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ID PMID Title PublicationDate abstract
23808883 The carbohydrate switch between pathogenic and immunosuppressive antigen-specific antibodi 2013 Aug IgG antibodies have one conserved N-glycosylation site at Asn 297 in each of their constant heavy chain regions. These Fc glycans influence the overall structure and pro- or anti-inflammatory effector functions of IgG antibodies. The biantennary core glycan structure, consisting of four N-acetyl-glucosamine (GlcNAc) and three mannose residues, can be further decorated with fucose, a bisecting GlcNAc and terminal galactose or galactose plus sialic acid. Non-galactosylated (agalactosylated; G0) IgG antibodies have long been associated with pro-inflammatory effector functions in autoimmune patients with rheumatoid arthritis (RA). In contrast, it has been shown that sialylated IgGs are responsible for anti-inflammatory effects of intravenous immunoglobulin (IVIG; purified IgG from pooled human plasma), which is administered at high doses (2 g/kg) for the systemic treatment of autoimmune patients. It has become increasingly evident that pro-inflammatory immune responses, such as autoimmune reactions, primarily induce antigen-specific G0 IgGs, whereas tolerance induces immunosuppressive galactosylated and sialylated IgGs. Under physiological conditions, differentially glycosylated IgGs mediate their pro- or anti-inflammatory effector functions obviously as immune complexes (IC) in an antigen-specific manner. Therefore, antigen-specific galactosylated and sialylated IgGs may be a promising therapeutic tool for re-establishing tolerance against defined (self-) antigens in autoimmune or allergic patients. Here, we summarize these findings and outline our viewpoint on the development and function of differentially glycosylated antigen-specific IgG antibodies.
25548435 Elevated serum IgG4 defines specific clinical phenotype of rheumatoid arthritis. 2014 OBJECTIVES: To explore the correlation of serum IgG4 (sIgG4) with clinical manifestations or therapeutic response in rheumatoid arthritis (RA). METHODS: Consecutive 136 RA patients were recruited and followed up at regular interval. SIgG4 was detected by immunonephelometry. Serial synovial tissue sections from 46 RA patients were stained immunohistochemically for IgG4. RESULTS: Forty-six percent of 136 RA patients had elevated sIgG4. Patients with elevated sIgG4 had higher sIgG4/sIgG ratio, C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, and anticyclic citrullinated peptide antibodies than those with normal sIgG4 (all P < 0.05). Among 45 patients who received methotrexate and leflunomide therapy, 50% (9/18) of patients with elevated sIgG4 and 85% (23/27) of patients with normal sIgG4 reached therapeutic target (disease activity score of 28 joints < 3.2) at 6-month visit (χ(2) = 6.508, P = 0.011). IgG4-positive plasma cell count correlated positively with sIgG4, total synovitis score, and CD3-, CD20-, and CD38-positive cell counts (all P < 0.05). CONCLUSIONS: Our results showed that elevated sIgG4 in RA is common and disproportional to total IgG and RA with elevated sIgG4 may be a specific clinical phenotype with higher disease activity, higher level of autoantibodies, and poor response to methotrexate and leflunomide therapy.
23075431 Prevalence and severity of periodontitis in Indonesian patients with rheumatoid arthritis. 2013 Aug BACKGROUND: Patients with rheumatoid arthritis (RA) may have more prevalent and severe periodontitis than healthy controls. Periodontitis may increase the systemic inflammation in RA. The aim of this study is to assess periodontitis prevalence and severity and its potential association with systemic inflammation in Indonesian patients with RA. METHODS: A full-mouth periodontal examination including probing depth, gingival recession, plaque index, and bleeding on probing was performed in 75 Indonesians with RA and 75 age-, sex-, and smoking-matched Indonesian controls. A validated questionnaire was used to assess smoking, body mass index, education, and medical conditions. In addition, in all participants, the use of drugs was noted, and erythrocyte sedimentation rates and serum levels of high-sensitivity C-reactive protein (hsCRP), rheumatoid factor, and anti-citrullinated protein antibodies were measured. Differences in periodontitis prevalence and 12 measures of periodontitis severity between patients with RA and controls were analyzed using univariate analyses. RESULTS: No significant differences in periodontitis prevalence and 11 measures of periodontitis severity between patients with RA and controls were observed. Conversely, patients with RA had a significantly lower surface area of healthy pocket epithelium versus controls (P = 0.008), and a tendency toward higher hsCRP levels was observed in patients with RA with severe periodontitis compared with patients with RA with no mild or moderate periodontitis (P = 0.063). It has to be noted that all patients with RA were on anti-inflammatory drugs, whereas none of the controls used such drugs. CONCLUSION: Prevalence and severity of periodontitis in Indonesian patients with RA is comparable to controls but with less healthy pocket epithelium than in controls and a tendency toward a higher inflammatory state in patients with RA and severe periodontitis.
