Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
21034650 Total knee arthroplasty using computer assisted navigation in patients with severe valgus 2010 Oct BACKGROUND: Severe valgus deformity often has bone defect and laxity of the medial ligamentous, and total knee arthroplasty in severe valgus knee is, in most cases, more challenging for surgeons. The usefulness of a computer assisted navigation system in reestablishing the mechanical axis has been well established. Hence, the interest for surgeons is how the navigation system makes the procedure of total knee arthroplasty with severe valgus knee easier. METHODS: From June 2006 to March 2008 in Department of Joint Surgery, Shanghai Sixth People's Hospital, 6 patients (7 knees) with severe valgus knee underwent total knee arthroplasty using the Stryker Navigation system, which is an active wireless and imageless system. All the patients were followed up for 12 to 18 months after surgery. The X-ray radiographs for whole limbs were obtained on all patients to determine preoperative and postoperative alignments. RESULTS: A primary, posterior stabilized prosthesis was utilized in all cases. The average preoperative overall mechanical axis of the seven knees was 19.6° ± 4.6° of valgus (range 16° to 29°), and the average postoperative mechanical axis was 0.4° ± 0.7° (range 0.8° varus to 1.4° valgus). CONCLUSIONS: The navigation system is a very effective and useful tool for accurate intraoperative restoration of alignment in the face of significant deformity with valgus knee. To prevent component malposition, we did not reduce the knee before solidification of bone cement but controlled alignment using the navigation system up to implantation of the final component.
21069420 High mobility group box 1 induces synoviocyte proliferation in rheumatoid arthritis by act 2011 Jun Recently, it was discovered that high mobility group box chromosomal protein 1 (HMGB1) acts as a potent pro-inflammatory cytokine that is released into the extracellular milieu. Signal transducer and activator of transcription (STAT) proteins play an important role in cytokine signaling. Some investigators have reported preferential activation of STAT1, and others have reported preferential activation of STAT3 in response to endogenous interleukin-6 (IL-6) in patients with rheumatoid arthritis. Here, we show that expression of the HMGB1 protein is increased in the articular tissues of collagen-induced arthritis (CIA) rats, especially in cytoplasm and extracellular, following synoviocyte proliferation and STAT1 activation. In vitro, recombined human HMGB1 induced RSC-364 cell proliferation, activated STAT1 phosphorylation, increased the expression of cyclin D1 and CDK4 protein, and decreased the expression of p21 protein. In summary, our study suggests that HMGB1 plays an important role of cytokine in the pathogenesis of RA, which possibly induces synovial cell proliferation by activating the STAT1 signal pathway.
19877027 Cancer risk in patients with rheumatoid arthritis treated with anti-tumor necrosis factor 2009 Nov OBJECTIVE: To determine the short-term and medium-term risks of cancer in patients receiving anti-tumor necrosis factor alpha (anti-TNFalpha) therapies that have proven effective in the treatment of chronic inflammatory conditions. METHODS: By linking together data from the Swedish Biologics Register, Swedish registers of RA, and the Swedish Cancer Register, we identified and analyzed for cancer occurrence a national cohort of 6,366 patients with RA who first started anti-TNF therapy between January 1999 and July 2006. As comparators, we used a national biologics-naive RA cohort (n = 61,160), a cohort of RA patients newly starting methotrexate (n = 5,989), a cohort of RA patients newly starting disease-modifying antirheumatic drug combination therapy (n = 1,838), and the general population of Sweden. Relative risks (RRs) were estimated using Cox regression analyses, examining overall RR as well as RR by time since the first start of anti-TNF therapy, by the duration of active anti-TNF therapy, and by the anti-TNF agent received. RESULTS: During 25,693 person-years of followup in 6,366 patients newly starting anti-TNF, 240 first cancers occurred, yielding an RR of 1.00 (95% confidence interval 0.86-1.15) versus the biologics-naive RA cohort, and similar RRs versus the other 2 RA comparators. RRs did not increase with increasing time since the start of anti-TNF therapy, nor with the cumulative duration of active anti-TNF therapy. During the first year following the first treatment start, but not thereafter, dissimilar cancer risks for adalimumab, etanercept, and infliximab were observed. CONCLUSION: During the first 6 years after the start of anti-TNF therapy in routine care, no overall elevation of cancer risk and no increase with followup time were observed.
