Tumour necrosis factor allele variants and their association with the occurrence and severity of malaria in African children: a longitudinal study
Gichohi-Wainaina, W.N. ; Boonstra, A. ; Feskens, E.J.M. ; Demir, A.Y. ; Veenemans, J. ; Verhoef, H. - \ 2015
Malaria Journal 14 (2015). - ISSN 1475-2875 - 11 p.
plasmodium-falciparum malaria - tnf-alpha promoter - cerebral malaria - linkage disequilibrium - rheumatoid-arthritis - diabetes-mellitus - polymorphisms - gene - disease - hla
Background Tumour necrosis factor (TNF) is central to the immune response to Plasmodium infection. Its plasma concentration is influenced by allele variants in the promoter region of TNF. The study’s objectives were to assess TNF allele variants (TNF-1031 , TNF-308 ): (1) modulation of malaria rates in young Tanzanian children; (2) modulation of the severity of malaria as indicated by haemoglobin concentrations at the time of presentation with febrile episodes; and (3) the association between Plasmodium infection and haemoglobin concentration in symptomless parasite carriers. Methods Data from a placebo-controlled trial in which 612 Tanzanian children aged 6–60 months with height-for-age z-score in the range -3 SD to 1.5 SD was utilised. Those with Plasmodium infection at baseline were treated with artemether-lumefantrine. An episode of malaria was predefined as current Plasmodium infection with an inflammatory response (axillary temperature =37.5°C or whole blood C-reactive protein concentration =8 mg/L) in children reported sick. Linkage disequilibrium (LD) pattern assessment as well as haplotype analysis was conducted using HAPLOVIEW. Cox regression models used in the primary analysis accounted for multiple episodes per child. Results Genotyping of 94.9% (581/612) children for TNF-1031 (TNF-1031 T>C); allele frequency was 0.39. Corresponding values for rs1800629 (TNF-308 G>A) were 95.4% (584/612) and 0.17. Compared to the wild type genotype (TT), malaria rates were increased in the TNF-1031 CC genotype (hazard ratio, HR [95% CI]: 1.41 [1.01¿1.97] and 1.31 [0.97¿1.76] for crude analysis and adjusting for pre-specified baseline factors, respectively) but decreased in those with the TNF-308 AA genotype (corresponding HR: 0.13 [0.02¿0.63] and 0.16 [0.04¿0.67]). These associations were weaker when analysing first episodes of malaria (P value -0.59 and 0.38, respectively). No evidence that allele variants of TNF-1031 and TNF-308 affected haemoglobin concentration at first episode of malaria, or that they modified the association between Plasmodium infection and haemoglobin concentrations at baseline was observed.
Characterization and expression analysis of an interferon-y2 induced chemokine receptor CXCR3 in common carp (Cyprinus carpio L.)
Chadzinska, M.K. ; Golbach, L.A. ; Pijanowski, L. ; Scheer, M.H. ; Verburg-van Kemenade, B.M.L. - \ 2014
Developmental and Comparative Immunology 47 (2014)1. - ISSN 0145-305X - p. 68 - 76.
central-nervous-system - rheumatoid-arthritis - t-cells - monoclonal-antibodies - molecular evolution - endothelial-cells - phagocytic-cells - teleost fish - b-cells - inflammation
Chemokine and chemokine receptor signalling pairs play a crucial role in regulation of cell migration, morphogenesis, and cell activation. Expressed in mammals on activated T and NK cells, chemokine receptor CXCR3 binds interferon-¿ inducible chemokines CXCL9–11 and CCL21. Here we sequenced the carp CXCR3 chemokine receptor and showed its relationship to CXCR3a receptors found in other teleosts. We found high expression of the CXCR3 gene in most of the organs and tissues of the immune system and in immune-related tissues such as gills and gut, corroborating a predominantly immune-related function. The very high expression in gill and gut moreover indicates a role for CXCR3 in cell recruitment during infection. High in vivo expression of CXCR3 at later stages of inflammation, as well as its in vitro sensitivity to IFN-¿2 stimulation indicate that in carp, CXCR3 is involved in macrophage-mediated responses. Moreover, as expression of the CXCR3 and CXCb genes coincides in the focus of inflammation and as both the CXCb chemokines and the CXCR3 receptor are significantly up-regulated upon IFN-¿ stimulation it is hypothesized that CXCb chemokines may be putative ligands for CXCR3.