25228842 Efficacy and safety of tofacitinib for active rheumatoid arthritis with an inadequate resp 2014 Sep BACKGROUND/AIMS: The aim of this study was to assess the efficacy and safety of tofacitinib (5 and 10 mg twice daily) in patients with active rheumatoid arthritis (RA). METHODS: A systematic review of randomized controlled trials (RCTs) that examined the efficacy and safety of tofacitinib in patients with active RA was performed using the Medline, Embase, and Cochrane Controlled Trials Register databases as well as manual searches. RESULTS: Five RCTs, including three phase-II and two phase-III trials involving 1,590 patients, met the inclusion criteria. The three phase-II RCTs included 452 patients with RA (144 patients randomized to 5 mg of tofacitinib twice daily, 156 patients randomized to 10 mg of tofacitinib twice daily, and 152 patients randomized to placebo) who were included in this meta-analysis. The American College of Rheumatology 20% response rate was significantly higher in the tofacitinib 5- and 10-mg groups than in the control group (relative risk [RR], 2.445; 95% confidence interval [CI], 1.229 to 4.861; p = 0.011; and RR, 2.597; 95% CI, 1.514 to 4.455; p = 0.001, respectively). The safety outcomes did not differ between the tofacitinib 5- and 10-mg groups and placebo groups with the exception of infection in the tofacitinib 10-mg group (RR, 2.133; 95% CI, 1.268 to 3.590; p = 0.004). The results of two phase-III trials (1,123 patients) confirmed the findings in the phase-II studies. CONCLUSIONS: Tofacitinib at dosages of 5 and 10 mg twice daily was found to be effective in patients with active RA that inadequately responded to methotrexate or disease-modifying antirheumatic drugs, and showed a manageable safety profile.
25417613 Hepatic granulomas in Turkey: a 6-year clinicopathological study of 35 cases. 2014 Oct BACKGROUND/AIMS: Granulomas are focal aggregates of modified macrophages that are surrounded by a rim of lymphocytes and fibroblasts. The present study aimed to evaluate the prevalence and etiology of hepatic granulomas (HGs) in the Department of Gastroenterology with a wider population. MATERIALS AND METHODS: We performed a retrospective study on 2662 liver biopsy specimens analyzed between 2005 and 2011 at Gazi University Department of Gastroenterology to determine the presence of HGs. RESULTS: There were 16 cases with primary biliary cirrhosis, of whom 14 without any other causative etiology. There were 6 cases of sarcoidosis, 2 cases of Fasciola hepatica infection, 2 cases of hepatitis C, and 2 cases of hepatitis B. One case had both tuberculosis and rheumatoid arthritis and one case had both tuberculosis and brucellosis. There was also one case each of leishmaniasis and Hodgkin's lymphoma. The diagnosis of autoimmune hepatitis was found in two cases. One case had immune cholangiopathy. CONCLUSION: The leading causative etiology of HGs was primary biliary cirrhosis, followed by sarcoidosis. As a study performed in a center that accepts patient profiles throughout Turkey, tuberculosis took a minor part in HG etiology. A drug-affected or toxic case of HG was not observed.