19828600 Metastasis-inducing S100A4 protein is associated with the disease activity of rheumatoid a 2009 Dec OBJECTIVES: To evaluate the association between metastasis-inducing protein S100A4 and disease activity in patients with RA, and to demonstrate the effect of TNF-alpha blocking therapy on plasma levels of S100A4 in these patients. METHODS: Plasma levels of the S100A4 protein were analysed in 40 anti-TNF-alpha naive patients with active RA. Of the 40 patients, 25 were treated with adalimumab and monitored over time. The conformational form of S100A4 was analysed using size-exclusion gel chromatography. TNF-alpha mRNA expression and protein synthesis were analysed by RT-PCR and ELISA, respectively. RESULTS: Baseline levels of S100A4 were significantly correlated with disease activity in RA patients (r = 0.41; P < 0.01). After 12 weeks of treatment with adalimumab, there was an obvious shift in the conformations of S100A4 from the multimeric to the dimeric forms, whereas the total levels of the S100A4 protein remained unchanged. This suggests that the bioactive (multimer) S100A4 may decline in response to successful treatment with adalimumab. In addition, we showed significant up-regulation of TNF-alpha mRNA (P < 0.01), and protein release to the cell culture medium of monocytes stimulated with the S100A4 multimer compared with those treated with the dimer and to the unstimulated monocytes (P < 0.001). CONCLUSIONS: This is the first study to show that the levels of the S100A4 protein are correlated with RA disease activity. Furthermore, only the bioactive form, but not the total amount of S100A4, decreases after successful TNF-alpha blocking therapy in patients with RA. These data support an important role for the S100A4 multimer in the pathogenesis of RA.
20211202 Rosiglitazone reduces a wide range of proinflammatory profiles in synovial fibroblast SW98 2010 Jun 15 Rosiglitazone (RSG) has been known to play a role in the modulation of inflammatory responses. Therefore, we sought to elucidate the underlying molecular mechanism by which RSG regulates the development of rheumatoid arthritis. Firstly, we examined the preventive effect of RSG on the inflammatory mediators induced by spheroid culture of synovial sarcoma SW982. Expression of proinflammatory cytokines under spheroid culture was more elevated than that under monolayer culture while RSG abolished inflammatory responses. The upregulation of inflammation-related genes by spheroid culture was closely associated with NFkappaB (NFkappaB) activation. Also, activation of p38 and c-Jun N-terminal kinase (JNK) by spheroid culture was abrogated with RSG treatment. Lastly, it was demonstrated that RSG reduced the development of arthritis in mice immunized with collagen, improving the histology of inflamed joint. In summary, RSG reduces inflammatory responses of synovial fibroblast via not only inhibition of NFkappaB but also modulation of both p38 and JNK.
19327945 [Anti-TNF alpha in the treatment of rheumatoid arthritis and ankylosing spondylitis]. 2009 May Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are, with psoriatic arthritis, the most frequent rheumatic diseases. A better understanding of pathophysiology of these diseases had led to the development of new treatments refered as to biologic agents and, among them, TNF blocking agents have a major role. The knowledge of these drugs in terms of mechanisms of action, indications and potentials side effects has to be known to improve the efficacy/tolerance balance. Although these 3 anti-TNFalpha agents are currently used, new TNF blocking agents are under evaluation and should increase the number of drugs available within the next months.