Impact of diets with a high content of greaves-meal protein or carbohydrates on faecal characteristics, volatile fatty acids and faecal calprotectin concentrations in healthy dogs
Hang, I. ; Heilmann, R.M. ; Grützner, N. ; Suchodolski, J.S. ; Steiner, J.M. ; Atroshi, F. ; Sankari, S. ; Kettunen, A. ; Vos, W.M. de; Zentek, J. ; Spillmann, T. - \ 2013
BMC Veterinary Research 9 (2013). - ISSN 1746-6148 - 8 p.
calcium-binding proteins - nutrient digestibility - intestinal inflammation - bacterial metabolites - rheumatoid-arthritis - canine calprotectin - responsive diarrhea - epithelial-cells - cystic-fibrosis - body-size
BACKGROUND: Research suggests that dietary composition influences gastrointestinal function and bacteria-derived metabolic products in the dog colon. We previously reported that dietary composition impacts upon the faecal microbiota of healthy dogs. This study aims at evaluating the dietary influences on bacteria-derived metabolic products associated with the changes in faecal microbiota that we had previously reported. We fed high-carbohydrate starch based (HCS), [crude protein: 194 g/kg, starch: 438 g/kg], high-protein greaves-meal (HPGM), [crude protein: 609 g/kg, starch: 54 g/kg] and dry commercial (DC), [crude protein: 264 g/kg, starch: 277 g/kg] diets, and studied their effects on the metabolism of the colonic microbiota and faecal calprotectin concentrations in five Beagle dogs, allocated according to the Graeco-Latin square design. Each dietary period lasted for three weeks and was crossed-over with washout periods. Food intake, body weight, and faecal consistency scores, dry matter, pH, ammonia, volatile fatty acids (VFAs), and faecal canine calprotectin concentrations were determined. RESULTS: Faecal ammonia concentrations decreased with the HCS diet. All dogs fed the HPGM diet developed diarrhoea, which led to differences in faecal consistency scores between the diets. Faecal pH was higher with the HPGM diet. Moreover, decreases in propionic and acetic acids coupled with increases in branched-chain fatty acids and valeric acid caused changes in faecal total VFAs in dogs on the HPGM diet. Faecal canine calprotectin concentration was higher with the HPGM diet and correlated positively with valeric acid concentration. CONCLUSIONS: The HPGM diet led to diarrhoea in all dogs, and there were differences in faecal VFA profiles and faecal canine calprotectin concentrations
A discrete event modelling framework for simulation of long-term outcomes of sequential treatment strategies for ankylosing spondylitis
Tran-Duy, A. ; Boonen, A. ; Laar, M.A.F.J. ; Franke, A.C. ; Severens, J.L. - \ 2011
Annals of the Rheumatic Diseases 70 (2011)12. - ISSN 0003-4967 - p. 2111 - 2118.
tumor-necrosis-factor - nonsteroidal antiinflammatory drug - asas consensus statement - placebo-controlled trial - metrology index basmi - cost-effectiveness - rheumatoid-arthritis - infliximab remicade(r) - united-kingdom - clinical-trial
Objective To develop a modelling framework which can simulate long-term quality of life, societal costs and cost-effectiveness as affected by sequential drug treatment strategies for ankylosing spondylitis (AS). Methods Discrete event simulation paradigm was selected for model development. Drug efficacy was modelled as changes in disease activity (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) and functional status (Bath Ankylosing Spondylitis Functional Index (BASFI)), which were linked to costs and health utility using statistical models fitted based on an observational AS cohort. Published clinical data were used to estimate drug efficacy and time to events. Two strategies were compared: (1) five available non-steroidal anti-inflammatory drugs (strategy 1) and (2) same as strategy 1 plus two tumour necrosis factor a inhibitors (strategy 2). 13 000 patients were followed up individually until death. For probability sensitivity analysis, Monte Carlo simulations were performed with 1000 sets of parameters sampled from the appropriate probability distributions. Results The models successfully generated valid data on treatments, BASDAI, BASFI, utility, quality-adjusted life years (QALYs) and costs at time points with intervals of 1–3 months during the simulation length of 70 years. Incremental cost per QALY gained in strategy 2 compared with strategy 1 was €35 186. At a willingness-to-pay threshold of €80 000, it was 99.9% certain that strategy 2 was cost-effective. Conclusions The modelling framework provides great flexibility to implement complex algorithms representing treatment selection, disease progression and changes in costs and utilities over time of patients with AS. Results obtained from the simulation are plausible
Effects of Happiness on All-Cause Mortality During 15 Years of Follow-Up: The Arnhem Elderly Study
Koopmans, T.A. ; Geleijnse, J.M. ; Zitman, F.G. ; Giltay, E.J. - \ 2010
Journal of Happiness Studies 11 (2010)1. - ISSN 1389-4978 - p. 113 - 124.