23818173 Death receptor 5-targeted depletion of interleukin-23-producing macrophages, Th17, and Th1 2013 Oct OBJECTIVE: Bidirectional interactions between granulocyte-macrophage colony-stimulating factor-positive (GM-CSF+) T cells and interferon regulatory factor 5-positive (IRF-5+) macrophages play a major role in autoimmunity. In the absence of SH2 domain-containing phosphatase 1 (SHP-1), GM-CSF-stimulated cells are resistant to death receptor (DR)-mediated apoptosis. The objective of this study was to determine whether TRA-8, an anti-DR5 agonistic antibody, can eliminate inflammatory macrophages and CD4 T cells in the SHP-1-deficient condition. METHODS: Ubiquitous Cre (Ubc.Cre) human/mouse-chimeric DR5-transgenic mice were crossed with viable SHP-1-defective motheaten (mev/mev) mice. TRA-8 was administered weekly for up to 4 weeks. The clinical scores, histopathologic severity, and macrophage and CD4 T cell phenotypes were evaluated. The role of TRA-8 in depleting inflammatory macrophages and CD4 T cells was also evaluated, using synovial fluid obtained from patients with rheumatoid arthritis (RA). RESULTS: The levels of inflammatory macrophages (interleukin-23-positive [IL-23+] IRF-5+) and CD4 T cells (IL-17+ GM-CSF+) were elevated in mev/mev mice. In DR5-transgenic mev/mev mice, DR5 expression was up-regulated in these 2 cell populations. TRA-8 treatment depleted these cell populations and resulted in a significant reduction in inflammation and in the titers of autoantibodies. In synovial cells from patients with RA, the expression of IRF5 and DR5 was negatively correlated with the expression of PTPN6. TRA-8, but not TRAIL, suppressed RA inflammatory macrophages and Th17 cells under conditions in which the expression of SHP-1 is low. CONCLUSION: In contrast to TRAIL, which lacks the capability to counteract the survival signal in the absence of SHP-1, TRA-8 eliminated both IRF-5+ IL-23+ M1 macrophages and pathogenic GM-CSF+ IL-17+ CD4 T cells in a SHP-1-independent manner. The results of the current study suggest that TRA-8 can deplete inflammatory cell populations that result from a hyperactive GM-CSF/IRF-5 axis.
23280063 Interaction with activated monocytes enhances cytokine expression and suppressive activity 2013 Mar OBJECTIVE: Despite the high frequency of CD4+ T cells with a regulatory phenotype (CD25+CD127(low) FoxP3+) in the joints of patients with rheumatoid arthritis (RA), inflammation persists. One possible explanation is that human Treg cells are converted into proinflammatory interleukin-17 (IL-17)-producing cells by inflammatory mediators and thereby lose their suppressive function. The aim of this study was to investigate whether activated monocytes, which are potent producers of inflammatory cytokines and are abundantly present in the rheumatic joint, induce proinflammatory cytokine expression in human Treg cells and impair their regulatory function. METHODS: The presence and phenotype of CD4+CD45RO+CD25+CD127(low) T cells (memory Treg cells) and CD14+ monocytes in the peripheral blood (PB) and synovial fluid (SF) of patients with RA were investigated by flow cytometry. Memory Treg cells obtained from healthy control subjects underwent fluorescence-activated cell sorting and then were cocultured with autologous activated monocytes and stimulated with anti-CD3 monoclonal antibodies. Intracellular cytokine expression, phenotype, and function of cells were determined by flow cytometry, enzyme-linked immunosorbent assay, and proliferation assays. RESULTS: In patients with RA, the frequencies of CD4+CD45RO+CD25+CD127(low) Treg cells and activated CD14+ monocytes were higher in SF compared with PB. In vitro-activated monocytes induced an increase in the percentage of IL-17-positive, interferon-γ (IFNγ)-positive, and tumor necrosis factor α (TNFα)-positive Treg cells as well as IL-10-positive Treg cells. The observed increase in IL-17-positive and IFNγ-positive Treg cells was driven by monocyte-derived IL-1β, IL-6, and TNFα and was mediated by both CD14+CD16- and CD14+CD16+ monocyte subsets. Despite enhanced cytokine expression, cells maintained their CD25+FoxP3+CD39+ Treg cell phenotype and showed an enhanced capacity to suppress T cell proliferation and IL-17 production. CONCLUSION: Treg cells exposed to a proinflammatory environment show increased cytokine expression as well as enhanced suppressive activity.
