks a preexisting breach in immunotolerance.
26036592 Pneumococcal polysaccharide vaccination in rheumatoid arthritis patients receiving tacroli 2015 Jun 3 INTRODUCTION: In rheumatoid arthritis (RA) patients receiving immunosuppressive treatments, vaccination against Streptococcus pneumoniae is recommended. The objective of the study was to evaluate the effects of tacrolimus (TAC) on immune response following administration of a 23-valent pneumococcal polysaccharide vaccine (PPSV23) in patients with established RA. METHODS: Patients with RA (n = 133) were vaccinated with PPSV23. Patients were classified into TAC (n = 29), methotrexate (MTX) (n = 55), control (n = 35), and TAC/MTX (n = 14) treatment groups. We measured the concentrations of pneumococcal serotypes 6B and 23F by using an enzyme-linked immunosorbent assay and determined antibody functionality by using a multiplexed opsonophagocytic killing assay, reported as the opsonization index (OI), before and 4 to 6 weeks after vaccination. A positive antibody response was defined as at least a twofold increase in the IgG concentration or as at least a 10-fold increase in the OI. RESULTS: IgG concentrations and OIs were significantly increased in all treatment groups after PPSV23 vaccination. The TAC treatment group appears to respond in a manner similar to that of the RA control group in terms of 6B and 23F serotype concentration and function. In contrast, the MTX group had the lowest immune response. Patients who received a combination of TAC and MTX (TAC/MTX) also had a diminished immune response compared with those who received TAC alone. CONCLUSIONS: TAC monotherapy does not appear to impair PPSV23 immunogenicity in patients with RA, whereas antibody production and function may be reduced when TAC is used with MTX. Thus, PPSV23 administration during ongoing TAC treatment should be encouraged for infection-prone TAC-treated patients with rheumatic diseases. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry: UMIN000009566. Registered 12 December 2012.
24285492 Free fatty acids: potential proinflammatory mediators in rheumatic diseases. 2015 Jan OBJECTIVES: Due to their role in inflammatory metabolic diseases, we hypothesised that free fatty acids (FFA) are also involved in inflammatory joint diseases. To test this hypothesis, we analysed the effect of FFA on synovial fibroblasts (SF), human chondrocytes and endothelial cells. We also investigated whether the toll-like receptor 4 (TLR4), which can contribute to driving arthritis, is involved in FFA signalling. METHODS: Rheumatoid arthritis SF, osteoarthritis SF, psoriatic arthritis SF, human chondrocytes and endothelial cells were stimulated in vitro with different FFA. Immunoassays were used to quantify FFA-induced protein secretion. TLR4 signalling was inhibited extracellularly and intracellularly. Fatty acid translocase (CD36), responsible for transporting long-chain FFA into the cell, was also inhibited. RESULTS: In rheumatoid arthritis synovial fibroblasts (RASF), FFA dose-dependently enhanced the secretion of the proinflammatory cytokine IL-6, the chemokines IL-8 and MCP-1, as well as the matrix-degrading enzymes pro-MMP1 and MMP3. The intensity of the response was mainly dependent on the patient rather than on the type of disease. Both saturated and unsaturated FFA showed similar effects on RASF, while responses to the different FFA varied for human chondrocytes and endothelial cells. Extracellular and intracellular TLR4 inhibition as well as fatty acid transport inhibition blocked the palmitic acid-induced IL-6 secretion of RASF. CONCLUSIONS: The data show that FFA are not only metabolic substrates but may also directly contribute to articular inflammation and degradation in inflammatory joint diseases. Moreover, the data suggest that, in RASF, FFA exert their effects via TLR4 and require extracellular and intracellular access to the TLR4 receptor complex.
