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ID PMID Title PublicationDate abstract
16855162 Cytokines and pregnancy in rheumatic disease. 2006 Jun Cytokines are important mediators involved in the successful outcome of pregnancy. The concept of pregnancy as biased toward a Th2 immune response states that Th1 type cytokines are associated with pregnancy failure and that Th2 cytokines are protective and counteract pregnancy-related disorders. Studies at the level of the maternal-fetal interface, in the maternal circulation and in cells of peripheral blood have shown that the Th2 concept of pregnancy is an oversimplification. Both Th1 and Th2 type cytokines play a role at different stages of pregnancy and are adapted to the localization and function of cells and tissues. The changes of local and systemic cytokine patterns during pregnancy correspond to neuroendocrine changes with hormones as powerful modulators of cytokine expression. Several autoimmune disorders show a modulation of disease activity during and after pregnancy. In rheumatic diseases with a predominance of a Th1 immune response, a shift to a Th2 type immune response during pregnancy has been regarded as beneficial. Studies of pregnant patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have shown a cytokine expression similar to that found in healthy pregnant women. Significant differences were present only for a few cytokines and seemed related to the activity of the underlying disease. Interestingly, a gestational increase of cytokine inhibitors interleukin 1 receptor antagonist (IL-1ra) and soluble tumor necrosis factor receptor (sTNFR) in the circulation corresponded to low disease activity in RA. The influence of hormones and cytokines on autoimmune disease is an issue for further study.
16781528 Does religious activity improve health outcomes? A critical review of the recent literatur 2005 May OBJECTIVE: Many Americans use religious activity to cope with stressful life events. Our goal was to review systematically the recent medical literature to assess the role of religion in health outcomes. DATA SOURCES: We conducted a comprehensive literature search using MEDLINE to identify studies published in the English language between January 1999 and June 2003 describing the effect of religion on health outcomes. The search strategy used the medical subject headings (MeSH) of religion; religion AND medicine; religion OR intercessory prayer; prayer; prayer therapy; religious rites; faith; medicine, traditional; religiosity; religion AND psychology; and religion AND health. STUDY SELECTION: Religious, but not spiritual, interventions were selected for inclusion. Thus, papers describing interventions such as yoga, meditation, acupuncture, and qigong were excluded. Manuscripts describing randomized controlled trials, clinical trials, and partnerships with faith-based organizations were included. DATA EXTRACTION: We found five randomized controlled trials, four clinical trials, and seven faith-based partnerships that describe the impact of religious intervention on health outcomes. Papers were analyzed by four reviewers using a modified Delphi technique to reach consensus. DATA SYNTHESIS: Religious intervention such as intercessory prayer may improve success rates of in vitro fertilization, decrease length of hospital stay and duration of fever in septic patients, increase immune function, improve rheumatoid arthritis, and reduce anxiety. Frequent attendance at religious services likely improves health behaviors. Moreover, prayer may decrease adverse outcomes in patients with cardiac disease. CONCLUSIONS: Religious activity may improve health outcomes.
16781194 From willow bark to peptides: the ever widening spectrum of NF-kappaB inhibitors. 2006 Aug Inflammation disorders such as rheumatoid arthritis, asthma and inflammatory bowel disease can be considered as 'gene expression' diseases in which the pro-inflammatory gene program of the organism is aberrantly activated. Over the past 20 years, great attention has been given to the transcription factor nuclear factor-kappaB (NF-kappaB) for its involvement in inflammatory and immune diseases. Recently, several studies have been devoted to the development of new molecules that can prevent the expression of inflammatory genes by targeting NF-kappaB pathways. Therefore, it is possible to hypothesize that these molecules might represent the future class of drugs for the treatment of inflammatory diseases.