23138447 Evaluation of the efficacy and safety of etanercept 50 mg once weekly in Japanese patient 2013 Sep OBJECTIVE: Tumor necrosis factor-α inhibitors have been available in recent years for treating early and established rheumatoid arthritis (RA). Twice-weekly administration of 25 mg etanercept (ETN) has demonstrated efficacy and safety. The objective of this study was to evaluate the efficacy of once-weekly administration of 50 mg ETN (ETN50), and to compare it with that of twice-weekly administration of 25 mg ETN (ETN25). METHODS: The ETN50 group comprised 29 patients and the ETN25 group 26. The analysis compared changes from baseline in Disease Activity Score in 28 joints (DAS28)-C reactive protein (CRP) and DAS28-erythrocyte sedimentation rate (ESR) between the ETN50 and ETN25 groups. RESULTS: Overall, 42.3 % of ETN50 patients achieved DAS28-ESR remission (<2.6), and 76.9 % experienced low disease activity at 24 weeks. Patients in the ETN50 group also experienced more significant improvement in DAS28-ESR at 4 weeks, higher DAS28-ESR remission rates, and lower disease activity rates than ETN25 group patients. No serious adverse events were experienced in the safety analysis set (ETN50 group). CONCLUSION: These results suggest that ETN50 can lead to earlier remission and higher remission rates compared with ETN25 in patients with RA.
24287823 Effect of IL-15 and natural killer cells on osteoclasts and osteoblasts in a mouse cocultu 2014 Jun This study analyzes the effect of interleukin-15 (IL-15) on osteoclast formation using a coculture of mouse osteoblasts and bone marrow cells (BMCs) stimulated with prostaglandin E2 (PGE2), which both have important role in rheumatoid arthritis (RA) and periodontal disease (PD). BMCs isolate lacking T (BM(T-)) or NK (BM(NK-)) cells, BMCs with no cells removed (BM(T+NK+)), purified NK cells, and purified T cells were each cocultured with osteoblasts in the presence or absence of PGE2 and/or IL-15. The number of both osteoclasts and osteoblasts was decreased by IL-15 in a dose-dependent manner in BM(T+NK+), BM(T-). However, the reductions were improved in BM(NK-). The expression of caspase3 in osteoblasts cocultured with NK cells was increased in a dose-dependent manner by IL-15. IL-15 stimulates apoptosis of osteoblasts via activation of NK cells. Since osteoblasts have an important role in bone formation, IL-15 may be an inflammatory bone destructive factor in RA and PD.
24919467 Dipeptidyl peptidase-4 inhibitors in type 2 diabetes may reduce the risk of autoimmune dis 2015 Nov OBJECTIVE: Dipeptidyl peptidase-4 (DPP4), also known as CD26, is a transmembrane glycoprotein that has a costimulatory function in the immune response. DPP4 inhibitors (DPP4i) are oral glucose-lowering drugs for type 2 diabetes mellitus (T2DM). This study evaluated the risk of incident rheumatoid arthritis (RA) and other autoimmune diseases (AD) such as systemic lupus erythematosus, psoriasis, multiple sclerosis and inflammatory bowel disease, associated with DPP4i in patients with T2DM. METHODS: Using US insurance claims data (2005-2012), we conducted a population-based cohort study that included initiators of combination therapy with DPP4i (DPP4i plus metformin) and non-DPP4i (non-DPP4i plus metformin). RA and other AD were identified with ≥2 diagnoses and ≥1 dispensing for AD-specific immunomodulating drugs or steroids. Composite AD includes RA or other AD. Propensity score (PS)-stratified Cox proportional hazards models compared the risk of AD in DPP4i initiators versus non-DPP4i, controlling for potential confounders. RESULTS: After asymmetric trimming on the PS, 73 928 patients with T2DM starting DPP4i combination therapy and 163 062 starting non-DPP4i combination therapy were selected. Risks of incident RA and composite AD were lower in the DPP4i group versus non-DPP4i with the PS-stratified HR of 0.66 (95% CI 0.44 to 0.99) for RA, 0.73 (0.51 to 1.03) for other AD and 0.68 (95% CI 0.52 to 0.89) for composite AD. CONCLUSIONS: In this large cohort of diabetic patients, those initiating DPP4i combination therapy appear to have a decreased risk of incident AD including RA compared with those initiating non-DPP4i combination therapy. These results may suggest possible pharmacological pathways for prevention or treatment of AD.