20467180 Cytomegalovirus-induced infectious mononucleosis-like syndrome in a rheumatoid arthritis p 2010 We report a patient with rheumatoid arthritis (RA) who developed cytomegalovirus (CMV)-induced infectious mononucleosis-like syndrome (IMLS) while being treated with methotrexate and infliximab. She suddenly developed intermittent high fever and general fatigue with liver dysfunction, remarkable lymphocytosis and laboratory data suggestive of CMV reactivation. Her clinical symptoms quickly improved after the cessation of methotrexate and infliximab without the use of anti-viral drugs such as ganciclovir. CMV-induced IMLS might be a cause of persistent fever in RA patients, particularly when biologics are used for treatment.
20222108 Adiponectin stimulates prostaglandin E(2) production in rheumatoid arthritis synovial fibr 2010 Jun OBJECTIVE: Adipokines may influence inflammatory and/or immune responses. This study was undertaken to examine whether adiponectin affects the production of prostaglandin E(2) (PGE(2)) by rheumatoid arthritis synovial fibroblasts (RASFs). METHODS: Synovial tissue was obtained from patients with RA who were undergoing joint replacement surgery. Fibroblast-like cells from the third or fourth passage were used as RASFs. Expression of adiponectin receptor messenger RNA (mRNA) and protein was detected. PGE(2) (converted from arachidonic acid) was measured by enzyme-linked immunosorbent assay (ELISA). Expression of mRNA and protein for cyclooxygenase 2 (COX-2) and membrane-associated PGE synthase 1 (mPGES-1), key enzymes involved in PGE(2) synthesis, was detected in RASFs. The effects of RNA interference (RNAi) targeting the adiponectin receptor genes and the receptor signal inhibitors were examined. The influence of adiponectin on NF-kappaB activation in RASFs was measured with an ELISA kit. RESULTS: Adiponectin receptors were detected in RASFs. Adiponectin increased both COX-2 and mPGES-1 mRNA and protein expression by RASFs in a time- and concentration-dependent manner. PGE(2) production by RASFs was also increased by the addition of adiponectin, and this increase was inhibited by RNAi for the adiponectin receptor gene, or coincubation with the receptor signal inhibitors. Enhancement of NF-kappaB activation by adiponectin as well as by interleukin-1beta was observed in RASFs. CONCLUSION: Our findings indicate that adiponectin induces COX-2 and mPGES-1 expression, resulting in the enhancement of PGE(2) production by RASFs. Thus, adiponectin may play a role in the pathogenesis of synovitis in RA patients.
20511555 An autoantigen-specific, highly restricted T cell repertoire infiltrates the arthritic joi 2010 Jul 1 Although it is clear that CD4(+) T cells play a major role in mediating the pathogenesis of autoimmunity, they often represent only a minor population at the site of inflammation in autoimmune diseases. To investigate the migration and specificity of autoimmune T cells to the inflammatory site, we used the collagen-induced arthritis model to determine the frequency, clonotype, and specificity of T cells that infiltrate arthritic joints. We demonstrate that despite the fact that CD4(+) T cells are a minor population of the synovial infiltrate, the CD4(+) T cells present are a highly selective subset of the TCR repertoire and, based on CDR3 length polymorphisms, have a limited clonality. Although a similar repertoire of type II collagen (CII)-specific TCR-BV8 and BV14-expressing T cells was found in peripheral lymphoid organs, the clonality of the TCR-BV8 and BV14 T cells that migrate to the arthritic joint generally made up a single CDR3 length. T cell hybridomas produced from these joint-derived cells revealed that many of these infiltrating T cells are CII specific, and the majority recognize mouse CII. These data suggest that despite being a minor population at the site of inflammation, autoantigen-specific T cells are selectively recruited and/or retained in the arthritic joint and may be playing a significant role in the pathogenesis of the autoimmune arthritis. In addition, this model may be very useful for studying the function in situ and the mechanism by which autoimmune T cells are recruited to the site of inflammation.