27930519 Who are the users of a traditional Chinese sanfu acupoint herbal patching therapy in China 2016 Dec Sanfu acupoint herbal patching (SAHP) is a unique traditional Chinese medicine therapy, which has become popular for preventing acute attack of respiratory diseases such as asthma and chronic obstructive pulmonary disease, in many regions of mainland China. However, the knowledge about its users is lacking, especially the characteristics of the users and their experience and perspectives.To investigate the demographics of users, conditions for its use and the previous experience of SAHP, as well as users' perspectives to provide baseline information for its practice.A cross-sectional consecutive-sample survey was conducted at outpatient departments from 3 traditional Chinese medicine hospitals in northern China. Each participant completed a questionnaire, after informed consent. Data description and analyses were done using SPSS 20.0.Among 949 SAHP users from 3 hospitals, female was predominant (n = 592; 62.4%), aged from 2 to 96 years (median = 52 years). 64.7% (380/587) of regular users have applied consecutively for 3 years or over, and the self-perceived satisfaction rates of respiratory diseases were from 45.9% to 77.7%. Positive attitude toward traditional Chinese medicine was the top reason for choosing SAHP. 42.4% of users held a motivation of being cured by SAHP and with great outcome expectancy on SAHP (70.8%).SAHP users were mainly female adults or elderly population; more than half were regular users, who predominantly used SAHP for various chronic respiratory diseases during their stable stage. The majority of users expressed satisfaction to previous SAHP for their respiratory diseases. 42.4% of users held a motivation of being cured by SAHP and with great outcome expectancy on SAHP (70.8%). The findings from this survey deserve further clinical trials for their clinical effectiveness.
25573840 Cost-effectiveness of TNF inhibitors vs synthetic disease-modifying antirheumatic drugs in 2015 Jul OBJECTIVE: The objective of this study was to estimate the additional costs and health benefits of adding a TNF inhibitor (TNFi) (adalimumab, certolizumab, etanercept, golimumab, infliximab) to a synthetic DMARD (sDMARD), e.g. MTX, in patients with RA. METHODS: We developed the Norwegian RA model as a Markov model simulating 10 years of treatment with either TNFi plus sDMARDs (TNFi strategy) or sDMARDs alone (synthetic strategy). Patients in both strategies started in one of seven health states, based on the Short Form-6 Dimensions (SF-6D). The patients could move to better or worse health states according to transition probabilities. In the TNFi strategy, patients could stay on TNFi (including switch of TNFi), or switch to non-TNFi-biologics (abatacept, rituximab, tocilizumab), sDMARDs or no DMARD. In the synthetic strategy, patients remained on sDMARDs. Data from two observational studies were used for the assessment of resource use and utilities in the health states. Health benefits were evaluated using the EuroQol-5 Dimensions (EQ-5D) and SF-6D. RESULTS: The Norwegian RA model predicted that 10-year discounted health care costs totalled €124,942 (€475,266 including production losses) for the TNFi strategy and €65,584 (€436,517) for the synthetic strategy. The cost per additionally gained quality-adjusted life-year of adding a TNFi was €92,557 (€60,227 including production losses) using SF-6D and €61,285 (€39,841) using EQ-5D. Including health care costs only, the probability that TNFi treatment was cost-effective was 90% when using EQ-5D, assuming a Norwegian willingness-to-pay level of €67,300. CONCLUSION: TNFi treatment for RA is cost-effective when accounting for production losses. Excluding production losses, TNFi treatment is cost-effective using EQ-5D, but not SF-6D.
26739679 Anti-inflammatory and anti-oxidative effects of herbal preparation EM 1201 in adjuvant art 2015 BACKGROUND AND OBJECTIVE: The purpose of the present study was to examine the anti-arthritic and antioxidant effects of herbal and active organic ingredient complex (EM 1201) in rats with experimental adjuvant arthritis (AA). MATERIALS AND METHODS: AA was induced in 30 male Wistar rats by intradermal injection of complete Freund's adjuvant into the left hind paw. The course of disease in 30 rats in response to the treatment with EM 1201 and diclofenac, the parameters including body weight, joint swelling, blood indices pro-/antioxidant status of blood serum, and histology of joints and the liver, were investigated. RESULTS: Preparation EM 1201 showed anti-inflammatory effect analogous to diclofenac, improved blood indices, significantly decreased joint swelling and histological changes in them. Joint swelling was suppressed by 29%-42.8% and 9.3%-34.4% in response to administration of EM 1201 and diclofenac during the entire experiment. Both preparations significantly suppressed pannus formation, general inflammatory reaction and edema in soft periarticular tissues and synovium, diminished MDA level and elevated AOA in the blood serum. Significantly lower absolute and relative weight of the liver and lower dystrophic processes in it, and general inflammatory infiltration of hepatic stroma proved the positive effect of treatment with EM 1201. CONCLUSIONS: The present study suggests that EM 1201 has protective activity against arthritis and demonstrated its potential beneficiary effect analogical to diclofenac. Anti-inflammatory and anti-oxidative effect of EM 1201 in rats with AA support the need of further investigations by using it as supplementary agent alone or together with other anti-arthritic drugs in the treatment of rheumatoid arthritis.