dispositional optimism - physical-activity - cardiovascular mortality - psychosocial predictors - rheumatoid-arthritis - depressive symptoms - life orientation - risk-factors - pain - disease
Positive psychological characteristics may be beneficial for physical health. However, prospective data on the effects of happiness on survival is scarce. In a population-based cohort study, the Arnhem Elderly Study, happiness was measured by two items, being: "I have many moments of happiness" and "I often laugh happily". In Cox proportional hazard models, happiness was analyzed as a predictor of 15 year all-cause mortality for 861 (85%) of 1,012 elderly subjects aged 65-85 years. Results showed that happiness was inversely associated with mortality (age- and sex-adjusted hazard ratio of 0.78 for happy subjects versus unhappy subjects; 95% confidence interval 0.64-0.95, P = 0.01 for trend), but that this relationship was no longer statistically significant after adjustment for physical activity and prevalent morbidity. Thus, happiness predicts for lower mortality, which may partly be mediated by more physical activity and lower morbidity.
PDCD1 genes may protect against extraocular manifestations in Chinese Han patients with Vogt-Koyanagi-Harada syndrome
Meng, Q.L. ; Liu, X.L. ; Yang, P.Z. ; Hou, S.P. ; Du, L.P. ; Zhou, H.Y. ; Kijlstra, A. - \ 2009
Molecular Vision 15 (2009)40-41. - ISSN 1090-0535 - p. 386 - 392.
systemic-lupus-erythematosus - rheumatoid-arthritis - programmed cell-death-1 - regulatory polymorphism - association - disease - pd-1 - susceptibility - population - family
Purpose: To analyze the potential association of programmed cell death 1 (PDCD1) with Vogt-Koyanagi-Harada (VKH) syndrome in a Chinese Han population. Methods: Three single nucleotide polymorphism (SNPs), PD-1.3G/A, PD-1.5C/T, and PD-1.6G/A, were genotyped in 247 VKH patients and 289 age-, sex-, and ethnically-matched healthy controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The associations of genotypes and alleles with VKH syndrome were analyzed. Results: All genotype distributions in healthy controls were in Hardy-Weinberg equilibrium. The genotype and allele frequencies of PD-1.3, PD-1.5, and PD-1.6 were not different between patients with VKH syndrome and healthy controls. No significant difference was observed according to the status of human leukocyte antigen (HLA)-DR4 and HLA-DRw53. Compared to the controls, lower frequencies of the PD-1.5C genotype and allele frequencies were observed in VKH patients with extraocular findings. Conclusions: PD-1.3 and PD-1.6 polymorphisms are not associated with the susceptibility to VKH syndrome in the Chinese Han population. However, PD-1.5 may be negatively associated with the occurrence of extraocular manifestations of VKH syndrome.