16778421 Could Jessner's lymphocytic infiltrate of the skin be a dermal variant of lupus erythemato 2006 BACKGROUND AND OBJECTIVE: The objective of this study was to evaluate the relationship between Jessner's lymphocytic infiltration of the skin (JLI) and lupus erythematosus (LE), which has been the subject of debate since its initial description in 1953. MATERIAL AND METHODS: This is a retrospective study including all patients with a histopathologically ascertained diagnosis of JLI performed at the Laboratoire d'Histopathologie Cutanée of the Strasbourg University Hospital between 1993 and 2003. Information about patient characteristics and follow-up data were retrieved between 2004 and 2005. Special attention was paid to features indicative of LE. RESULTS: 210 consecutive patients (102 women and 108 men) with a mean age 42 years were diagnosed with JLI in the reference period. 175 patients (83%) had multiple lesions and 32 patients (15%) had only a single lesion at the time of diagnosis (data not available in 3 patients). The head, neck and upper part of the thorax were involved in 171 patients (81%). An annular or arciform configuration and/or arrangement were present in 111 patients (53%). Lesions consisted of red (100%) papules or plaques (98%). Mean follow-up was 4 years. Sixteen patients (7.6%) had proven LE. Only 2 patients (1%) developed >4 ACR criteria of systemic LE. Furthermore, 1 patient had antiphospholipid antibody syndrome and 2 patients had rheumatoid arthritis. CONCLUSIONS: This high frequency of patients with typical features of LE strongly argues that JLI could be a dermal variant of LE and not an autonomous entity. It might be the cutaneous marker of a subset of LE patients with excellent prognosis.
16546242 Epidemiology of disease risks in relation to vitamin D insufficiency. 2006 Sep Vitamin D from ultraviolet-B (UVB) irradiance, food, and supplements is receiving increased attention lately for its role in maintaining optimal health. Although the calcemic effects of vitamin D have been known for about a century, the non-calcemic effects have been studied intently only during the past two-three decades. The strongest links to the beneficial roles of UVB and vitamin D to date are for bone and muscle conditions and diseases. There is also a preponderance of evidence from a variety of studies that vitamin D reduces the risk of colon cancer, with 1000 IU/day of vitamin D or serum 25-hydroxyvitamin D levels >33 ng/mL (82 nmol/L) associated with a 50% lower incidence of colorectal cancer. There is also reasonable evidence that vitamin D reduces the risk of breast, lung, ovarian, and prostate cancer and non-Hodgkin's lymphoma. There is weaker, primarily ecologic, evidence for the role of vitamin D in reducing the risk of an additional dozen types of cancer. There is reasonably strong ecologic and case-control evidence that vitamin D reduces the risk of autoimmune diseases including such as multiple sclerosis and type 1 diabetes mellitus, and weaker evidence for rheumatoid arthritis, osteoarthritis, type 2 diabetes mellitus, hypertension and stroke. It is noted that mechanisms whereby vitamin D exerts its effect are generally well understood for the various conditions and diseases discussed here.
16539302 Eosinophilic angiocentric fibrosis of the sinonasal tract in a male patient with chronic b 2006 Jan BACKGROUND: Eosinophilic angiocentric fibrosis (EAF) is an uncommon inflammatory fibrosing lesion involving the upper respiratory mucosa, occurring mainly in young to middle aged women (female/male ratio = 2:1). The etiology is unknown; however, severalfactors might play a role in the development of EAF. Among them are prior nasal trauma (in most of the reported cases nasal surgery had been performed afew years prior to diagnosis) and inflammatory or autoimmune etiology (suggested by the ratio and the fact that in many of the reported cases a history of nonspecific allergy was found). METHODS: We report the first case of EAF affecting a male patient who also suffered from chronic inflammatory bowel disease and rheumatic fever. RESULTS: The patient underwent a diagnostic biopsy of his nasal lesion via an open rhinoplasty approach, with the resulting diagnosis of EAF. Despite the fact that the literature does not show advantages to any specific therapy, the patient elected to remain under observation. During a two-year follow-up period, there is no evidence of progression of disease. CONCLUSION: The presence of concomitant rheumatoid arthritis and chronic inflammatory bowel disease in our patient, as well as the fact that nine previously reported cases of EAF had allergic/immune symptoms, raise the possibility that inflammatory or autoimmune factors may have a role in the development of this unusual pathological entity.
16522339 De novo design TNF-alpha antagonistic peptide based on the complex structure of TNF-alpha 2006 Aug 20 Tumor necrosis factor-alpha (TNF-alpha) antagonists have become therapeutic drugs for immunological diseases including rheumatoid arthritis, inflammatory bowel disease, Crohn's disease, etc. Low molecular weight synthetic peptides can mimic the binding sites of TNF-alpha receptors and block the activity of TNF-alpha. Based on the 3-D complex structure of TNF-alpha with its neutralizing monoclonal antibody (Mab) Z12, an antagonistic peptide (AP) was rationally de novo designed. The designed AP possessed similar structural character and potential bioactivity with Mab Z12. AP could competitively inhibit the binding of Mab Z12 to TNF-alpha, TNF-alpha-meditated caspase activation and TNF-alpha-induced cytotoxicity on murine L929 cells with a dose-dependent fashion. This study highlights the potential of computation-aided method for the design of novel peptides with the ability to block the deleterious biological effects of TNF-alpha.
