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ID PMID Title PublicationDate abstract
23887439 Drug levels, anti-drug antibodies, and clinical efficacy of the anti-TNFα biologics in rh 2013 Oct The objectives of this study are to evaluate the effect of anti-drug antibodies on the clinical efficacy and withdrawal rate of the anti-TNFα biologics in patients with rheumatic diseases. Consecutive patients with rheumatic diseases recently commenced on anti-TNFα biologics were recruited. Serum samples were collected for assay of drug level and antibody titer against the corresponding biologics. Comparison of the clinical efficacy and drug retention rate was performed between patients with and without anti-drug antibodies. Fifty-eight Chinese patients were studied (64 % women; age 47.8 ± 12.9 years; disease duration 6.7 ± 6.4 years). The proportion of patients using infliximab (IFX), adalimumab (ADA), and etanercept (ETN) was 41, 28, and 31 %, respectively. Antibodies against IFX, ADA, and ETN were demonstrated in 12(50 %), 5(31 %) and 0(0 %) patients, respectively. Patients who developed anti-drug antibodies had significantly lower levels of the corresponding drugs (IFX level: 0.004 ± 0.01 vs 3.81 ± 3.49 μg/ml; p = 0.002; ADA level: 0.0 vs 7.6 ± 8.3 μg/ml; p = 0.008). Anti-drug antibody-positive patients had a significantly higher cumulative drug withdrawal rate due to inefficacy (64.7 and 71.8 % vs 10.3 and 10.3 % at month 12 and month 24, respectively; p < 0.001). In rheumatoid arthritis and psoriatic arthritis, non-responders was significantly more frequent in antibody-positive patients (54 vs 13 %; p = 0.01). In spondyloarthritis, the improvement in ankylosing spondylitis disease activity score was significant in patients without antibodies (3.89 ± 0.82 to 2.22 ± 0.86; p = 0.01) but not in those with anti-drug antibodies (3.40 ± 1.67 to 3.23 ± 1.40; p = 0.73). We concluded that the presence of neutralizing antibodies is associated with lower serum levels of the anti-TNFα biologics, leading to lower efficacy and higher withdrawal rate.
24690143 "Design characteristics of the CORRONA CERTAIN study: a comparative effectiveness study of 2014 Apr 1 BACKGROUND: Comparative effectiveness research has recently attracted considerable attention. The Comparative Effectiveness Registry to study Therapies for Arthritis and Inflammatory Conditions (CERTAIN) is an ongoing prospective cohort study of adult patients with Rheumatoid Arthritis (RA). METHODS/DESIGN: CERTAIN uses the existing Consortium of Rheumatology Researchers of North America (CORRONA) network of participating private and academic sites in order to recruit patients fulfilling the 1987 ACR criteria that have at least moderate disease activity. Patients starting or switching biologic agents either anti-TNF therapy or a non anti-TNF biologic are eligible for enrollment, depending on the treatment selected by their physician. Enrollment is expected to be completed by March of 2014, and 2711 patients will participate in the study. As of October 7th 2013, 2234 patients have been enrolled. Patient visits and laboratory blood work are mandated every three months for one year. Safety data is collected through one year and beyond. The primary comparative effectiveness endpoint is attainment of low RA disease activity at one year among patients who have been exposed to at least one prior TNF-α inhibitor agent prior to enrollment. Multiple secondary effectiveness and safety endpoints will be addressed by investigating the entire population enrolled (naïve and biologic experienced). DISCUSSION: The unique design features of CERTAIN will inform comparative effectiveness and safety questions for choosing biologic agents for the management of RA.