Inhibitory effect of Cyclosporin A and corticosteroids on the production of IFN-gamma and IL-17 by T cells in Vogt-Koyanagi-Harada syndrome
Liu, X.L. ; Yang, P.Z. ; Lin, X.M. ; Ren, X.R. ; Zhou, H.Y. ; Huang, X.K. ; Chi, W. ; Kijlstra, A. ; Chen, L. - \ 2009
Clinical Immunology 131 (2009)2. - ISSN 1521-6616 - p. 333 - 342.
interleukin-17 production - rheumatoid-arthritis - dendritic cells - helper-cells - disease - uveitis - therapy - differentiation - inflammation - expression
Cyclosporin A (CsA) and corticosteroids are extensively used in the treatment of autoimmune diseases including Vogt-Koyanagi-Harada (VKH) syndrome. The exact immunosuppressive mechanisms of these drugs are not exactly known. Th1 and Th17 cells are important populations involved in autoimmune diseases. In this study, we investigated whether they are involved in VKH syndrome and how their function is affected by CsA and corticosteroids. The results showed that IL-17, IFN-gamma, RORgammat and T-bet were upregulated in patients with active uveitis. CsA and corticosteroids were able to downregutate all these elevated levels which correlated with the clinical improvement of the uveitis. In vitro experiments showed that CsA and dexamethasone could decrease the frequencies of Th1 and Th17 cells and inhibit IL-17 and IFN-gamma production. These data suggest that an upregulated Th1 and Th17 response is associated with active VKH syndrome. CsA and corticosteroids may exert their immunosuppressive role by downregulating Th1 and Th17 cells.
Locomotion and muscle mass measures in a murine model of collagen-induced arthritis
Hartog, A. ; Hulsman, J. ; Garssen, J. - \ 2009
BMC Musculoskeletal Disorders 10 (2009). - ISSN 1471-2474 - 7 p.
rheumatoid-arthritis - cachexia - methotrexate - inflammation - mechanisms - cytokines - pain - mice
Background: Rheumatoid arthritis (RA) is characterized by chronic poly-arthritis, synovial hyperplasia, erosive synovitis, progressive cartilage and bone destruction accompanied by a loss of body cell mass. This loss of cell mass, known as rheumatoid cachexia, predominates in the skeletal muscle and can in part be explained by a decreased physical activity. The murine collagen induced arthritis (CIA) model has been proven to be a useful model in RA research since it shares many immunological and pathological features with human RA. The present study explored the interactions between arthritis development, locomotion and muscle mass in the CIA model. Methods: CIA was induced in male DBA/1 mice. Locomotion was registered at different time points by a camera and evaluated by a computerized tracing system. Arthritis severity was detected by the traditionally used semi-quantitative clinical scores. The muscle mass of the hind-legs was detected at the end of the study by weighing. A methotrexate (MTX) intervention group was included to study the applicability of the locomotion and muscle mass for testing effectiveness of interventions in more detail. Results: There is a strong correlation between clinical arthritis and locomotion. The correlations between muscle mass and locomotion or clinical arthritis were less pronounced. MTX intervention resulted in an improvement of disease severity accompanied by an increase in locomotion and muscle mass. Conclusion: The present data demonstrate that registration of locomotion followed by a computerized evaluation of the movements is a simple non invasive quantitative method to define disease severity and evaluate effectiveness of therapeutic agents in the CIA model.f
Maldi-Tof /Tof-MS Reveals Elevated Serum Haptoglobin and Amyloid A in Behcet's Disease
Mao, L. ; Dong, H. ; Yang, P. ; Zhou, H. ; Huang, X. ; Lin, X. ; Kijlstra, A. - \ 2008
Journal of Proteome Research 7 (2008)10. - ISSN 1535-3893 - p. 4500 - 4507.
