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1.  Immediate determination of ACPA and rheumatoid factor - a novel point of care test for detection of anti-MCV antibodies and rheumatoid factor using a lateral-flow immunoassay 
Arthritis Research & Therapy  2010;12(3):R120.
Introduction
Autoantibodies against mutated and citrullinated vimentin (MCV) represent a novel diagnostic marker for rheumatoid arthritis (RA). Recently, an increased sensitivity for anti-MCV compared to autoantibodies against cyclic citrullinated peptides (anti-CCP2) was shown in cohorts of patients with early RA and established disease.
The aim of this study was to develop and evaluate a point of care test (POCT) for detection of anti-MCV antibodies immediately at the first visit or at the bed side.
Methods
A lateral-flow immunoassay was developed for simultaneous detection of anti-MCV antibodies and rheumatoid factor (RF-IgG) and evaluated in a prospective setting. Analyses were performed from whole blood samples of patients with seropositive RA (n = 108), seronegative RA as well as other rheumatic disorders (n = 122), and healthy blood donors (n = 200) and compared to detection via ELISA.
Results
Using the POCT, anti-MCV antibodies were detected in 54.6% and RF-IgG in 56.5% of patients with RA. Specificity was 99.1% for anti-MCV antibodies and 91.2% for RF-IgG. Compared to ELISA's results, POCT sensitivity was 69.3% for anti-MCV and 55.6% for RF-IgG, specificity was 99.7% and 97.2%, respectively.
Conclusions
This POCT for detection of anti-MCV antibodies and RF-IgG provides high specificity for the diagnosis of RA and is useful in clinical practice due to its simplicity and its reliable performance. This test can greatly improve a timely management of RA and may help in screening patients with suspected RA in non-specialized settings prompting early referrals.
doi:10.1186/ar3057
PMCID: PMC2911914  PMID: 20569500
2.  SiPaGene: A new repository for instant online retrieval, sharing and meta-analyses of GeneChip® expression data 
BMC Genomics  2009;10:98.
Background
Microarray expression profiling is becoming a routine technology for medical research and generates enormous amounts of data. However, reanalysis of public data and comparison with own results is laborious. Although many different tools exist, there is a need for more convenience and online analysis with restriction of access and user specific sharing options. Furthermore, most of the currently existing tools do not use the whole range of statistical power provided by the MAS5.0/GCOS algorithms.
Description
With a current focus on immunology, infection, inflammation, tissue regeneration and cancer we developed a database platform that can load preprocessed Affymetrix GeneChip expression data for immediate access. Group or subgroup comparisons can be calculated online, retrieved for candidate genes, transcriptional activity in various biological conditions and compared with different experiments. The system is based on Oracle 9i with algorithms in java and graphical user interfaces implemented as java servlets. Signals, detection calls, signal log ratios, change calls and corresponding p-values were calculated with MAS5.0/GCOS algorithms. MIAME information and gene annotations are provided via links to GEO and EntrezGene. Users access via https protocol their own, shared or public data. Sharing is comparison- and user-specific with different levels of rights. Arrays for group comparisons can be selected individually. Twenty-two different group comparison parameters can be applied in user-defined combinations on single or multiple group comparisons. Identified genes can be reviewed online or downloaded. Optimized selection criteria were developed and reliability was demonstrated with the "Latin Square" data set. Currently more than 1,000 arrays, 10,000 pairwise comparisons and 500 group comparisons are presented with public or restricted access by different research networks or individual users.
Conclusion
SiPaGene is a repository and a high quality tool for primary analysis of GeneChips. It exploits the MAS5.0/GCOS pairwise comparison algorithm, enables restricted access and user specific sharing. It does not aim for a complete representation of all public arrays but for high quality analysis with stepwise integration of reference signatures for detailed meta-analyses. Development of additional tools like functional annotation networks based on expression information will be future steps towards a systematic biological analysis of expression profiles.
doi:10.1186/1471-2164-10-98
PMCID: PMC2657156  PMID: 19265543
3.  Cells of the synovium in rheumatoid arthritis. Macrophages 
The multitude and abundance of macrophage-derived mediators in rheumatoid arthritis and their paracrine/autocrine effects identify macrophages as local and systemic amplifiers of disease. Although uncovering the etiology of rheumatoid arthritis remains the ultimate means to silence the pathogenetic process, efforts in understanding how activated macrophages influence disease have led to optimization strategies to selectively target macrophages by agents tailored to specific features of macrophage activation. This approach has two advantages: (a) striking the cell population that mediates/amplifies most of the irreversible tissue destruction and (b) sparing other cells that have no (or only marginal) effects on joint damage.