24403823 Rituximab for the treatment of rheumatoid arthritis: an update. 2013 Dec 27 Rituximab is a chimeric monoclonal antibody that targets the CD20 molecule expressed on the surface of B cells. It was first used in the treatment of non-Hodgkin's lymphoma and later approved for the treatment of rheumatoid arthritis (RA) that does not respond adequately to disease-modifying antirheumatic drugs, including the anti-tumor-necrosis-factor (TNF) biologics. Sustained efficacy in RA can be achieved by repeated courses of rituximab. However, the optimal dose and retreatment schedule of rituximab in RA remains to be established. Seropositivity, complete B cell depletion shortly after treatment, and previous failure to no more than one anti-TNF agent are three factors associated with greater clinical benefits to rituximab. Infusion reaction to the first dose of rituximab occurs in approximately 25% of RA patients, and the incidence reduces with subsequent exposure. Immunogenicity to the chimeric compound occurs in 11% of RA patients, but this does not correlate with its efficacy in B cell depletion. Extended observation of randomized controlled trials in RA does not reveal a significant increase in the incidence of serious infections related to rituximab compared to placebo groups, and the infection rate remains static over time. Repeated treatment with rituximab is associated with hypogammaglobulinemia, which may increase the risk of serious, but rarely opportunistic, infections. Reactivation of occult hepatitis B infection has been reported in RA patients receiving rituximab, but no increase in the incidence of tuberculosis was observed. Screening for baseline serum immunoglobulin G level and hepatitis B status (including occult infection) is important, especially in Asian countries where hepatitis B infection is prevalent. The rare but fatal progressive multifocal leukoencephalopathy linked to the use of rituximab has to be noted. Postmarketing surveillance and registry data, particularly in Asia, are necessary to establish the long-term efficacy and safety of rituximab in the treatment of RA.
25226167 Risk of developing depressive disorders following rheumatoid arthritis: a nationwide popul 2014 BACKGROUND & AIMS: To evaluate the risk of depressive disorders among rheumatoid arthritis (RA) by using the Taiwan National Health Insurance Research Database (NHIRD). METHODS: We conducted a retrospective study of a matched cohort of 18 285 participants (3 657 RA patients and 14 628 control patients) who were selected from the NHIRD. Patients were observed for a maximum of 10 years to determine the rates of newly diagnosed depressive disorders, and Cox regression was used to identify the risk factors associated with depressive disorders in RA patients. RESULTS: During the 10-year follow-up period, 205 (11.2 per 1000 person-years) RA patients and 384 (5.1 per 1000 person-years) control patients were diagnosed with depressive disorders. In RA patients, most depressive disorders (n = 163, 80%) developed with five years of being diagnosed with RA. The incidence risk ratio of depressive disorders between RA patients and control patients was 2.20 (95% confidence interval [CI], 1.84-2.61, P<.001). After adjusting for age, sex, and comorbidities, RA patients were 2.06 times more likely to develop depressive disorders (95% CI, 1.73-2.44, P<.001) compared with the control patients. Hyperthyroidism (HR = 1.67) was an independent risk factor for depressive disorders in patients with RA. CONCLUSIONS: The likelihood of developing depressive disorders is greater among RA patients than among patients without RA. Symptoms of depression should be sought in patients with RA.
22556118 Physicians' explanations for apparent gaps in the quality of rheumatology care: results fr 2013 Feb OBJECTIVE: The metrics used to assess quality of care and pay for performance in rheumatology are increasingly important. The Centers for Medicare and Medicaid Services established the Physician Quality Reporting System (PQRS) to allow physicians to report performance measures for many conditions, including osteoporosis and rheumatoid arthritis (RA). We described the frequency and nature of physician-reported reasons why recommended care for individual osteoporosis and RA patients was not provided. METHODS: Using national data on Medicare fee-for-service beneficiaries (2007-2009), we identified health care providers reporting on quality of care for any of 3 osteoporosis or 3 RA measures. PQRS reason codes allowed physicians to submit explanations why recommended care was not given. RESULTS: In 2009, 1,775 physicians reported on ≥1 osteoporosis PQRS measure and 630 physicians reported on ≥1 RA measure. For the older women whose physician reported on lifetime dual x-ray absorptiometry screening at least once since the age of 60 years via PQRS, 76% received such screening. Among the patients with physician-diagnosed osteoporosis reported via PQRS, 82% received prescription osteoporosis medication in the preceding year. For RA medication use reported via PQRS, 89% of patients received a disease-modifying antirheumatic drug or a biologic agent. For the remaining 11-24% of osteoporosis and RA patients, physicians reported medical, patient, system, or other reasons why care was considered but not provided. CONCLUSION: A substantial fraction of Medicare enrollees who did not receive recommended osteoporosis or RA care had physician-documented reasons for why care was not provided. For Medicare and other health plans that implement penalties for apparent nonperformance or delivery of suboptimal care, it will be important to allow physicians to provide reasons that care was considered medically inappropriate, refused, or otherwise not feasible.