experimental autoimmune encephalomyelitis - high-abundant proteins - proteome analysis - matrix metalloproteinases - hepatocellular-carcinoma - rheumatoid-arthritis - cerebrospinal-fluid - mass-spectrometry - t-cells - biomarkers
Behcet¿s disease (BD) is a multisystemic autoimmune disease with unclear etiology and pathogenesis. To screen aberrant serum proteins in BD, serum samples were obtained from eight male BD patients with active uveitis and eight male healthy volunteers with informed consent. The serum samples from active BD patients and normal controls were pooled. Highly abundant serum proteins (albumin and IgG) were depleted from these two samples using an affinity capture based kit. The obtained samples were subjected to two-dimensional gel electrophoresis (2-DE). Protein spots were visualized with the ¿blue silver¿ staining. Differently expressed proteins were subsequently identified by matrix-assisted laser desorption /ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF-MS). Western blot and enzyme-linked immunosorbent assay (ELISA) were performed using the serum samples from 18 patients with active BD, 6 patients with inactive BD, 22 patients with Vogt-Koyanagi-Harada (VKH) syndrome, and 20 healthy volunteers to validate the results of 2-DE and MS. Proteomic profiles of the pooled samples were compared, and approximately 800 protein spots were observed in each of the gels. Expression levels of four of the protein spots in active BD were significantly higher than those in the normal controls. Mass spectrometric protein identification revealed that the four protein spots corresponded to two proteins: haptoglobin (Hp) and serum amyloid A (SAA). Western blot and ELISA showed that Hp was only overexpressed in active BD but not in inactive BD, VKH syndrome, or healthy controls. An obvious band of SAA was detected in 72.2% of the serum samples from BD patients, whereas a vague band of this protein was found in 10.0% of the tested normal samples and 9.1% of VKH samples. Our results revealed a significantly increased expression of Hp and SAA in serum of active BD patients. These two proteins may be involved in the development of BD
IL-23 promotes CD4(+) T cells to produce IL-17 in Vogt-Koyanagi-Harada disease
Chi, W. ; Yang, P.Z. ; Li, B. ; Wu, C.Y. ; Jin, H.L. ; Zhu, X.F. ; Chen, L.N. ; Zhou, H.Y. ; Huang, X.K. ; Kijlstra, A. - \ 2007
Journal of Allergy and Clinical Immunology 119 (2007)5. - ISSN 0091-6749 - p. 1218 - 1224.
proinflammatory cytokine production - autoimmune inflammation - sympathetic ophthalmia - rheumatoid-arthritis - human keratinocytes - interferon-gamma - interleukin-17 - expression - lymphocytes - distinct
Background: Vogt-Koyanagi-Harada (VKH) disease is a systemic refractory autoimmune disease. IL-23 has been thought to play a critical role in autoimmune disease through inducing the development of IL-17-producing CD4(+) T cells. Objective: To investigate the expression of IL-23 and IL-17 and the influence of IL-23 on IL-17 production in patients with VKH disease. Methods: Blood samples were taken from 25 patients with VKH disease and 16 healthy controls. Peripheral blood mononuclear cells (PBMCs) were subjected to analysis of IL-23p19 mRNA and IL-23 protein expression using RT-PCR and ELISA, respectively. The IL-17 levels in the supernatants of PBMCs and CD4(+) T cells cultured in the absence or presence of recombinant (r)IL-23, rIL-12, or anti-IFN-gamma were determined by ELISA. Results: The patients with VKH disease with active uveitis showed an elevated level of IL-23p19 mRNA in PBMCs, higher IL-23 in the serum and supernatants of PBMCs, and increased production of IL-17 by polyclonally stimulated PBMCs and CD4+ T cells. Recombinant IL-23 significantly enhanced IL-17 production, whereas rIL-12 and IFN-gamma inhibited IL-17 production. More importantly, IL-17 production was significantly increased in patients with active uveitis in the presence of rIL-23. Both rIL-23 and rIL-12 enhanced IFN-gamma production. Conclusion: The results suggest that IL-23-stimulated production of IL-17 by CD4+ T cells may be responsible for the development of uveitis seen in patients with VKH disease. Clinical implications: This study provides a new insight into the mechanism involved in the development of VKH disease.
The impact of chronic diseases - The partner's perspective
Baanders, A.N. ; Heijmans, M.J.W.M. - \ 2007
Family and Community Health: the journal of health 30 (2007)4. - ISSN 0160-6379 - p. 305 - 317.