doi:10.1186/ar2333
PMCID: PMC2246244  PMID: 18177511
4.  Decrease in expression of bone morphogenetic proteins 4 and 5 in synovial tissue of patients with osteoarthritis and rheumatoid arthritis 
Bone morphogenetic proteins (BMPs) have been identified as important morphogens with pleiotropic functions in regulating the development, homeostasis and repair of various tissues. The aim of this study was to characterize the expression of BMPs in synovial tissues under normal and arthritic conditions. Synovial tissue from normal donors (ND) and from patients with osteoarthritis (OA) and rheumatoid arthritis (RA) were analyzed for BMP expression by using microarray hybridization. Differential expression of BMP-4 and BMP-5 was validated by semiquantitative RT-PCR, in situ hybridization and immunohistochemistry. Activity of arthritis was determined by routine parameters for systemic inflammation, by histological scoring of synovitis and by semiquantitative RT-PCR of IL-1β, TNF-α, stromelysin and collagenase I in synovial tissue. Expression of BMP-4 and BMP-5 mRNA was found to be significantly decreased in synovial tissue of patients with RA in comparison with ND by microarray analysis (p < 0.0083 and p < 0.0091). Validation by PCR confirmed these data in RA (p < 0.002) and also revealed a significant decrease in BMP-4 and BMP-5 expression in OA compared with ND (p < 0.015). Furthermore, histomorphological distribution of both morphogens as determined by in situ hybridization and immunohistochemistry showed a dominance in the lining layer of normal tissues, whereas chronically inflamed tissue from patients with RA revealed BMP expression mainly scattered across deeper layers. In OA, these changes were less pronounced with variable distribution of BMPs in the lining and sublining layer. BMP-4 and BMP-5 are expressed in normal synovial tissue and were found decreased in OA and RA. This may suggest a role of distinct BMPs in joint homeostasis that is disturbed in inflammatory and degenerative joint diseases. In comparison with previous reports, these data underline the complex impact of these factors on homeostasis and remodeling in joint physiology and pathology.
doi:10.1186/ar1923
PMCID: PMC1526630  PMID: 16542506
5.  Multiple functions for CD28 and cytotoxic T lymphocyte antigen-4 during different phases of T cell responses: implications for arthritis and autoimmune diseases 
Arthritis Research & Therapy  2004;6(2):45-54.
Chronic T cell responses, as they occur in rheumatoid arthritis, are complex and are likely to involve many mechanisms. There is a growing body of evidence that, in concert with the T cell antigen receptor signal, CD28 and cytotoxic T-lymphocyte antigen-4 (CTLA-4; CD152) are the primary regulators of T cell responses. Whereas CD28 primarily activates T cell processes, CTLA-4 inhibits them. The mechanism for this dichotomy is not fully understood, especially as CD28 and CTLA-4 recruit similar signalling molecules. In addition, recent studies demonstrate that CD28 and CTLA-4 have multiple functions during T cell responses. In particular, CTLA-4 exerts independent distinct effects during different phases of T cell responses that could be exploited for the treatment of rheumatoid arthritis.
doi:10.1186/ar1158
PMCID: PMC400439  PMID: 15059264
CD152; costimulation; CTLA-4Ig; inflammation; polymorphism; signal transduction
6.  Macrophages in rheumatoid arthritis 
Arthritis Research  2000;2(3):189-202.
The abundance and activation of macrophages in the inflamed synovial membrane/pannus significantly correlates with the severity of rheumatoid arthritis (RA). Although unlikely to be the 'initiators' of RA (if not as antigen-presenting cells in early disease), macrophages possess widespread pro-inflammatory, destructive, and remodeling capabilities that can critically contribute to acute and chronic disease. Also, activation of the monocytic lineage is not locally restricted, but extends to systemic parts of the mononuclear phagocyte system. Thus, selective counteraction of macrophage activation remains an efficacious approach to diminish local and systemic inflammation, as well as to prevent irreversible joint damage.
doi:10.1186/ar86
PMCID: PMC130001  PMID: 11094428
cytokine; fibroblast; macrophage; monocyte; nitric oxide; peripheral blood; reactive oxygen species; rheumatoid arthritis; synovial membrane; T-cell

Results 1-6 (6)