bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic and prognostic values of anti glucose-6-phosphate isomerase antibodies in community-recruited patients with very early arthritis
Authors: JOUEN F , VITTECOQ O , LEGUILLOU F , TABTI-TITON I , MENARD J F , MEJJAD O , POUPLIN S , BOUMIER P , FARDELLONE P , GAYET A , GILBERT D , TRON F , LE LOËT X 
Published: August 2004

SUMMARYThe objective of this study was to determine the diagnostic and prognostic values of antiglucose-6-phosphate isomerase (GPI) antibodies in patients with very early arthritis. Anti-GPI antibodies were measured by ELISA using purified GPI from rabbit muscle in: (i) 383 sera from healthy blood donors (n = 120), well-established rheumatoid arthritis (RA) (n = 99) and non-RA differentiated arthritis (NRADA) (n = 164) patients; (ii) 195 sera obtained from community-recruited patients with very early inflammatory arthritis (VErA cohort) that were studied for 1 year and classified as having RA (n = 116), NRADA (n = 41), and undifferentiated arthritis (UA) (n = 38) after the follow-up period. The criterion for severity was the progression of radiographic damage. Prevalence of anti-GPI antibodies was significantly higher in well-established RA patients (45·4%) compared to healthy subjects (2·5%). Anti-GPI antibodies were also present in sera from NRADA: systemic lupus erythematosus 53%, polymyositis 45·4%, adult-onset Still's disease 44%, systemic sclerosis 42·8%, spondylarthropathies 25% and primary Sjögren’s syndrome 5·8%. No significant association was found between the presence of anti-GPI antibodies and the 3 diagnostic groups from the VErA cohort. No correlation was observed between anti-GPI and autoantibodies usually associated with RA. Anti-GPI antibodies were not predictive of radiological progression in patients with very early arthritis. Thus, anti-GPI antibodies are not useful for discriminating RA from non-RA rheumatic diseases and do not constitute a predictive factor of structural damage.
Superiority of thyroid peroxidase DNA over protein immunization in replicating human thyroid autoimmunity in HLA-DRB1*0301 (DR3) transgenic mice
Authors: FLYNN J C , GARDAS A , WAN Q , GORA M , ALSHARABI G , WEI W Z , GIRALDO A A , DAVID C S , KONG Y M , BANGA J P 
Published: August 2004

SUMMARYMurine experimental autoimmune thyroiditis (EAT), characterized by thyroid destruction after immunization with thyroglobulin (Tg), has long been a useful model of organ-specific autoimmune disease. More recently, porcine thyroid peroxidase (pTPO) has also been shown to induce thyroiditis, but these results have not been confirmed. When (C57BL/6 × CBA)F1 mice, recently shown to be susceptible to mouse TPO-induced EAT, were immunized with plasmid DNA to human TPO (hTPO) and cytokines IL-12 or GM-CSF, significant antibody (Ab) titres were generated, but minimal thyroiditis was detected in one mouse only from the TPO + GM-CSF immunized group. However, after TPO DNA immunization of HLA-DR3 transgenic class II-deficient NOD mice, thyroiditis was present in 23% of mice injected with TPO + IL-12 or GM-CSF. We also used another marker for assessing the closeness of the model to human thyroid autoimmunity by examining the epitope profile of the anti-TPO Abs to immunodominant determinants on TPO. Remarkably, the majority of the anti-TPO Abs was directed to immunodominant regions A and B, demonstrating the close replication of the model to human autoimmunity. TPO protein immunizations of HLA-DR3 transgenic mice with recombinant hTPO did not result in thyroiditis, nor did immunization of other mice expressing HLA class II transgenes HLA-DR4 or HLA-DQ8, with differential susceptibility to Tg-induced EAT. Moreover, our efforts to duplicate exactly the experimental procedures used with pTPO also failed to induce thyroiditis. The success of hTPO plasmid DNA immunization of DR3+ mice, similar to our reports on Tg-induced thyroiditis and thyrotropin receptor DNA-induced Graves’ hyperthyroidism, underscores the importance of DR3 genes for all three major thyroid antigens, and provides another humanized model to study autoimmune thyroid disease.
Faster activation of polymorphonuclear neutrophils in resistant mice during early innate response toPseudomonas aeruginosalung infection
Authors: JENSEN P Ø , MOSER C , KOBAYASHI O , HOUGEN H P , KHARAZMI A , HØIBY N 
Published: August 2004

SUMMARYPolymorphonuclear neutrophils (PMNs) are crucial for the outcome of Pseudomonas aeruginosa lung infection in patients with cystic fibrosis. We compared PMNs and inflammatory cytokines in the lungs and blood from susceptible BALB/c and resistant C3H/HeN mice 1 and 2 days after intratracheal challenge with alginate embedded P. aeruginosa. These parameters were correlated with the quantitative bacteriology and histopathology of the lungs. After challenge, the content of granulocyte colony-stimulating factor (G-CSF) and macrophage inflammatory protein-2 (MIP-2) was increased in the lungs and the sera and the percentage of PMNs was increased in the blood. However, 2 days after challenge the concentration of G-CSF and MIP-2 was higher in the lungs and sera of BALB/c mice. CD11b expression was higher on the PMNs of the C3H/HeN mice. The expression of CD62L on PMNs of both strains of mice was decreased 1 day after bacterial challenge, whereas the expression was increased after 2 days of challenge on PMNs of C3H/HeN mice only. These changes were accompanied by a more severe lung inflammation in BALB/c mice and faster clearance of the bacteria in C3H/HeN mice. In conclusion, the rapid early bacterial clearance in the lungs of C3H/HeN mice could be explained by faster activation of the PMNs, as indicated by the higher up-regulation of CD11b. The severe lung inflammation in BALB/c mice may be caused by the early higher content of G-CSF in the sera mobilizing PMNs from the bone marrow and the persistent chemotactic gradient provided by MIP-2 in the lungs.
Suppressive effect of leflunomide metabolite (A77 1726) on metalloproteinase production in IL-1β stimulated rheumatoid synovial fibroblasts
Authors: MIGITA K , MIYASHITA T , ISHIBASHI H , MAEDA Y , NAKAMURA M , YATSUHASHI H , IDA H , KAWAKAMI A , AOYAGI T , KAWABE Y , EGUCHI K 
Published: August 2004