quality-of-life - chronic illness - rheumatoid-arthritis - prostate-cancer - serious illness - chronic pain - spouses - caregivers - families - burden
A chronic physical disease not only has direct consequences for the chronically ill person but can also distort the life of the healthy partner. This study of a representative sample of chronically ill persons and their partners in the Netherlands presents quantitative information on the proportion of partners who experience consequences in 4 distinguished areas (personal life strain, social relations, financial burden, and intrinsic rewards) and provides insight into the factors related to this. Data were derived from a subsample (N = 1,093) of participants in the Dutch Panel of Patients With Chronic Diseases. Linear regression analysis was used to determine the relative effect of caregiving and of disease characteristics to explain the variance in the 4 impact factors. The most prevailing consequences, experienced by more than half of the partners, were related to personal life strain and intrinsic rewards. An impact on social relations and financial situation was reported by 20% of the partners. The regression analyses showed that the time spent on caregiving is the main predictor for all 4 impact measures in this study. However, the findings also make clear that the impact on the partner's life does not arise entirely from the amount of caregiving. An independent effect of specific disease characteristics is observed in addition to the effect of caregiving; that is, we found that physical impairments in the patient are related to higher personal life strain and higher financial burden whereas social impairments are related to higher impact on all 4 factors. When the patient's disease is accompanied with fatigue, the partner reports higher impact on personal life, on social relations, and on intrinsic rewards, and pain significantly affects the partner's social relations. Partners of patients with cancer, musculoskeletal, or digestive disorders are more vulnerable for the consequences of the chronic disease. The impact on female partners is higher for all 4 impact factors. The findings make clear that living with a chronically ill person has an impact on the partner's life that goes beyond the consequences of caregiving.
Serum amyloid A isoforms in serum and synovial fluid in horses with lipopolysaccharide-induced arthritis
Jacobsen, S. ; Niewold, T.A. ; Halling-Thomsen, M. ; Nanni, S. ; Olsen, E. ; Lindegaard, C. ; Andersen, P.H. - \ 2006
Veterinary Immunology and Immunopathology 110 (2006)3-4. - ISSN 0165-2427 - p. 325 - 330.
rheumatoid-arthritis - local expression - saa protein - tissue - monocytes
The aim of the study was to determine the intraarticular set-Urn amyloid A (SAA) response pattern in horses with inflammatory arthritis. Inflammatory arthritis was induced by injection of lipopolysaccharide (LPS) into the radiocarpal joint of four horses. Serum and synovial fluid (SF) samples were collected before and at 4, 8, 12, 24, 48, 72, 96, and 144 h after injection. Concentrations of SAA were measured by immunoturbidometry, and expression of SAA isoforms was visualized by denaturing isoelectric focusing and Western blotting. The LPS injection caused systemic and local clinical signs of inflammation. Serum amyloid A appeared in serum and SF within 8 h after LPS injection. Isoelectric focusing showed three major SAA hands with apparent isoelectric points (pI) of 7.9, 8.6, and > 9.3 in serum and SF. Synovial fluid contained two additional isoforms with highly alkaline apparent pI values (apparent pl value extrapolated from standard curve = 10.0 and 10.2), which were not present in any of the serum samples. In conclusion, intraarticular injection of LPS induced systemic and local inflammatory responses in the horses. By demonstrating SF-specific SAA isoforms the results of the present Study suggest that SAA is synthesized locally in the equine inflamed joint, similar to what has been demonstrated in humans previously. The marked local SAA synthesis suggests an important pathophysiological role in inflammatory arthritis.
Role of T-cell receptor V beta 8.3 peptide vaccine in the prevention of experimental autoimmune uveoretinitis
Zhang, R. ; Yang, P.Z. ; Wu, C.Y. ; Jin, H.L. ; Li, B. ; Huang, X. ; Zhou, H. ; Gao, Y. ; Zhu, L. ; Kijlstra, A. - \ 2006
Chinese Medical Journal 119 (2006)9. - ISSN 0366-6999 - p. 740 - 748.