24599679 Late-onset neutropenia following rituximab treatment for rheumatologic conditions. 2014 Sep Rituximab is a monoclonal antibody directed against the CD20 antigen on the surface of normal and malignant B lymphocytes. Its use in autoimmune conditions is rapidly expanding. Late-onset neutropenia (LON) is a well-recognized side effect of rituximab therapy in lymphoma patients. Only a small number of cases of LON have been reported in patients with autoimmune disorders. The aim of this work is to review cases in Israel and to compare them to published cases in the literature thus adding to the body of knowledge regarding this unusual phenomenon. Members of the Israeli Rheumatology Association were encountered by e-mail, requesting reports of cases of LON after therapy with rituximab. Submitted cases were reviewed, with demographics and clinical data collated and tabled. Current cases were compared to previously published rheumatology cases. Twelve episodes of LON following rituximab therapy were reported. All patients were female with an average age of 50 years (range 22-78). LON occurred at an average of 155 days after therapy (range 71-330). The average leukocyte count was 1,456 white cells, with an average of 413 neutrophils (range 0-1,170 neutrophils). Three of the patients underwent bone marrow biopsies which showed white cell line maturation arrest with an increased number of lymphocytes. No blasts were seen. Our results add support to the growing evidence that this adverse event usually follows a benign course and is not an absolute contraindication for repeat treatment if required in the future. However, vigilance is recommended with routine periodic blood counts, especially 5 months following rituximab administration when the risk is expected to be the highest.
25125593 Tumour necrosis factor inhibitor therapy and infection risk in axial spondyloarthritis: re 2015 Jan OBJECTIVES: Long-term data on infection risk in axial SpA (axSpA) are sparse. TNF inhibitors (TNFis) are increasingly being used in axSpA, with infection being the most important adverse event. We aimed to investigate the frequency of infections in axSpA and to identify factors predisposing to infection. METHODS: Data were extracted from a longitudinal observational cohort of patients with axSpA. Infection rates were calculated and multivariate analysis was performed to investigate the association of independent variables with infection. RESULTS: Data were analysed for 440 patients followed for a total of 1712 patient-years (pys). A total of 259 infections, of which 23 were serious, were recorded in 185 patients. The overall rate of any infection was 15 (95% CI 13, 17)/100 pys and the serious infection rate was 1.3 (95% CI 0.9, 2.0)/100 pys. There was no significant difference in the rate of any infection or serious infection in patients on TNFis compared with patients never on biologic agents. In the multivariate analysis, DMARD treatment, but not TNFi treatment, was associated with risk of infection. Age, disease duration, smoking status, BASFI, BASDAI, co-morbidity score and hospitalization were not associated with an increased risk of infection. CONCLUSION: The serious infection rate in axSpA in this observational cohort is low when compared with rates reported in other rheumatic diseases. Biologic use was not a significant risk factor for serious infection.
24452947 Increased apoptosis induction in CD4+ CD25+ Foxp3+ T cells contributes to enhanced disease 2014 BACKGROUND: Abnormality in the number and function of regulatory T cells (Tregs) has been linked to initiation and progression in patients with Rheumatoid Arthritis (RA). AIM: This study aims to demonstrate the apoptosis status of regulatory T cells (Tregs) and its correlation with clinical activity of RA patients and the effect of interleukin-10 (IL-10) on Tregs apoptosis in RA. MATERIALS AND METHODS: Apoptosis rates and its related molecules including Fas, Bcl-2, Caspase-3 and Caspase-8 were examined using flow cytometry. The correlation between the apoptosis level of Tregs and clinical activity parameters including ESR (erythrocyte sedimentation rate), CPR (C reactive protein), RF (Rheumatoid Factor) and DAS28 (Disease activity score 28) was analysed. PBMCs isolated from RA patients were cultured with IL-10 or anti-IL-10, and the apoptosis frequency of Tregs was then analyzed. RESULTS: The frequency of Tregs in active RA patients was decreased, and Fas, Caspase-3 and Caspase-8 expression on Tregs was much higher compared with the healthy subjects. The expression of anti-apoptotic protein, Bcl-2 on Tregs did not display significant changes between active RA patients and healthy subjects. There was a significantly positive correlation between the levels of apoptosis rates and Caspase-3 expression in Tregs and DAS28 of active RA patients. The apoptosis rates of Tregs in RA patients decreased or increased, respectively, following treatment with IL-10 or anti-IL-10 antibody in vitro. CONCLUSIONS: Apoptosis pathways are defective in Treg cells from RA patients with active disease. IL-10 treatment can modulate apoptosis in Tregs via extrinsic (type I) pathway, which may lead to restoration of the Tregs towards that of controlling autoimmune reaction in RA patients.