21182780 Mapping of citrullinated fibrinogen B-cell epitopes in rheumatoid arthritis by imaging sur 2010 INTRODUCTION: Rheumatoid arthritis (RA) frequently involves the loss of tolerance to citrullinated antigens, which may play a role in pathogenicity. Citrullinated fibrinogen is commonly found in inflamed synovial tissue and is a frequent target of autoantibodies in RA patients. To obtain insight into the B-cell response to citrullinated fibrinogen in RA, its autoepitopes were systematically mapped using a new methodology. METHODS: Human fibrinogen was citrullinated in vitro by peptidylarginine deiminases (PAD), subjected to proteolysis and the resulting peptides were fractionated by ion exchange chromatography. The peptide composition of the citrullinated peptide-containing fractions was determined by high resolution tandem mass spectrometry. The recognition of these fractions by patient sera was subsequently analyzed by imaging surface plasmon resonance on microarrays. RESULTS: In total about two-thirds of the 81 arginines of human fibrinogen were found to be susceptible to citrullination by the human PAD2, the human PAD4 or the rabbit PAD2 enzymes. Citrullination sites were found in all three polypeptide chains of fibrinogen, although the α-chain appeared to contain most of them. The analysis of 98 anti-citrullinated protein antibody-positive RA sera using the new methodology allowed the identification of three major citrullinated epitope regions in human fibrinogen, two in the α- and one in the β-chain. CONCLUSIONS: A comprehensive overview of citrullination sites in human fibrinogen was generated. The multiplex analysis of peptide fractions derived from a post-translationally modified protein, characterized by mass spectrometry, with patient sera provides a versatile system for mapping modified amino acid-containing epitopes. The citrullinated epitopes of human fibrinogen most efficiently recognized by RA autoantibodies are confined to three regions of its polypeptides.
20391509 Denosumab prevents metacarpal shaft cortical bone loss in patients with erosive rheumatoid 2010 Apr OBJECTIVE: Osteoclast-mediated bone loss in the hand predicts future bone erosions in patients with rheumatoid arthritis (RA). Osteoclast activity depends on RANKL, which is inhibited by denosumab, an investigational fully human monoclonal antibody against RANKL. We measured metacarpal shaft cortical bone thickness using a novel computer-based technique, digital x-ray radiogrammetry (DXR), to evaluate the effects of denosumab on cortical bone in RA. METHODS: Patients (n = 227) with active, erosive RA were randomized to receive subcutaneous denosumab 60 mg or 180 mg or placebo every 6 months. All patients received stable doses of methotrexate and daily calcium and vitamin D. For this blinded post hoc analysis (n = 218), cortical bone loss was determined by DXR using computer-assisted measurement of cortical thickness and shaft width at 21 midshaft levels of the second through fourth metacarpal bones of both hands. RESULTS: At 12 months, patients receiving denosumab had significantly less metacarpal bone loss versus placebo (denosumab 60 mg: -0.0034, denosumab 180 mg: 0.0001 gain, placebo: -0.0108; P < or = 0.01 for both denosumab doses). Twelve-month decreases from baseline greater than the smallest detectable change occurred in 2 patients in the denosumab 180 mg group, 9 patients in the denosumab 60 mg group, and 12 patients in the placebo group. Negative correlation was significant between static cortical thickness ratios and static erosion scores (6 and 12 months), and for placebo, between changes in erosion scores and changes in cortical thickness ratio. CONCLUSION: Twice-yearly injections of denosumab with ongoing methotrexate treatment significantly reduced cortical bone loss in RA patients for up to 12 months. These results add to the growing evidence supporting the clinical utility of DXR.