16503422 Statins: potential new indications in inflammatory conditions. 2006 Apr Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are potent cholesterol-lowering drugs. In addition to their cholesterol-lowering properties, statins exert a number of so-called 'pleiotropic', vasculoprotective actions that include improvement of endothelial function, increased nitric oxide (NO) bioavailability, antioxidant properties, stabilisation of atherosclerotic plaques, regulation of progenitor cells, inhibition of inflammatory responses and immunomodulatory actions. Pleiotropic actions of statins may have potential clinical impact in vascular disease beyond cholesterol lowering. The ongoing Justification for the Use of statins in Primary prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER), for example, tests the effects of statins in the primary prevention of cardiovascular disease among patients with low levels of low-density lipoprotein cholesterol (LDL-C) and elevated high-sensitivity C-reactive protein (hs-CRP). Additionally, previous studies have shown that although cholesterol is not an established stroke risk factor, statin therapy is associated with a reduction in the incidence of strokes. It is known that sudden withdrawal of statin treatment may acutely impair vascular function and increase morbidity and mortality in patients with vascular disease. Furthermore, the anti-inflammatory effects of statins may have clinical impact in a number of non-vascular conditions including multiple sclerosis and rheumatoid arthritis.
16501917 Long-term persistence of both functional and non-functional alleles at the leukocyte immun 2006 May The leukocyte immunoglobulin-like receptor (LILR) family consists of 13 loci, and a number of variations have been identified in these genes. Some polymorphisms of the LILR genes are reported to be associated with susceptibility to diseases such as rheumatoid arthritis and multiple sclerosis. LILRA3, one of the LILR genes, exhibits a presence or absence variation due to a 6.7-kb deletion in various populations. In this study, variation screening of the LILRA3 gene revealed high allele frequency of the 6.7-kb LILRA3 deletion (71%) in Japanese, in contrast to the frequency reported for the other populations. In addition, we identified a splice acceptor mutation in intron 1 with allele frequency of 19%, resulting in three alternatively spliced isoforms. Surprisingly, all of these isoforms were found to contain premature termination codons (PTCs) in the exon 3. Taken together, approximately 80% of Japanese lack functional LILRA3 alleles. The maximum likelihood coalescent analysis suggested that two major lineages, functional alleles and PTC-containing alleles, have been maintained for 2.75 million years in humans. These results prompted us to hypothesize that balancing selection had maintained both the functional and non-functional alleles at the LILRA3 locus. This hypothesis is consistent with the observation that the 6.7-kb LILRA3 deletion is detected worldwide in the presence of functional LILRA3 alleles.
16403848 Mycophenolate mofetil treatment of myasthenia gravis. 2006 Feb OBJECTIVE: To review published literature evaluating the effectiveness of mycophenolate mofetil for the treatment of myasthenia gravis (MG). DATA SOURCES: Searches of MEDLINE (1966-August 2005) and Cochrane Database (1993-August 2005) were conducted. Studies conducted in humans and published in English were retrieved. Additional data were identified through subsequent bibliographic reviews. DATA SYNTHESIS: Interruption of T- and B-lymphocyte proliferation in various autoimmune diseases has been investigated. Mycophenolate is known to inhibit lymphocyte proliferation and has shown improved clinical responses in several autoimmune diseases including lupus erythematosus, rheumatoid arthritis, and systemic vasculitis. Data suggesting similar benefits in MG treatment have been reported in case reports, retrospective analyses, an open-label trial, and a randomized, double-blind trial. CONCLUSIONS: Limited evidence from retrospective analyses and clinical trials suggests that mycophenolate is a possible treatment option for patients with MG. Improvement in clinical symptoms and a steroid-sparing effect have been reported when mycophenolate is used in this patient population. Larger, randomized, controlled, and comparative trials are needed to establish optimal dose, time to effect, specific therapeutic role, and long-term safety for mycophenolate when used for treating MG.