24286358 Intra-articular CD1c-expressing myeloid dendritic cells from rheumatoid arthritis patients 2013 Oct 20 INTRODUCTION: Myeloid dendritic cells (mDCs) are potent T cell-activating antigen-presenting cells that have been suggested to play a crucial role in the regulation of immune responses in many disease states, including rheumatoid arthritis (RA). Despite this, studies that have reported on the capacity of naturally occurring circulating mDCs to regulate T cell activation in RA are still lacking. This study aimed to evaluate the phenotypic and functional properties of naturally occurring CD1c (BDCA-1)+ mDCs from synovial fluid (SF) compared to those from peripheral blood (PB) of RA patients. METHODS: CD1c+ mDC numbers and expression of costimulatory molecules were assessed by fluorescence-activated cell sorting (FACS) analysis in SF and PB from RA patients. Ex vivo secretion of 45 inflammatory mediators by mDCs from SF and PB of RA patients was determined by multiplex immunoassay. The capacity of mDCs from SF to activate autologous CD4+ T cells was measured. RESULTS: CD1c+ mDC numbers were significantly increased in SF versus PB of RA patients (mean 4.7% vs. 0.6%). mDCs from SF showed increased expression of antigen-presenting (human leukocyte antigen (HLA) class II, CD1c) and costimulatory molecules (CD80, CD86 and CD40). Numerous cytokines were equally abundantly produced by mDCs from both PB and SF (including IL-12, IL-23, IL-13, IL-21). SF mDCs secreted higher levels of interferon γ-inducible protein-10 (IP-10), monokine induced by interferon γ (MIG) and, thymus and activation-regulated chemokine (TARC), but lower macrophage-derived chemokine (MDC) levels compared to mDCs from PB. mDCs from SF displayed a strongly increased capacity to induce proliferation of CD4+ T cells associated with a strongly augmented IFNγ, IL-17, and IL-4 production. CONCLUSIONS: This study suggests that increased numbers of CD1c+ mDCs in SF are involved in the inflammatory cascade intra-articularly by the secretion of specific T cell-attracting chemokines and the activation of self-reactive T cells.
25196430 The role of prostaglandin E2 receptor signaling of dendritic cells in rheumatoid arthritis 2014 Nov Prostaglandin E2 (PGE2), a very potent lipid mediator produced from arachidonic acid (AA) through the action of cyclooxygenase (COX) enzymes, is implicated in the regulation of dendritic cell (DC) functions such as differentiation ability, cytokine-producing capacity, Th-cell polarizing ability, migration and maturation. DCs are the most potent antigen-presenting cells and play major roles in both the induction of primary immune responses and tolerance. It is well established that PGE2 functions significantly in the pathogenesis of rheumatoid arthritis (RA). Although the role of PGE2 in RA has been studied extensively, the effects of PGE2 on DC biology and the role of DCs in RA have not become the focus of investigation until recently. Here, we summarize the latest progress in PGE2 research with respect to DC functions, as well as the role of PGE2 receptor signaling of DCs in the pathogenesis of RA.
24754504 Do women with premenopausal-onset rheumatoid arthritis have relative insufficiency or imba 2014 May Adrenocortical steroids may influence susceptibility to rheumatoid arthritis (RA). Serum levels of adrenocortical steroids in female RA patients not previously treated with glucocorticoids were reviewed in this paper, as were controlled cohort studies of predisease (pre-RA) and control (CN) women. Serum dehydroepiandrosterone sulfate (DHEAS) levels were lower in most reports of premenopausal-onset RA patients not treated with glucocorticoids and in the baseline levels in one cohort study of pre-RA females compared with CN subjects. The pre-RA versus CN cohort difference was confirmed in an independent laboratory. Basal DHEAS and cortisol levels correlated oppositely in pre-RA versus CN women, suggesting relative adrenocortical androgenic insufficiency in case subjects. Clinical observations of lower androstenedione levels in premenopausal RA patients were also reported in pre-RA versus CN subjects who had lower DHEAS and cortisol values. In summary, a minority of premenopausal-onset RA females had decreased adrenocortical androgenic steroid levels and exhibited an adrenal androgen-to-cortisol steroid imbalance.