19447772 Serum amyloid A protein stimulates CCL20 production in rheumatoid synoviocytes. 2009 Jul OBJECTIVE: Although serum amyloid A (SAA) has been used as a marker of inflammation, its role in leucocyte recruitment and angiogenesis has not been well established in RA. CCL20 is a chemokine involved in the migration of CCR6-expressing Th17 cells. To study the contribution of SAA to the recruitment of Th17 cells, we investigated the effects of SAA on CCL20 production by RA synoviotytes. METHODS: Synoviocytes isolated from RA patients were stimulated with recombinant SAA and cellular supernatants were analysed by CCL20-specific ELISA. CCL-20 mRNA expression was analysed by RT-PCR. RESULTS: SAA is a most potent inducer of CCL20 secretion in RA synoviocytes compared with other inflammatory cytokines (IL-1beta, TNF-alpha and IL-17A). SAA stimulation induced CCL20 mRNA expression in RA synoviocytes, which was not affected by polymyxin B pre-treatment. SAA-induced CCL20 production was down-regulated by NF-kappaB inhibition and partially by c-jun N-terminal kinase (JNK) inhibition. SAA-induced CCL20 production was also suppressed by dexamethasone or FK506. CONCLUSION: These findings suggest that SAA may be implicated in the recruitment of lymphocytes, including CCR6-expressing Th17 cells, in RA synovium by up-regulating CCL20 production in synoviocytes.
20217172 New low-field extremity MRI, compacTscan: comparison with whole-body 1.5 T conventional MR 2010 Aug Low-field extremity magnetic resonance imaging (lfMRI) is currently commercially available and has been used clinically to evaluate rheumatoid arthritis (RA). However, one disadvantage of this new modality is that the field of view (FOV) is too small to assess hand and wrist joints simultaneously. Thus, we have developed a new lfMRI system, compacTscan, with a FOV that is large enough to simultaneously assess the entire wrist to proximal interphalangeal joint area. In this work, we examined its clinical value compared to conventional 1.5 tesla (T) MRI. The comparison involved evaluating three RA patients by both 0.3 T compacTscan and 1.5 T MRI on the same day. Bone erosion, bone edema, and synovitis were estimated by our new compact MRI scoring system (cMRIS) and the kappa coefficient was calculated on a joint-by-joint basis. We evaluated a total of 69 regions. Bone erosion was detected in 49 regions by compacTscan and in 48 regions by 1.5 T MRI, while the total erosion score was 77 for compacTscan and 76.5 for 1.5 T MRI. These findings point to excellent agreement between the two techniques (kappa = 0.833). Bone edema was detected in 14 regions by compacTscan and in 19 by 1.5 T MRI, and the total edema score was 36.25 by compacTscan and 47.5 by 1.5 T MRI. Pseudo-negative findings were noted in 5 regions. However, there was still good agreement between the techniques (kappa = 0.640). Total number of evaluated joints was 33. Synovitis was detected in 13 joints by compacTscan and 14 joints by 1.5 T MRI, while the total synovitis score was 30 by compacTscan and 32 by 1.5 T MRI. Thus, although 1 pseudo-positive and 2 pseudo-negative findings resulted from the joint evaluations, there was again excellent agreement between the techniques (kappa = 0.827). Overall, the data obtained by our compacTscan system showed high agreement with those obtained by conventional 1.5 T MRI with regard to diagnosis and the scoring of bone erosion, edema, and synovitis. We conclude that compacTscan is useful for diagnosis and estimation of disease activity in patients with RA.
20827191 Modified phospholipids as anti-inflammatory compounds. 2010 Dec PURPOSE OF REVIEW: Oxidized phospholipids (OxPLs) are abundantly found at sites of inflammation and are considered to play an active role in the modulation of the immune response. Whereas most studies attributed a proinflammatory role to OxPLs, recent studies demonstrate that some products of phospholipid oxidation may in fact exhibit anti-inflammatory properties. This study summarizes the proinflammatory and anti-inflammatory properties of OxPLs and sheds light on the therapeutic potential of OxPL derivatives or analogs for treatment of chronic inflammatory disorders. RECENT FINDINGS: OxPLs may inhibit activation of several Toll-like receptors and can epigenetically reduce the capacity of dendritic cells to function as mature, fully functional immunostimulatory cells. These data demonstrate that OxPLs can induce anti-inflammatory effects. Moreover, VB-201, an orally available synthetic phospholipid analog of the Lecinoxoid family, was found to attenuate inflammation in various preclinical animal models and is currently employed in a phase II clinical trial in psoriasis. SUMMARY: Chemical or biological modifications of phospholipids yield various products, some of which may exhibit anti-inflammatory properties. Identification of such species and generation of more stable/potent anti-inflammatory OxPL variants may represent a novel approach for the treatment of immune-mediated diseases such as psoriasis, atherosclerosis, multiple sclerosis and rheumatoid arthritis.