16388320 Distribution pattern of tenascin-C in glioblastoma: correlation with angiogenesis and tumo 2005 Tenascin-C (TN-C) is an extracellular matrix protein which participates in different processes like normal fetal development, wound healing, inflammation, keloids and rheumatoid arthritis. Furthermore, the immunostaining for TN-C is seen in the stroma of various malignant tumors as in glioblastoma multiforme (GBM), however, the significance of these findings is still not clear. In this study 62 GBM samples were analyzed immunohistochemically for distribution patterns of TN-C and correlated with angiogenesis and tumor cell proliferation. Tenascin-C in GBM localizes in two compartments, perivascular and intercellular space. Intercellular tenascin-C (TN-C ic) showed focal distribution in 66%, and diffuse one in 34% of cases. Perivascular tenascin-C (TN-C pv) showed strong correlation with microvascular density (MVD) and vascular endothelial growth factor (VEGF) expression. Moreover, it seems that TN-C pv enhanced the effect of VEGF. Intercellular TN-C did not correlate with MVD and VEGF expression, but showed strong correlation with proliferation index. Furthermore, tumors with diffuse TN-C ic expression had higher proliferation indices than tumors with focal TN-C expression. Our results indicate that TN-C plays a role in angiogenesis and tumor cell proliferation, but beside the intensity of expression, the distribution patterns are also important in these processes. This study also suggests that perivascular and intercellular TN-C compartments have probably different sources and different roles in GBM.
16369754 Nonsteroidal anti-inflammatory drugs (NSAIDs) in the perioperative phase in traumatology a 2005 Dec OBJECTIVE: To achieve analgesic, anti-inflammatory and antipyretic effects in traumatology and orthopedic surgery without side effects or with the least possible side effects, with special emphasis on bone healing. INDICATIONS: Acute and chronic inflammatory conditions, e. g., rheumatoid arthritis, ankylosing spondylitis. Degenerative joint disease. Posttraumatic and postoperative pain, edema, or fever. Prevention of heterotopic bone formation. CONTRAINDICATIONS: Hypersensitivity. Gastrointestinal ulceration or bleeding. Severe hepatic or renal impairment. RESULTS: Nonsteroidal anti-inflammatory drugs (NSAIDs) are invaluable in treating a variety of musculoskeletal conditions. As well as their excellent analgesic potency their anti-inflammatory effects are beneficial in treating posttraumatic and postoperative edema. In addition, NSAIDs inhibit heterotopic bone formation after hip arthroplasty. Animal studies, however, have demonstrated that they cause delayed fracture healing. Although clinical studies have not yet supplied unequivocal evidence of this effect in human subjects, the authors recommend that in the presence of other risk factors which may adversely affect fracture healing, such as smoking, diabetes mellitus or peripheral arterial occlusive disease, the indication of NSAID use for analgesia should be strictly limited. Therapeutic alternatives such as centrally acting agents (e. g., weak opioids) should be considered in these patients.
16355451 Effects of the extract of a Chinese herb Tripterygium wilfordii hook f on rat pituitary gl 2005 In China, the ethylacetate extract of the herb Tripterygium wilfordii Hook f (TWEE), containing the major active ingredient triptolide, is often used with favorable effect on rheumatoid arthritis patients, in alternation with the use of prednisone. The mechanism of this therapeutic effect, however, has not been completely delineated. In this study, we studied how TWEE and prednisone affect the pituitary and adrenal glands in rats. Thirty normal male Sprague-Dawley rats (ten per group) were randomly assigned to receive: (1) TWEE (25 mg/kg, twice a day), (2) prednisone (2 mg/kg, twice a day), or (3) vehicle (control) (0.5% sodium carboxymethyl cellulose 1 ml, twice a day), orally for 30 days. Pituitary and trunk blood were collected on day 31. Adrenocorticotropic hormone (ACTH) expression in the pituitary gland was assessed morphologically by immunohistochemical techniques. Plasma ACTH concentrations and serum corticosterone concentrations were quantitatively measured by radioimmunoassay. We found that TWEE significantly increased plasma ACTH concentration and serum corticosterone concentration and dramatically increased the number of ACTH-positive cells in the pituitary. Our findings indicate that TWEE can promote the synthesis and secretion of ACTH cells--in the pars distalis of the rat pituitary gland and the production of corticosterone in the zone fasciculata of the adrenal cortex. Our results indicate that TWEE has a cortical hormone-like function and can promote adrenal cortex function by activating the hypothalamus-pituitary-adrenal axis.