26117428 Novel insight into drug repositioning: Methylthiouracil as a case in point. 2015 Sep Drug repositioning refers to the development of existing drugs for new indications. These drugs may have (I) failed to show efficacy in late stage clinical trials without safety issues; (II) stalled in the development for commercial reasons; (III) passed the point of patent expiry; or (IV) are being explored in new geographic markets. Over the past decade, pressure on the pharmaceutical industry caused by the 'innovation gap' owing to rising development costs and stagnant product output have become major reasons for the growing interest in drug repositioning. Companies that offer a variety of broad platforms for identifying new indications have emerged; some have been successful in building their own pipelines of candidates with reduced risks and timelines associated with further clinical development. The business models and platforms offered by these companies will be validated if they are able to generate positive proof-of-concept clinical data for their repositioned compounds. This review describes the strategy of biomarker-guided repositioning of chemotherapeutic drugs for inflammation therapy, considering the repositioning of methylthiouracil (MTU), an antithyroid drug, as a potential anti-inflammatory reagent.
26812164 Atherosclerosis in Sjögren's syndrome: evidence, possible mechanisms and knowledge gaps. 2016 Jan Inflammation has been associated with higher cardiovascular risk in rheumatic autoimmune diseases like rheumatoid arthritis (RA) and systemic lupus erythematosus. More recently, primary Sjögren's syndrome (pSS) was also demonstrated as an independent risk factor for cardiovascular disease, emerging as a new interesting model to study atherosclerosis in autoimmune diseases. Patients with pSS have a higher prevalence of developing traditional cardiovascular risk factors like hypertension and dyslipidaemia predisposing for endothelial dysfunction and premature atherosclerosis. However, the disease-specific mechanisms for premature atherosclerosis in pSS are not fully understood. The aim of this review was to critically analyse the current literature on cardiovascular risks in pSS and to discuss the traditional and disease-associated risk factors. We also suggest possible new mechanisms that should be explored in future research to close the current knowledge gaps on the association of pSS, premature atherosclerosis, and clinical cardiovascular disease.
26209895 Eosinophilia in Rheumatologic/Vascular Disorders. 2015 Aug Peripheral and tissue eosinophilia can be a prominent feature of several unique rheumatologic and vascular diseases. These diseases span a wide range of clinical features, histologic findings, therapeutic approaches, and outcomes. Despite the rare nature of these entities--which makes large-scale studies challenging--knowledge has continued to grow regarding their epidemiology, pathophysiology, and management. This review compares and contrasts 5 rheumatologic and vascular conditions in which eosinophilia can be seen: eosinophilic granulomatosis with polyangiitis (Churg-Strauss), immunoglobulin G4-related disease, diffuse fasciitis with eosinophilia, eosinophilia-myalgia syndrome, and eosinophilic myositis.