25200918 The return of subscapularis strength after shoulder arthroplasty. 2015 Feb BACKGROUND: During shoulder arthroplasty, the subscapularis tendon is released and repaired. Whether subscapularis strength subsequently returns to normal is poorly understood. This study's purpose was to determine whether subscapularis strength returns to normal after shoulder replacement and whether any preoperative factors predict the return of strength postoperatively. METHODS: Sixty-four patients underwent unilateral shoulder arthroplasty. Subscapularis strength was compared between the surgical and contralateral (normal) limbs at baseline (preoperatively) and follow-up. In addition, operative arm subscapularis strength recovery was compared with ipsilateral supraspinatus strength recovery. Independent variables were assessed for their effect on subscapularis strength, including sex, age, dominant-side surgery, preoperative strength, preoperative external rotation, subscapularis management technique, and fatty infiltration. RESULTS: The mean subscapularis strength ratio at 24 months from baseline was 1.19 ± 2.23 (P = .0007). The normal side was significantly stronger than the operative side at all time points (P < .0001). The operative-side subscapularis mean strength ratio was 0.54 ± 0.28 of normal at baseline and 0.70 ± 0.24 at 24 months. Defining normal strength as ±15%, 15% of patients were normal at baseline up to 22% at 24 months. At 24 months, the mean supraspinatus strength ratio from baseline (3.13 ± 6.11) was significantly greater than the subscapularis mean strength ratio (P = .0007). Multivariable regression analysis did not demonstrate any correlation (P > .05) between the independent variables studied and final subscapularis strength. DISCUSSION: Although significant strength improvement from baseline was observed at 2 years after shoulder arthroplasty, subscapularis strength returned to normal in only a minority of patients. Potential prognostic variables associated with final subscapularis strength remain elusive.
23462628 A report from the American college of rheumatology/association of rheumatology health prof 2013 Feb The annual meeting of the American College of Rheumatology (ACR), jointly held with the Association of Rheumatology Health Professionals (ARHP), brought together attendees focused on all aspects of rheumatology, including researchers looking into treatment options and various services around the care of rheumatologic conditions. As well as networking opportunities at the meeting, there were a wide range of symposia and posters available covering various conditions and levels of research. There were also educational and meet-the-professor sessions. This report will cover a selection of interesting talks from poster and oral sessions on the latest preclinical and clinical research.
23148091 Interaction between oxidative stress and smoking is associated with an increased risk of r 2013 Mar OBJECTIVE: To investigate the relationship between oxidative stress and smoking and development of RA. METHODS: A case-control study was conducted in treatment-naïve early-onset RA patients and healthy controls, matched by age, gender and current smoking habit. Plasma lipid hydroperoxides (LOOH), carbonyl protein (CP) and malonyldialdehyde (MDA) levels were measured to estimate oxidative stress. Smoking exposure was quantified in pack-years. The presence of an interaction between oxidative stress and smoking exposure was investigated using three measures of additive interaction: relative excess risk due to the interaction (RERI), attributable proportion due to the interaction (AP) and the synergy index (S). RESULTS: A total of 65 RA patients and 65 healthy controls were included. Statistically significant differences were observed in RA-related variables, age, BMI and smoking dose between cases and controls. Plasma LOOH and CP levels were associated with RA risk, which was more prominent for LOOH levels >27.9 µM [odds ratio (OR) 18.8] and CP levels >64.3 µM (OR 24.9). A reverse association was observed between MDA levels and RA risk, OR 6.4 for MDA levels <8.5 µM. Having >20 pack-years increased risk for RA with an OR of 19.7. The interaction between smoking and oxidative stress increased RA risk significantly, and RERI between LOOH, CP or MDA and smoke exposure were 8.2, 5.0 and 51.5, respectively. CONCLUSION: These data suggest that the interaction between oxidative stress and smoking increases RA risk.
25469092 Percutaneous vertebroplasty of the entire thoracic and lumbar vertebrae for vertebral comp 2014 Nov Glucocorticosteroid-induced osteoporosis is the most frequent of all secondary types of osteoporosis, and can increase the risk of vertebral compression fractures (VCFs). There are promising additions to current medical treatment for appropriately selected osteoporotic patients. Few studies have reported on the efficiency of percutaneous vertebroplasty (PVP) or kyphoplasty for whole thoracic and lumbar glucocorticosteroid-induced osteoporotic vertebral compression fractures. We report a case of a 67-year-old man with intractable pain caused by successional VCFs treated by PVP.