16269393 Production, purification and characterisation of recombinant Fahsin, a novel antistasin-ty 2005 Nov Serine proteinases from inflammatory cells, including polymorphonuclear neutrophils, are involved in various inflammatory disorders, like pulmonary emphysema and rheumatoid arthritis. Inhibitors of these serine proteinases are potential drug candidates for the treatment of these disorders, since they prevent the unrestricted proteolysis. This study describes a novel specific antistasin-type inhibitor of neutrophil serine proteinases, we called Fahsin. This inhibitor was purified from the Nile leech Limnatis nilotica, sequenced and heterologously expressed using a synthetic gene in the methylotrophic yeast Pichia pastoris, yielding 0.5 g(-l) of the protein in the culture medium. Recombinant Fahsin was purified to homogeneity and characterised by N-terminal amino acid sequencing and mass spectrometry. Inhibition-kinetic analysis showed that recombinant Fahsin is a fast, tight-binding inhibitor of human neutrophil elastase with inhibition constant in the nanomolar range. Furthermore, recombinant Fahsin was, in contrast to various other neutrophil elastase inhibitors, insensitive to chemical oxidation and biological oxidation via myeloperoxidase-generated free oxygen radicals. Thus, Fahsin constitutes a novel member of a still expanding family of naturally occurring inhibitors of serine proteinases with potential therapeutic use for treatment of human diseases.
16193356 Development and reliability of a standard rating system for outcome measurement of foot an 2005 Sep BACKGROUND: The aim of this study was to report the five scales comprising the rating system that the Japanese Society for Surgery of the Foot (JSSF) devised (JSSF standard rating system) and the newly offered interpretations and criteria for determinations of each assessment item. METHODS: We produced the new scales for the JSSF standard system by modifying the clinical rating systems established by the American Orthopaedic Foot and Ankle Society (AOFAS scales) and the Japanese Orthopaedic Association's foot rating scale (JOA scale). We also provided interpretations of each assessment item and the criteria of determinations in the new standard system. RESULTS: We improved the ambiguous expressions and content in the conventional standard rating systems so they would be easily understood by Japanese people. The result was five scales in total. Four were designed for use specifically for ankle-hindfoot, midfoot, hallux metatarsophalangeal-interphalangeal, and lesser metatarsophalangeal-ineterphalangeal sites; and the fifth was for the foot and ankle with rheumatoid arthritis. Furthermore, we described interpretations and criteria for determinations with regard to evaluation items in each scale. CONCLUSIONS: Conventionally, the AOFAS scales or the JOA scale have been separately applied depending on the sites or disorders concerned, but it was often difficult to decide on scores during practical evaluations because of differing expressions in different languages and also because of ambiguity in the interpretation of each evaluation item and in scoring standards as well. JSSF improved these scales and added definite interpretations of evaluation items as well as criteria for the rating (to be reported here in part I). Because these steps were expected to improve the reliability of outcomes assessed by each scale, we examined the reliability in scores of the newly developed scales, which are reported in part II (in this issue).
16117705 Prospects for a T-cell receptor vaccination against myasthenia gravis. 2005 Aug T-cell receptor (TCR) vaccination has been proposed as a specific therapy against autoimmune diseases. It is already used in clinical trials, which are supported by pharmaceutical companies for the treatment of multiple sclerosis, rheumatoid arthritis and psoriasis. Current vaccine developments are focusing on enhancement of immunogenicity as well as selecting the best route of immunization and adjuvant to favor the therapeutic effect. In the meantime, academic laboratories are tackling the regulatory mechanisms involved in the beneficial effect of the vaccines to further understand how to control the therapeutic tool. Indeed, several examples in experimental models of autoimmune diseases indicate that any specific therapy may rely on a delicate balance between the pathogenic and regulatory mechanisms. This review presents a critical analysis of the potential of such therapy in myasthenia gravis, a prototype antibody-mediated disease. Indeed, a specific pathogenic T-cell target population and a TCR-specific regulatory mechanism mediated by anti-TCR antibodies and involved in protection from the disease have recently been identified in a patient subgroup. The presence of spontaneous anti-TCR antibodies directed against the pathogenic T-cells that may be boosted by a TCR vaccine provides a rationale for such therapy in myasthenia gravis. The development of this vaccine may well benefit from experience gained in the other autoimmune diseases in which clinical trials are ongoing.