23588946 Safety of abatacept administered intravenously in treatment of rheumatoid arthritis: integ 2013 Jun OBJECTIVE: To assess the overall safety, including rare events, of intravenous (IV) abatacept treatment in rheumatoid arthritis (RA). METHODS: Data from 8 clinical trials of IV abatacept in RA were pooled. Safety events were assessed during the short-term (duration ≤ 12 months) and cumulative (short-term plus longterm extensions) abatacept treatment periods. Incidence rates per 100 patient-years were calculated. Standardized incidence ratios (SIR) for hospitalized infections and malignancies were compared with external RA cohorts and, for malignancies, with the US general population. RESULTS: There were 3173 IV abatacept-treated patients with 2331 patient-years of exposure in the short-term periods, and 4149 IV abatacept-treated patients with 12,132 patient-years of exposure in the cumulative period. Incidence rates for serious infections were low and consistent over time (3.68 for abatacept vs 2.60 for placebo during the short-term, and 2.87 for abatacept during the cumulative period). Hospitalized infections were generally similar to external RA patient cohorts and were consistent over time. Incidence rates of malignancies were similar for abatacept- and placebo-treated patients during the short-term period (0.73 vs 0.59) and remained low during the abatacept cumulative period (0.73). SIR of some tissue-specific malignancies (e.g., colorectal and breast) in the cumulative period tended to be lower, while others (lymphoma and lung) tended to be higher, compared with the general population; however, incidence rates were comparable with RA cohorts. Autoimmune events were rare and infusion reactions uncommon. CONCLUSION: Longterm safety of IV abatacept was consistent with the short-term, with no unexpected events and low incidence rates of serious infections, malignancies, and autoimmune events.
24098138 Integrated enrichment analysis of variants and pathways in genome-wide association studies 2013 Pathway analyses of genome-wide association studies aggregate information over sets of related genes, such as genes in common pathways, to identify gene sets that are enriched for variants associated with disease. We develop a model-based approach to pathway analysis, and apply this approach to data from the Wellcome Trust Case Control Consortium (WTCCC) studies. Our method offers several benefits over existing approaches. First, our method not only interrogates pathways for enrichment of disease associations, but also estimates the level of enrichment, which yields a coherent way to promote variants in enriched pathways, enhancing discovery of genes underlying disease. Second, our approach allows for multiple enriched pathways, a feature that leads to novel findings in two diseases where the major histocompatibility complex (MHC) is a major determinant of disease susceptibility. Third, by modeling disease as the combined effect of multiple markers, our method automatically accounts for linkage disequilibrium among variants. Interrogation of pathways from eight pathway databases yields strong support for enriched pathways, indicating links between Crohn's disease (CD) and cytokine-driven networks that modulate immune responses; between rheumatoid arthritis (RA) and "Measles" pathway genes involved in immune responses triggered by measles infection; and between type 1 diabetes (T1D) and IL2-mediated signaling genes. Prioritizing variants in these enriched pathways yields many additional putative disease associations compared to analyses without enrichment. For CD and RA, 7 of 8 additional non-MHC associations are corroborated by other studies, providing validation for our approach. For T1D, prioritization of IL-2 signaling genes yields strong evidence for 7 additional non-MHC candidate disease loci, as well as suggestive evidence for several more. Of the 7 strongest associations, 4 are validated by other studies, and 3 (near IL-2 signaling genes RAF1, MAPK14, and FYN) constitute novel putative T1D loci for further study.
23695309 Membrane-type matrix metalloproteinases: key mediators of leukocyte function. 2013 Aug Leukocytes are major cellular effectors of the immune response. To accomplish this task, these cells display a vast arsenal of proteinases, among which, members of the MMP family are especially important. Leukocytes express several members of the MMP family, including secreted- and membrane-anchored MT- MMPs, which synergistically orchestrate an appropriate proteolytic reaction that ultimately modulates immunological responses. The MT-MMP subfamily comprises TM- and GPI-anchored proteinases, which are targeted to well-defined membrane microdomains and exhibit different substrate specificities. Whereas much information exists on the biological roles of secreted MMPs in leukocytes, the roles of MT-MMPs remain relatively obscure. This review summarizes the current knowledge on the expression of MT-MMPs in leukocyte and their contribution to the immune responses and to pathological conditions.