23533458 Roles of γδ T cells in the pathogenesis of autoimmune diseases. 2013 γδ T cells are a minor population of T cells that express the TCR γδ chains, mainly distributed in the mucosal and epithelial tissue and accounting for less than 5% of the total T cells in the peripheral blood. By bridging innate and adaptive immunity, γδ T cells play important roles in the anti-infection, antitumor, and autoimmune responses. Previous research on γδ T cells was primarily concentrated on infectious diseases and tumors, whereas their functions in autoimmune diseases attracted much attention. In this paper, we summarized the various functions of γδ T cells in two prototypical autoimmune connective tissue diseases, that is, SLE and RA, elaborating on their antigen-presenting capacity, secretion of proinflammatory cytokines, immunomodulatory effects, and auxiliary function for B cells, which contribute to overproduction of proinflammatory cytokines and pathogenic autoantibodies, ultimately leading to the onset of these autoimmune diseases. Elucidation of the roles of γδ T cells in autoimmune diseases is not only conducive to in-depth understanding of the pathogenesis of these diseases, but also beneficial in providing theoretical support for the development of γδ T-cell-targeted therapy.
25130613 Carbamylation of immunoglobulin abrogates activation of the classical complement pathway. 2014 Nov Post-translational modifications of proteins significantly affect their structure and function. The carbamylation of positively charged lysine residues to form neutral homoitrulline occurs primarily under inflammatory conditions through myeloperoxidase-dependent cyanate (CNO-) formation. We analyzed the pattern of human IgG1 carbamylation under inflammatory conditions and the effects that this modification has on the ability of antibodies to trigger complement activation via the classical pathway. We found that the lysine residues of IgG1 are rapidly modified after brief exposure to CNO- . Interestingly, modifications were not random, but instead limited to only few lysines within the hinge area and the N-terminal fragment of the CH2 domain. A complement activation assay combined with mass spectrometry analysis revealed a highly significant inverse correlation between carbamylation of several key lysine residues within the hinge region and N-terminus of the CH2 domain and the proper binding of C1q to human IgG1 followed by subsequent complement activation. This severely hindered complement-dependent cytotoxicity of therapeutic IgG1 . The reaction can apparently occur in vivo, as we found carbamylated antibodies in synovial fluid from rheumatoid arthritis patients. Taken together, our data suggest that carbamylation has a profound impact on the complement-activating ability of IgG1 and reveals a pivotal role for previously uncharacterized lysine residues in this process.
23108887 Tocilizumab in the treatment of the adult-onset Still's disease: current clinical evidence 2013 Jan This study aimed to review and analyze the effectiveness and safety of tocilizumab in the treatment of patients with adult-onset Still's disease (AOSD). We report on two patients with AOSD who were successfully treated with tocilizumab. All published information on the use of tocilizumab in this disease was also retrieved through a systematic review of the English-language literature. Including our cases, 35 patients were given tocilizumab for AOSD (8 mg/kg/month in 22 patients). The main clinical manifestations were arthritis in all 35 patients and systemic symptoms such as fever or skin rash in 28 (80 %). Thirty-three (94 %) patients had unsuccessfully tried other immunosuppressive agents such as methotrexate, tumor necrosis factor-α blockers, or anakinra. Most of the patients achieved a response with tocilizumab, such as a prompt articular improvement in 30/35 (86 %) patients and a disappearance of systemic symptoms in 27/28 (96 %). Twenty-eight (80 %) patients tapered their steroid intakes, including seven (20 %) who were able to discontinue them. Four (11 %) patients relapsed, and two were successfully retreated with tocilizumab. Regarding safety, tocilizumab is a well-tolerated treatment, but severe side effects such as macrophage activation syndrome or cytomegalovirus reactivation are possible and require ongoing vigilance. Our findings suggest that tocilizumab should probably be proposed in refractory AOSD, as it allows for remission to be induced and the dose of steroid intakes to be reduced. It is a well-tolerated treatment that can be administered according to the therapeutic sequence of rheumatoid arthritis. Further prospective studies are required to assess the better use of this treatment (dosage and duration) and its place among other conventional treatments.