16095585 CFSUM1 and CFSUM2 in urine from patients with chronic fatigue syndrome are methodological 2006 Feb McGregor et al. reported increased levels of an unidentified urinary compound (CFSUM1) in patients with chronic fatigue syndrome (CFS), with reduced excretion of another unidentified compound (CFSUM2), and suggested the possibility of chemical or metabolic 'markers' for CFS. The identity of CFSUM1 as reported was erroneous and the identities of these compounds have remained unknown until now. Urine samples were obtained from 30 patients with ME/CFS, 30 age- and sex-matched healthy controls, 20 control patients with depression and 22 control patients with rheumatoid arthritis. Samples were prepared using the published methods of McGregor et al. to produce heptafluorobutyryl-isobutyl derivatives of urinary metabolites. Alternative preparations utilised isopropyl, n-butyl and trifluoroacetyl derivatives. These were separated and identified using gas chromatography-mass spectrometry. CFSUM2 was identified as being partially derivatised [isobutyl ester-mono-heptafluorobutyryl (HFB)] serine. CFSUM1 was identified as partially derivatised pyroglutamic acid, being the isobutyl ester without formation of a HFB derivative. Both CFSUM1 and CFSUM2 are artefacts of the sample preparation procedure and previously reported quantitative abnormalities of CFSUM1 and CFSUM2 in urine from patients with ME/CFS are also artefactual. Pyroglutamic acid may be of primarily dietary origin. The methods used cannot provide reliable qualitative or quantitative data on urinary metabolites. No clinical or biochemical significance can be drawn between these compounds in ME/CFS or any other clinical conditions.
15992788 Urinary and plasma organic acids and amino acids in chronic fatigue syndrome. 2005 Nov Previous work by others have suggested the occurrence of one or more chemical or metabolic 'markers' for ME/CFS including specific amino acids and organic acids and a number of unidentified compounds (CFSUM1, CFSUM2). We have shown elsewhere that CFSUM1 is partially derivatised pyroglutamic acid and CFSUM2 partially derivatised serine and have suggested and demonstrated that the analytical methods used were unsuitable to identify or to accurately quantify urinary metabolites. We have now made a detailed analysis of plasma and urinary amino acids and of urinary organic acids from patients with ME/CFS and from three control groups. Fasting blood plasma and timed urine samples were obtained from 31 patients with CFS, 31 age and sex-matched healthy controls, 15 patients with depression and 22 patients with rheumatoid arthritis. Plasma and urinary amino acids and urinary organic acids were determined using established and validated methods and data compared by statistical analysis. None of the previously reported abnormalities in urinary amino acids or of organic acids could be confirmed. Results however provide some evidence in patients with ME/CFS for underlying inflammatory disease and for reduced intramuscular collagen with a lowered threshold for muscle micro-injury. These factors in combination may provide a basis for the fatigue and muscle pain that are the major symptoms in these patients.
15660456 Genetic studies in the rheumatic diseases: present status and implications for the future. 2005 Jan Recent breakthroughs in genetic methodology have greatly augmented our understanding of the contribution of genetics to susceptibility to the rheumatic diseases. Disorders in which familial aggregation has been best documented include rheumatoid arthritis (RA), ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), and systemic sclerosis (SSc). Much of the genetic contribution to these diseases lies in the MHC, including HLA-DR4 (RA), HLA-B27 (AS), HLA-DRB1*0301, DRB1*1501/*1503, DRB1*08, and C4 null alleles (SLE), and HLA-DRB1*11 and DRB1*1502 (SSc). Genome-wide scans have provided inconsistent data in RA, although consistent regions have been observed in scans from different groups in AS and SLE. No consistent non-MHC candidate gene has been identified in RA. There is active investigation in AS in this area. In SLE the Fc gamma RIIa and Fc gamma IIIa genes have been most thoroughly described, and in SSc fibrillin and SPARC. Newer techniques being developed presently, such as high density single nucleotide polymorphism genome-wide scanning, show promise to bring these analyses to the next level, which will hopefully result not only in better screening of individuals at highest risk, but also in novel treatments.
15607729 No inhibition of IL-27 signaling by soluble gp130. 2005 Jan 28 Soluble gp130 is the natural inhibitor of trans-signaling mediated by the soluble IL-6/IL-6R complex. In mouse models, recombinant sgp130 has been successfully applied for the treatment of diseases that are triggered and maintained by soluble IL-6R like Crohn's disease, peritonitis, rheumatoid arthritis, and colon cancer. The novel heterodimeric cytokine IL-27 (p28/EBV-induced gene 3) has been shown to act via a heterodimeric receptor complex of gp130 and the WSX-1 receptor, and to co-regulate the Th(1) immune response after infection. Therefore, we have tested the potential of the recombinant sgp130-Fc protein to also inhibit signaling-mediated IL-27. Here we show that sgp130-Fc does not interfere with IL-27 signaling. We therefore conclude that IL-27 does not bind with high affinity to gp130.