19359735 [Phytochemical investigation of Juniper rufescens leaves and fruits]. 2009 Mar Seven species of juniper grow in Azerbaijan. The examination of leaves and fruits of Juniperus oxycedrus L. growing in Azerbaijan was conducted. It was found that Juniperus oxycedrus L is widespread in Azerbaijan. The biologically active substances of Juniperus oxycedrus leaves have been studied. It was found that the main biologically active substances in leaves are flavonoids -1,61% and lipids -57,8%; in fruits - ethereal oil 1,2%. The flavonoid composites include luteolin, kaempferol, quercetine, izoquercitrin, rutin. They also possess the diuretic and anti-inflammation effects. Ethereal oil of fruits consist of 20 components, prevailing are alpha-beta-pinen, alpha-fellandren, alpha-terpineol and it also possesses high antimicrobial and antibacterial effect. Lipoid fraction includes tokoferols, karotinoids, xlorofils and lipoid acids: linol, linolen, olein, stearin and palmithin. There are also macroelements K,Ca, Mg,Na,and mikroelements Si, Fe, Al. It was found that the period of maximum accumulation of flavonoids in leaves and ethereal oil in fruit is in Autumn in the period of fruit maturation and ripening. Juniperus oxycedrus L is a good material for new antiseptic remedy. Flavonoids from the leaves of Juniperus oxycedrus L have anti-inflammatory and diuretic effect; fungicide, antimicrobial and antibacterial characteristics.
21055346 [Inhibitory effect of total glucosides of paeonia on the NF-κB/p65 protein expression in 2010 Nov AIM: To explore effects of total glucosides of paeonia (TGP)on the NF-κB/p65 protein expression in paws of rheumatoid arthritis (RA) rats, and the contents of serum TNF-α, IL-1β and IL-10 in RA rats serum. METHODS: Type II collagen-induced arthritis model in SD rats was established. The expression of NF-κB/p65 proteins in rat, s paw tissues was detected by immunohistochemical staining. The contents of serum TNF-α, IL-1β and IL-10 in RA rats were detected by ELISA. RESULTS: TGP could down-regulate the expression of NF-κB/ p65 protein and contents of TNF-α, IL-1β and IL-10 in RA rats. CONCLUSION: The inhibitory effect of TGP on anti-inflammation maybe related to decreasing the expression of NF-κB/p65 protein and suppressing the production of TNF-α and IL-1β in RA rats.
20040530 Differential effects of anti-TNF-alpha drugs on fibroblast-like synoviocyte apoptosis. 2010 Mar OBJECTIVE: Novel drugs targeting TNF-alpha are available for treatment of RA. Fibroblast-like synoviocytes (FLSs) play a fundamental role in RA progression, through their expansion caused in part by resistance to cell death induction. The aim of our study was to determine the effects of different anti-TNF-alpha agents on FLS apoptosis. METHODS: FLS from patients with either RA or OA were co-cultured with peripheral blood mononuclear cells (PBMCs), and incubated with various drugs for 6 days. Subsequently, apoptosis induction was detected by Nucleosome ELISA and terminal deoxynucleotidyl transferase dUTP nick end labeling. Western blot was used to determine the activation of the phosphatase and tensin homologue deleted on chromosome 10 (PTEN)-focal adhesion kinase (FAK) pathway as well as Bax and Bcl-2 levels. Immunoprecipitation was used for studying phosphorylation of transmembrane TNF-alpha (tmTNF-alpha). RESULTS: All the tested drugs induced apoptosis of FLSs in the presence of PBMCs obtained from the same patient only when the two cell populations were in direct contact by activating the PTEN-FAK pathway and increasing Bax levels. This effect was not due to antibody-dependent cell-mediated cytotoxicity. Only the two antibodies infliximab and adalimumab were able to up-regulate Bcl-2. CONCLUSIONS: Etanercept is more effective in inducing FLS apoptosis compared with the other drugs tested. This induction is dependent on the presence of PBMCs, and involves the activation of PTEN-FAK pathway. Bcl-2 increase induced by the monoclonal antibodies infliximab and adalimumab may play a protective role and thus counteract their pro-apoptotic effect on FLSs.