25788188 Long-term use of methotrexate does not result in hepatitis B reactivation in rheumatologic 2015 Apr BACKGROUND AND OBJECTIVE: Hepatitis B virus (HBV) infection is still prevalent in Asia, including Thailand. HBV can archive in hepatocytes for life and can reactivate after immunosuppression and chemotherapy administration. Use of immunosuppressive agents is recommended in many rheumatologic diseases and reactivation of HBV can occur. Data regarding the effect of methotrexate (MTX) on HBV reactivation is scanty. MTX is a well known cause of hepatic fibrosis but its effect on HBV reactivation is not clearly understood. There is no specific recommendation for HBV prophylaxis for patients using MTX. This study aimed to determine the prevalence of HBV seromarkers in rheumatologic patients who were treated with long-term MTX and to evaluate the hepatitis outcome in the patients with positive HBV markers. METHODS: This was a cross-sectional study at the Rheumatology Clinic, Siriraj Hospital, Bangkok, Thailand. Patients aged 15 years or older treated with MTX more than 24 weeks were invited in the study. Review of medical history, MTX prescription and dosage during the last 52 weeks, blood tests for liver function tests, HBV serology, and HBV DNA viral load were performed. The exclusion criteria included patients who were treated with biological DMARDs, drugs active against HBV, known co-infection with HCV or HIV and previous diagnosis of cirrhosis from any causes or presence of hepatocellular carcinoma. RESULTS: A total of 173 patients were enrolled (153 females, 20 males, mean age of 52.6 ± 13.6 years). The majority of patients were diagnosed with rheumatoid arthritis (67.0%), SLE (13.9%), spondyloarthopathies (8.7%) and others (10.4%). Thirty percent of them (55/173) had no previous data for HBV seromarkers. Among 118 patients who had baseline data, only one patient (0.8%) had HBsAg positive. Average duration of treatment was 9.9 years and MTX dose prescribed was 571.6 ± 240.4 mg during the last 52 weeks. Out of 173 patients, only two had clinically significant hepatitis (1.16%) and one was HBsAg positive (0.58%). Ninety-six patients (55.5%) were negative for all HBV seromarkers, 67/173 (38.7%) positive for anti-HBs antibody and 65/173 (37.6%) positive for anti-HBc IgG. Only one in 65 patients (1.5%) who had any positive HBV seromarkers had HBV DNA detectable. CONCLUSION: Prevalence of HBsAg positive rheumatologic patients treated with MTX in Thailand was only 0.58%, which was lower than the general Thai population. About one-third of the patients had exposure to HBV as demonstrated by presence of anti-HBc IgG (37.6%), but none of them had hepatitis B reactivation during 9.9 years of MTX treatment. Moreover, one case with HBsAg positive had been receiving MTX without HBV prophylaxis for 5 years but had no evidence of HBV flare and evidence of fibrosis. From our study, long-term MTX in patients exposed to HBV was safe and not associated with hepatitis flare. However, more study is needed as to whether HBV prophylaxis is required.
27486778 Contribution of a Non-classical HLA Gene, HLA-DOA, to the Risk of Rheumatoid Arthritis. 2016 Aug 4 Despite the progress in human leukocyte antigen (HLA) causal variant mapping, independent localization of major histocompatibility complex (MHC) risk from classical HLA genes is challenging. Here, we conducted a large-scale MHC fine-mapping analysis of rheumatoid arthritis (RA) in a Japanese population (6,244 RA cases and 23,731 controls) population by using HLA imputation, followed by a multi-ethnic validation study including east Asian and European populations (n = 7,097 and 23,149, respectively). Our study identified an independent risk of a synonymous mutation at HLA-DOA, a non-classical HLA gene, on anti-citrullinated protein autoantibody (ACPA)-positive RA risk (p = 1.4 × 10(-9)), which demonstrated a cis-expression quantitative trait loci (cis-eQTL) effect on HLA-DOA expression. Trans-ethnic comparison revealed different linkage disequilibrium (LD) patterns in HLA-DOA and HLA-DRB1, explaining the observed HLA-DOA variant risk heterogeneity among ethnicities, which was most evident in the Japanese population. Although previous HLA fine-mapping studies have identified amino acid polymorphisms of the classical HLA genes as driving genetic susceptibility to disease, our study additionally identifies the dosage contribution of a non-classical HLA gene to disease etiology. Our study contributes to the understanding of HLA immunology in human diseases and suggests the value of incorporating additional ancestry in MHC fine-mapping.