24673109 Balance between activating NKG2D, DNAM-1, NKp44 and NKp46 and inhibitory CD94/NKG2A recept 2014 Aug Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and synovial hyperplasia leading to progressive joint destruction. Fibroblast-like synoviocytes (FLS) are central components of the aggressive, tumour-like synovial structure termed pannus, which invades the joint space and cartilage. A distinct natural killer (NK) cell subset expressing the inhibitory CD94/NKG2A receptor is present in RA synovial fluid. Little is known about possible cellular interactions between RA-FLS and NK cells. We used cultured RA-FLS and the human NK cell line Nishi, of which the latter expresses an NK receptor repertoire similar to that of NK cells in RA synovial fluid, as an in vitro model system of RA-FLS/NK cell cross-talk. We show that RA-FLS express numerous ligands for both activating and inhibitory NK cell receptors, and stimulate degranulation of Nishi cells. We found that NKG2D, DNAM-1, NKp46 and NKp44 are the key activating receptors involved in Nishi cell degranulation towards RA-FLS. Moreover, blockade of the interaction between CD94/NKG2A and its ligand HLA-E expressed on RA-FLS further enhanced Nishi cell degranulation in co-culture with RA-FLS. Using cultured RA-FLS and the human NK cell line Nishi as an in vitro model system of RA-FLS/NK cell cross-talk, our results suggest that cell-mediated cytotoxicity of RA-FLS may be one mechanism by which NK cells influence local joint inflammation in RA.
22198693 Optic neuritis after infliximab therapy. 2013 Apr Demyelinating diseases were described in patients receiving anti-TNF agents. Optic neuritis (ON) induced by TNF blockers was already described in 22 cases in the literature. In this article, the authors report a 53-year-old woman with refractory rheumatoid arthritis that developed neuritis optica after the fourth dose of infliximab and had a good outcome after anti-TNF withdrawal, associated with glucocorticoid treatment. In addition, the previous cases of ON induced by anti-TNF agents were reviewed.
24602920 Reporting of patient-perceived impact of rheumatoid arthritis and axial spondyloarthritis 2014 Jul OBJECTIVE: RA and axial SpA have an important impact on patients' lives. The objective of this study was to explore the reporting of different aspects of that impact in publications, with a focus on differences between diseases and over time. METHODS: A systematic literature review retrieved all articles reporting on the life impact of RA or axial radiographic SpA in adults published within the last 10 years and issued from European research. The data were classified into physical impact (including pain, functional assessment and fatigue), psychological impact (including psychological distress and coping) and social impact (including relationships, family and social life). The number of articles published over time was analysed by linear regression. RESULTS: In all, 1352 abstracts were screened and 149 publications (40,056 patients) were analysed: 129 articles (86.5%) concerned RA and 16 (10.7%) concerned axial SpA. The mean number of articles reporting on the physical aspects of impact was 11.4 (s.d. 4.8) per 2-year period, but increased more than 2-fold (from 7 articles in 2001-3 to 15 in 2010-11), in particular due to recent publications on fatigue, whereas the number of articles on psychological aspects [mean 12.4 (s.d. 4.0)] decreased markedly after 2006. Publications reporting on social aspects [mean 8.2 (s.d. 4.1)] remained globally stable. CONCLUSION: In the era of biologics, there is an interest in the patient-perceived life impact of RA and axial SpA in the European literature, but the impact of RA has been the subject of greater exploration. There are clearly trends over time in the reporting of impact.