20663637 Dermatitis associated with chromium following total knee arthroplasty. 2011 Jun All metal implants release metal ions because of corrosion. Although 20% to 25% of patients develop metal sensitivity after total joint arthroplasty, which is 10% higher than that in the general population, only very few highly susceptible patients exhibit symptoms. Even patients with known metal allergy often do not react to their metal prosthesis. Systemic allergic contact dermatitis is particularly uncommon with total knee arthroplasty because there is no metal-on-metal contact between the femoral and tibial components. We present a case report of 62-year-old man with dermatitis most likely caused by chromium after total knee arthroplasty and review the relevant literature. Although this complication is very rare, it sometimes can be painful enough for the patient to undergo revision surgery.
20214227 Determination of advanced glycation end-products on IgG in liver cirrhosis. 2009 Nov BACKGROUND/AIMS: Our previous report showed that IgG levels are strongly correlated with the indocyanine green (ICG) retention rate in patients with liver cirrhosis (LC). This correlation suggests that hyperglobulinemia in LC could be explained by impairment of hepatic removal function. To estimate IgG turnover in LC, in the present paper was determined the advanced glycation end-products (AGE) on IgG as a marker of half-life. METHODOLOGY: Serum samples were obtained from patients with LC, rheumatoid arthritis (RA), and Sjögren syndrome (SjS), and from age-matched control patients. IgG was purified from serum by the protein G-based affinity method, concentrated by filtration, and used for assay of Nepsilon-(carboxymethyl) lysine (CML), a predominant AGE, by ELISA. RESULTS: CML on IgG was significantly lower in patients with LC than in control patients, whereas there was no significant difference in total serum CML levels among patients with LC, RA, and SjS, and control patients. CML levels on IgG were negatively correlated with serum IgG levels in patients with LC, RA, and Sjögren syndrome SjS. CONCLUSIONS: Based on these findings, it is suggested that IgG turnover is not likely to be prolonged but rather may be shortened in LC It may be concluded that, hyperglobulinemia is primarily caused by enhanced synthesis followed by up-regulation of catabolism of immunoglobulins.
19758245 Localization of antimicrobial peptides human beta-defensins in minor salivary glands with 2009 Oct Sjögren's syndrome is a common systemic autoimmune disease associated with inflammatory cells that infiltrate exocrine glands. The antimicrobial peptides human beta-defensin-1, human beta-defensin-2, and human beta-defensin-3 are expressed in various human epithelial cells and in normal salivary glands. Antimicrobial peptides provide local protection against infection and participate in inflammatory responses. Because of the presence of inflammation, we hypothesized that human beta-defensin expression in minor salivary glands may be increased in subjects with Sjögren's syndrome. However, the expression of human beta-defensins 1 and 2 was decreased in salivary glands affected by Sjögren's syndrome in comparison with the human beta-defensin expression patterns in salivary glands from normal subjects. In addition, the reduction in expression of human beta-defensin-2 was greater than the reduction in expression of human beta-defensin-1. The aforementioned result suggests that the reduction in expression of human beta-defensin-2 may occur earlier than the reduction in expression of human beta-defensin-1, which may lead to a greater decrease in human beta-defensin-2 than in human beta-defensin-1 during disease progression.