25937569 Genetic Basis of Common Human Disease: Insight into the Role of Missense SNPs from Genome- 2015 Jul 3 Recent genome-wide association studies (GWAS) have led to the reliable identification of single nucleotide polymorphisms (SNPs) at a number of loci associated with increased risk of specific common human diseases. Each such locus implicates multiple possible candidate SNPs for involvement in disease mechanism. A variety of mechanisms may link the presence of an SNP to altered in vivo gene product function and hence contribute to disease risk. Here, we report an analysis of the role of one of these mechanisms, missense SNPs (msSNPs) in proteins in seven complex trait diseases. Linkage disequilibrium information was used to identify possible candidate msSNPs associated with increased disease risk at each of 356 loci for the seven diseases. Two computational methods were used to estimate which of these SNPs has a significant impact on in vivo protein function. 69% of the loci have at least one candidate msSNP and 33% have at least one predicted high-impact msSNP. In some cases, these SNPs are in well-established disease-related proteins, such as MST1 (macrophage stimulating 1) for Crohn's disease. In others, they are in proteins identified by GWAS as likely candidates for disease relevance, but previously without known mechanism, such as ADAMTS13 (ADAM metallopeptidase with thrombospondin type 1 motif, 13) for coronary artery disease. In still other cases, the missense SNPs are in proteins not previously suggested as disease candidates, such as TUBB1 (tubulin, beta 1, class VI) for hypertension. Together, these data support a substantial role for this class of SNPs in susceptibility to common human disease.
25865263 Detection of circulating immune complexes of human IgA and beta 2 glycoprotein I in patien 2015 Jul BACKGROUND: Patients with antiphospholipid syndrome (APS) have a hypercoagulable condition associated with the presence of antiphospholipid autoantibodies (aPL). Consensus antibodies for diagnosis are lupus anticoagulant, anti-beta2 glycoprotein I (B2GPI) and anticardiolipin (IgG or IgM). Circulating immunocomplexes (CIC) of B2GPI associated with IgM or IgG were reported. Isolated IgA aB2GPI antibodies have achieved high diagnostic value although specific CIC of B2GPI bounded to IgA (B2A-CIC) has still not been described. CIC detection assays are mainly based on interaction with complement and are not appropriate to detect B2A-CIC because IgA does not fix complement using the classical pathway. PATIENTS AND METHODS: Sera from healthy blood donors (N= 247) and from patients with thrombosis background and isolate positive for IgA aB2GPI (N = 68) were studied in a case-control study. Two methods were applied, these being a capture ELISA to quantify specific B2A-CIC and quantification of total IgA anti-B2GPI after dissociating CIC. RESULTS: B2A-CIC values in APS-patients were 19.27 ± 2.6 AU vs 6.1 ± 0.4 AU in blood donors (p < 0.001). There were 36.4% B2A-CIC positive patients (cutoff 21 AU) versus 5.5% in blood donors (p < 0.001). Dissociated IgA aB2GPI levels (total IgA aB2GPI) were 146.8 ± 10.8 IU/mL in patients vs. 22.4 IU/mL in controls (p < 0.001). B2A-CIC was independent of B2GPI and autoantibodies IgA aB2GPI serum levels. CONCLUSION: B2A-CIC can be identified and quantified in an easy and reproducible manner using two complement-independent methods. The use of these tests in prospective studies will allow better understanding of the prognosis and outcome of patients.
25269884 Determination of Anticyclic Citrullinated Peptide Based on Biotin-Streptavidin-Amplified T 2015 Nov BACKGROUND: A rapid and sensitive time-resolved fluoroimmunoassay (TRFIA) based on the biotin-streptavidin amplification system was developed for the determination of anticyclic citrullinated peptide (anti-CCP). METHODS: Europium-labeled streptavidin derivatives combined with europium and anhydride of diethylene triamine pentaacetic acid were used to label streptavidin, biotin was coupled with rabbit anti-human IgG to form a biotin-anti-human IgG bridge between streptavidin-europium and the anti-CCP antibody in the immunoassay. The anti-CCP assay was carried out by measuring the fluorescence of Eu(3+) -streptavidin at 615 nm. RESULTS: The presented method produced a wide linear range from 0.58 to 9,463 U/ml, while it was only 591.4-18.48 U/ml when using an ELISA kit, and featured a detection limit up to 0.5 U/ml for anti-CCP. The values determined by the biotin-streptavidin-TRFIA and ELISA correlated well (R(2) = 0.8927). The method was applied to determine anti-CCP in serum samples with satisfied recoveries of 96.45-104.63%. CONCLUSION: The assay results obtained by the present method showed that biotin-streptavidin-amplified TRFIA improve the traditional ELISA kit for anti-CCP detection. Therefore, it offers a better alternative immunoassay in rheumatoid arthritis management.