23763534 Anti-TNF treatments in rheumatoid arthritis: economic impact of dosage modification. 2013 Jun Rheumatoid arthritis (RA) is a chronic systemic disease that leads to increases in health system economic burden through direct and indirect costs, including chronic treatment, reduced productivity and premature mortality. Anti-TNF agents have represented a major advance in the treatment of RA. The most commonly used (adalimumab, etanercept and infliximab) have demonstrated their cost-effectiveness at label doses. However, physicians may need to adapt the treatment by increasing the dose when a drug is not effective enough or by reducing it when there is a sustained effectiveness. In a cross-sectional study conducted in our hospital in which information from RA patients treated with anti-TNF drugs under conventional and modified doses were collected, the authors analyzed the costs of the medication in order to estimate the mean patient-year cost, the annual costs related to clinical efficacy and the cost per responder patient to anti-TNF treatment when dosage modification is undertaken in daily clinical practice.
22258456 Interferon-gamma induced nitric oxide-mediated apoptosis of anemia of chronic disease in r 2013 Jan Proinflammatory cytokines play a role in the pathogenesis of anemia of chronic disease (ACD), which is a common cause of anemia in rheumatoid arthritis (RA). Anemia in RA is associated with increased apoptosis of erythroid cells. However, there is unclear information on the mechanism of ACD in the disease. The purpose of this study is to investigate the role of cytokines on nitric oxide-mediated apoptosis in erythroid progenitor cells of ACD in RA patients. Erythroid progenitor cells from healthy subjects and RA patients with ACD were treated with cytokines like interleukin-1β, tumor necrosis factor-α, and interferon-γ at concentrations of 2, 20, and 40 ng/ml for 14 days. Cell viability and cell apoptosis were analyzed by trypan blue staining and flow cytometry, respectively. The results showed that the highest effect of cytokines on reduction cell viability and induction cell apoptosis was found in 20 ng/ml IFN-γ-treated cells of RA patients. In addition, IFN-γ showed significantly increased nitric oxide production and iNOS mRNA expression, which was measured by Griess assay and real-time PCR, respectively. The percentage of cell apoptosis and NO production was reduced after an inducible nitric oxide synthase inhibitor, SMT, treatment. In conclusion, IFN-γ could induce nitric oxide production-mediated apoptosis process, which might be involved in the pathogenesis of ACD in RA patients.
24072605 Mechanistic insights from animal models of psoriasis and psoriatic arthritis. 2013 Nov Psoriasis and psoriatic arthritis are common chronic inflammatory conditions associated with substantial local and systemic morbidity. The genetic and phenotypic heterogeneity of these disorders presents great challenges to investigators of disease mechanisms. Valid and reliable animal models that combine the main elements of human skin and joint disease have not been developed, and this has hindered our ability to understand the complex immunopathology and develop treatments. Recently, novel animal models have been developed with the potential to greatly increase our knowledge of important mechanisms that underlie psoriatic skin and joint inflammation and bone remodeling. Herein, we discuss how recent models generated by use of promising new technologies are revealing novel inflammatory pathways that have promising therapeutic potential.
24145083 Disparate effects of anti-TNF-α therapies on measures of disease activity and mediators o 2013 BACKGROUND: Asymmetric dimethylarginine (ADMA) is associated with endothelial injury. Increased ADMA levels are found in rheumatoid arthritis (RA) and ankylosing spondylitis (AS). We set out to assess the ADMA and symmetric dimethylarginine (SDMA) levels in AS, RA, and healthy controls, and in the anti-TNF treated patients with active AS. METHODS: In 78AS patients and 29 RA patients who were anti-TNF treatment naive at baseline, along with 23 healthy control subjects, we assessed erythrocyte sedimentation rate (ESR), high-sensitivity C-reactive protein (hsCRP), ADMA, and SDMA. For AS patients, the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), back pain VAS and patient's global activity of disease were calculated. After 6 months, we repeated the assessment in 30 out of the 78 AS patients in whom the anti-TNF treatment was initiated. RESULTS: The baseline mean (SD) plasma ADMA concentration of AS patients was 0.64 (0.19) μmol/l and did not differ from controls (0.65 [0.19] μmol/l, p > 0.05). In the RA group, ADMA concentration was higher than in controls (0.77 vs. 0.65 μmol/l, p < 0.05). Both at baseline and at follow-up, ADMA levels correlated positively with BASDAI (R = 0.52, p = 0.02, and R = 0.47, p = 0.04, baseline and follow-up, respectively). Six months of anti-TNF treatment did not influence ADMA concentration (0.51 [0.12] vs. 0.51 [0.11] μmol/l, p = 0.70). CONCLUSION: An absence of changes in plasma ADMA levels in the anti-TNF treated AS group despite the improvement in disease activity (BASDAI) and inflammation (ESR, CRP) may suggest either a lack of effect, or, even if such an effect were to take place, it needs not imply measurable changes in blood ADMA.