myelin basic-protein - multiple-sclerosis - rheumatoid-arthritis - cdr2 peptides - encephalomyelitis - disease - immunization - therapy - determinant - lymphocytes
T-cell receptor (TCR) plays an important role in the development of autoimmune diseases. Recently, it was reported that immunization of animals with TCR peptide derived from the pathogenic cells could prevent autoimmune diseases. The aim of this study was to investigate whether vaccination with a synthetic peptide from the hypervariable region of TCR V(beta) 8.3, an experimental autoimmune uveoretinitis (EAU)-associated gene, was able to prevent the disease. METHODS: EAU was induced in Lewis rats by immunization with IRBP R16 peptide emulsified in complete Freund's adjuvant (CFA). The clinical and histological appearances were scored. Delayed type hypersensitivity (DTH) and lymphocyte proliferation were detected. Cytokine levels of aqueous humour, supernatants of cells from spleen and draining lymph nodes were measured by enzyme linked immunosorbent assay (ELISA). Gene expression of TCR V(beta) 8.3 on CD(4)(+) T cells was examined by real time quantitative polymerase chain reaction (PCR). RESULTS: After vaccination, the intraocular inflammation was significantly mitigated, antigen specific DTH and lymphocyte proliferation responses were suppressed, interleukin (IL)-2 in aqueous humour, interferon (IFN)-gamma and IL-2 produced by the spleen and draining lymph node cells were significantly decreased, whereas the production of IL-4 and IL-10 were increased. The response of draining lymph node cells to TCR V(beta) 8.3 peptide was enhanced after vaccination. Inoculation with CFA alone did not affect the severity of EAU and the above parameters. The suppression of EAU was much stronger in the group of four fold inoculations than the group of two fold inoculations. The expression of TCR V(beta) 8.3 gene was significantly reduced in the group of fourfold inoculations. CONCLUSION: Vaccination with the synthetic TCR V(beta) 8.3 peptide could remarkably inhibit the development of EAU.
CD4+PD-1+T Cells Acting as Regulatory Cells during the Induction of Anterior Chamber-Associated Immune Devation
Meng, Q. ; Yang, P. ; Li, B. ; Zhou, H. ; Huang, X. ; Zhu, L. ; Ren, Y. ; Kijlstra, A. - \ 2006
Investigative ophthalmology and visual science 47 (2006)10. - ISSN 0146-0404 - p. 4444 - 4452.
death-1 pd-1 pathway - responses in-vivo - b7 family - rheumatoid-arthritis - allograft survival - th2 cells - expression - eye - tolerance - privilege
To study the expression and functional characteristics of programmed death-1 (PD-1) and its ligands in the spleens of mice undergoing anterior chamber-associated immune deviation (ACAID). METHODS: ACAID was induced in BALB/c mice by intracameral injection of ovalbumin (OVA). The expression of PD-1 and its ligands in the spleens of ACAID mice was determined by quantitative real-time PCR, Western blotting, and flow cytometry. In vitro proliferation assays, enzyme-linked immunosorbent assays, and adoptive transfer assays were used to investigate the functional characteristics of splenic CD4+PD-1+ T cells of ACAID mice. RESULTS: Both mRNA and protein of PD-1, PD-L1, and PD-L2 were markedly upregulated in the spleens of ACAID mice compared with controls. CD4+PD-1+ T cells from ACAID mice produced large amounts of IL-10 and exhibited in vitro antigen-specific suppressive activity. CD4+PD-1+ T cells from ACAID mice were able to significantly inhibit the antigen-specific, delayed-type hypersensitivity response when adoptively transferred to naive mice. CONCLUSIONS: CD4+PD-1+ T cells from ACAID mice, as regulatory cells, are involved in the induction of antigen-specific suppression in association with enhanced expression of IL-10. CD4+PD-1+ T cells in the murine spleen may represent a substantial population of regulatory T cells possibly responsible for the induction of ACAID after intracameral injection of antigen.
Gluten: a two-edged sword. Immunopathogenesis of celiac disease
Koning, F. de; Gilissen, L.J.W.J. ; Wijmenga, C. - \ 2005
Springer Seminars in Immunopathology 27 (2005)2. - ISSN 0344-4325 - p. 217 - 232.