25444344 Subjective and objective screening tests for hydroxychloroquine toxicity. 2015 Feb OBJECTIVE: To compare subjective and objective clinical tests used in the screening for hydroxychloroquine retinal toxicity to multifocal electroretinography (mfERG) reference testing. DESIGN: Prospective, single-center, case control study. PARTICIPANTS: Fifty-seven patients with a previous or current history of hydroxychloroquine treatment of more than 5 years' duration. METHODS: Participants were evaluated with a detailed medical history, dilated ophthalmologic examination, color fundus photography, fundus autofluorescence (FAF) imaging, spectral-domain (SD) optical coherence tomography (OCT), automated visual field testing (10-2 visual field mean deviation [VFMD]), and mfERG testing. We used mfERG test parameters as a gold standard to divide participants into 2 groups: those affected by hydroxychloroquine-induced retinal toxicity and those unaffected. MAIN OUTCOME MEASURES: We assessed the association of various imaging and psychophysical variables in the affected versus the unaffected group. RESULTS: Fifty-seven study participants (91.2% female; mean age, 55.7±10.4 years; mean duration of hydroxychloroquine treatment, 15.0±7.5 years) were divided into affected (n = 19) and unaffected (n = 38) groups based on mfERG criteria. Mean age and duration of hydroxychloroquine treatment did not differ statistically between groups. Mean OCT retinal thickness measurements in all 9 macular subfields were significantly lower (<40 μm) in the affected group (P < 0.01 for all comparisons) compared with those in the unaffected group. Mean VFMD was 11 dB lower in the affected group (P < 0.0001). Clinical features indicative of retinal toxicity were scored for the 2 groups and were detected in 68.4% versus 0.0% using color fundus photographs, 73.3% versus 9.1% using FAF images, and 84.2% versus 0.0% on the scoring for the perifoveal loss of the photoreceptor ellipsoid zone on SD-OCT for affected and unaffected participants, respectively. Using a polynomial modeling approach, OCT inner ring retinal thickness measurements and Humphrey 10-2 VFMD were identified as the variables associated most strongly with the presence of hydroxychloroquine as defined by mfERG testing. CONCLUSIONS: Optical coherence tomography retinal thickness and 10-2 VFMD are objective measures demonstrating clinically useful sensitivity and specificity for the detection of hydroxychloroquine toxicity as identified by mfERG, and thus may be suitable surrogate tests.
26007152 Polymorphism of VEGF gene in susceptibility to chronic immune-mediated inflammatory diseas 2015 Aug Background Vascular endothelial growth factor (VEGF) is an important angiogenic factor and may be connected with chronic immune-mediated inflammatory diseases (IMIDs) to some extent. However, previous researches about the relationship between the +405G>C (dbSNP: rs2010963) polymorphism in VEGF gene and the risk of IMIDs are controversial and inconsistent. So we conducted this meta-analysis to assess whether the relationship between the +405G>C polymorphism in the 5'-UTR region of VEGF gene and IMID susceptibility exists. Methods Our literature search was conducted on the PubMed, Embase, Web of science, Chinese National Knowledge Infrastructure, and Chinese Biomedical databases to retrieve for eligible studies. Odds ratios as well as their 95 % confidence intervals were utilized to deduce the possible relationship. Results A total number of 5175 patients with IMIDs and 7069 healthy controls from 27 case-control studies were included. For the overall eligible data collected in our meta-analysis, there was no marked relationship between +405G>C polymorphism and the risk of IMIDs. However, subgroup analysis by ethnicity suggested that +405C allele could be a protective factor for IMIDs in Asians, whereas an opposite conclusion was drawn in Caucasians. Conclusion Thus, we may come to the conclusion that the VEGF +405G>C polymorphism could be associated with IMIDs, and the correlation might vary with ethnic groups.