24362356 Reverse cholesterol transport fluxes. 2014 Feb PURPOSE OF REVIEW: Reverse cholesterol transport (RCT) is considered a significant component of the atheroprotective effects of HDL. Methods for quantifying flux through the RCT pathway have not been available until recently. There is a need to improve our understanding of HDL function, including the role of RCT in general and individual steps of RCT in particular, on atherosclerosis. This review highlights new information about cholesterol flux through the RCT pathway. RECENT FINDINGS: Recent clinical studies have demonstrated several important quantitative features of cholesterol fluxes in vivo, providing insight into variability and control of specific components of the RCT pathway. The findings illustrate the independent nature of individual steps in the RCT pathway and their apparently weak relationship to plasma HDL cholesterol levels. Nonclinical studies provide some mechanistic data re-enforcing the importance of apoB particles in RCT and role roles for serum albumin and erythrocytes in free cholesterol flux. These findings suggest that the HDL-centric view of RCT may need revision. SUMMARY: The constellation of known lipoproteins and other players involved in this pathway continues to increase. Further research, particularly in humans, is needed in order to understand which parts of the RCT pathway are most relevant to the pathophysiology and treatment of atherosclerosis.
24943033 [Prevalence and significance of immunoglobulin G-anti-cyclic citrullinated peptide antibod 2014 Jun 18 OBJECTIVE: To investigate the prevalence and significance of IgG-anti-cyclic citrullinated peptides (CCP) antibody in PSS patients. METHODS: A total of 120 patients diagnosed with PSS were investigated in the first affiliated hospital of Baotou Medical College from March 2006 to December 2009. IgG-anti-CCP antibody was assayed by enzyme-linked immunosorbent assay (ELISA), also anti-Sjogren's syndrome type A (SSA) and Sjogren's syndrome type B (SSB) antibody were assayed by immunoblotting. Erythrocyte sedimentation rate (ESR) was assayed by westergren in serum, and C reactive protein (CRP), IgA, IgM, IgG and IgM-RF were detected by immune turbidimetric. At the same time, clinical symptoms and involvement of important organs were observed. Following up the patients above 3 years, the primary Sjogren's syndrome (PSS) patients who had progressed to rheumatoid arthritis (RA) were evaluated. RESULTS: The positive rate of anti-CCP antibody in the PSS patients was 19.17%; After 3 years, more patients who were positive for anti-CCP antibody had progressed to RA (χ² = 5.015,P=0.022) than the patients in negative group; The patients in anti-CCP antibody positive group were more prone to joint involvement (χ² = 8.058,P<0.05), more swollen joints (U=152.00, P<0.05) and longer morning stiffness (U=100.00, P<0.05) than the patients with negative anti-CCP antibody, but the involvement of vital organs in the two groups had no significant difference (χ² = 0.208,0.099,0.000 and 0.122, P>0.05); The positive rate of anti-SSA and SSB antibody in anti-CCP antibody positive group and negative group had no significant difference (χ² = 0.008 and 0.56, P>0.05); Multiple linear regression showed that the level of anti-CCP antibody was positively correlated with IgM-RF levels in the PSS patients (B=0.61, 95% CI=0.36-0.86, P<0.05), but had no significant correlation with ESR, CRP, IgA, IgM and IgG levels (P>0.05).There were no significant differences in the level of ESR, CRP, IgA, IgM and IgG between anti-CCP antibody positive group and negative group (P>0.05), but the level of IgM-RF in anti-CCP antibody positive group was significantly higher than that in the negative group (U=623.50, P<0.05). CONCLUSION: Positive rate of IgG-anti-CCP antibody in PSS is 19.17%, also it is associated with joint involvement and more prone to progressing to RA.