t-cell epitope - small-intestinal mucosa - ctla4/cd28 gene region - wide linkage analysis - tissue transglutaminase - susceptibility loci - molecular characterization - binding characteristics - confers susceptibility - rheumatoid-arthritis
Celiac disease (CD) is a small intestinal disorder caused by adaptive and innate immune responses triggered by the gluten proteins present in wheat. In the intestine, gluten is partially degraded and modified, which results in gluten peptides that bind with high affinity to HLA-DQ2 or HLA-DQ8 and trigger an inflammatory T cell response. Simultaneously, gluten exposure leads to increased production of IL15, which induces the expression of NKG2D on intraepithelial lymphocytes and its ligand MICA on epithelial cells, leading to epithelial cell destruction. The gluten-specific T cell response results in the production of antibodies against tissue transglutaminase and these are specific indicators of disease. CD is one of the most common inherited diseases, the HLA-DQ locus being the major contributing genetic factor. However, as the inheritance does not follow a Mendelian segregation pattern, multiple other genes, each with relative weak effect, contribute to disease development. An important role for environmental factors, however, can not be ignored as the concordance rate in monozygous twins is considerably less than 100%. The identification of these environmental factors and susceptibility genes may allow a better understanding of disease etiology and provide diagnostic and prognostic markers. The current treatment for CD consists of a life-long gluten-free diet. Although long thought to be impossible, recent results suggest that the development of nontoxic wheat varieties may be feasible, which would aid disease prevention and provide an alternative food source for patients.
Angiopoietin-like-4 is a potential angiogenic mediator in arthritis
Hermann, L.M. ; Pinkerton, M. ; Jennings, K. ; Yang, L. ; Grom, A. ; Sowders, D. ; Kersten, A.H. ; Witte, D.P. ; Hirsch, R. ; Thornton, S. - \ 2005
Clinical Immunology 115 (2005)1 sp. is.. - ISSN 1521-6616 - p. 93 - 101.
collagen-induced arthritis - endothelial growth-factor - necrosis-factor-alpha - rheumatoid-arthritis - gene-transfer - target gene - expression - inhibition - protein - vegf
Our previous studies of gene expression profiling during collagen-induced arthritis (CIA) indicated that the putative angiogenic factor Angptl4 was one of the most highly expressed mRNAs early in disease. To investigate the potential involvement of Angptl4 in CIA pathogenesis, Angptl4 protein levels were assessed at early stages of disease and its cellular sources were determined. In addition, the functional effects of mouse Angptl4 on endothelial cells were assessed. Angptl4 protein levels were higher in arthritic joints as compared to normal joints. In situ hybridization localized Angptl4 mRNA to stromal fibroblast-like cells within the inflamed synovium. Temporal expression of Angptl4 mRNA during CIA was similar to that of key angiogenic factors, including structurally related angiopoietin 1. Recombinant mouse Angptl4 promoted endothelial cell survival and formation of tubule-like structures. These functional effects of Angptl4, combined with very high expression at early stages of CIA, suggest a role for Angptl4 in angiogenesis in arthritis
Influence of Growth Conditions and Developmental Stage on N-Glycan Heterogeneity of Transgenic Immunoglobulin G and Endogenous Proteins in Tobacco Leaves
Elbers, I.J.W. ; Stoopen, G.M. ; Bakker, H. ; Stevens, L.H. ; Bardor, M. ; Molthoff, J.W. ; Jordi, W.J.R.M. ; Bosch, H.J. ; Lommen, A. - \ 2001
Plant Physiology 126 (2001). - ISSN 0032-0889 - p. 1314 - 1322.
rheumatoid-arthritis - leaf senescence - plant-cells - glycosylation - antibodies - igg - oligosaccharides - biosynthesis - glycoproteins - expression
Plants are regarded as a promising system for the production of heterologous proteins. However, little is known about the influence of plant development and growth conditions on N-linked glycosylation. To investigate this, transgenic tobacco (Nicotiana tabacum cv Samsun NN) plants expressing a mouse immunoglobulin G antibody (MGR48) were grown in climate rooms under four different climate conditions, i.e. at 15°C and 25°C and at either low or high light conditions. N-glycans on plantibodies and soluble endogenous proteins were analyzed with matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS). Antibodies isolated from young leaves have a relatively high amount of high- mannose glycans compared with antibodies from older leaves, which contain more terminal N-acetylglucosamine. Senescence was shown to affect the glycosylation profile of endogenous proteins. The relative amount of N-glycans without terminal N-acetylglucosamine increased with leaf age. Major differences were observed between glycan structures on endogenous proteins versus those on antibodies, probably to be attributed to their subcellular localization. The relatively high percentage of antibody N-glycan lacking both xylose and fucose is interesting