SUMMARY
Leflunomide, an isoxazol derivative structurally unrelated to other immunomodulatory drugs, has proven to be efficacious in the treatment of rheumatoid arthritis (RA). This study was conducted to elucidate the mechanism by which leflunomide mediated antirheumatic effects. We investigated the effects of A77 1726, leflunomide's active metabolite, on mitogen-activated protein kinase (MAPK) activation in IL-1β-stimulated rheumatoid synovial fibroblasts. The effects of A77 1726 on the secretion of matrix metalloproteinases (MMPs) from rheumatoid synovial fibroblasts were also examined. A77 1726 partially suppressed IL-1β-induced ERK1/2 and p38 kinase activation. In contrast, A77 1726 efficiently suppressed IL-1β-stimulated JNK1/2 kinase activation. Although no suppressive effect was demonstrated on MMP-2, A77 1726 markedly inhibited MMP-1, 3, and 13 secretions from IL-1β-stimulated rheumatoid synovial fibroblasts. Tissue inhibitor of metalloproteinases-1 (TIMP-1) was constitutively produced from rheumatoid synovial fibroblasts and the suppressive effects of A77 1726 on TIMP-1 production were minimal. Our results suggest that the suppression of the MAPK signalling pathway and MMP synthesis in rheumatoid synovial fibroblasts is a possible mechanism for the inhibitory activity of leflunomide against rheumatoid arthritis.
Amelioration of lupus manifestations by a peptide based on the complementarity determining region 1 of an autoantibody in severe combined immunodeficient (SCID) mice engrafted with peripheral blood lymphocytes of systemic lupus erythematosus (SLE) patients
Authors: MAUERMANN N , STHOEGER Z , ZINGER H , MOZES E 
Published: August 2004

SUMMARYA peptide based on the complementarity determining region (CDR)1 of a human monoclonal anti-DNA autoantibody (hCDR1) was shown to either prevent or treat an already established murine lupus in systemic lupus erythematosus (SLE)-prone mice or in mice with induced experimental SLE. The present study was undertaken to determine the therapeutic potential of hCDR1 in a model of lupus in severe combined immunodeficient (SCID) mice engrafted with peripheral blood lymphocytes (PBL) of patients with SLE. To this end, PBL obtained from lupus patients were injected intraperitoneally into two equal groups of SCID mice that were treated either with the hCDR1 (50 µg/mouse) once a week for 8 weeks, or with a control peptide. Mice were tested for human IgG levels, anti-dsDNA autoantibodies, anti-tetanus toxoid antibodies and proteinuria. At sacrifice, the kidneys of the successfully engrafted mice were assessed for human IgG and murine complement C3 deposits. Of the 58 mice transplanted with PBL of SLE patients, 38 (66%) were engrafted successfully. The mice that were treated with the control peptide developed human dsDNA-specific antibodies. Treatment with hCDR1 down-regulated the latter significantly. No significant effect of the treatment on the levels of anti-tetanus toxoid antibodies could be observed. Treatment with hCDR1 resulted in a significant amelioration of the clinical features manifested by proteinuria, human IgG complex deposits as well as deposits of murine complement C3. Thus, the hCDR1 peptide is a potential candidate for a novel specific treatment of SLE patients.
Relationship between serum levels of IL-18 and IgG1 in patients with primary Sjögren's syndrome, rheumatoid arthritis and healthy controls
Authors: ERIKSSON P , ANDERSSON C , EKERFELT C , ERNERUDH J , SKOGH T 
Published: August 2004

SUMMARYPrimary Sjögren's syndrome (SS) is characterized by inflammation in salivary and lachrymal glands, with a local predominance of Th1-like cytokines, as well as the pleiotropic cytokine interleukin (IL) 18. High serum levels of polyclonal IgG are common, with a subclass imbalance in which IgG1 is increased and IgG2 is normal or low. IL-18 is also of pathogenetic importance in rheumatoid arthritis. In the present study we looked for any relationship between serum IL-18 as well as transforming growth factor (TGF) β1 versus IgA, IgM, and IgG subclass levels in SS (n = 16), rheumatoid arthritis (RA) (n = 15), and healthy controls (n = 15). SS was defined by the revised American-European classification criteria. IL-18 and TGF-β1 were analyzed with enzyme immunoassays (EIA), and IgG1, IgG2 and IgG3 by single radial immunodiffusion. In the composite group of RA, SS and normal controls, IgG1 and IL-18 were related (R = 0·52, P = 0·0005). No relation was found neither between IL-18 versus IgG2, IgG3 or IgA, nor between serum TGF-β1 versus any of the immunoglobulins. Since serum levels of IL-18 are related to serum IgG1, IL-18 may be of importance for IgG1 switch and/or release.
Excitatory amino acids, TNF-α, and chemokine levels in synovial fluids of patients with active arthropathies
Authors: MCNEARNEY T , BAETHGE B A , CAO S , ALAM R , LISSE J R , WESTLUND K N 
Published: August 2004

SUMMARY
The aim of this study was to assess the synovial fluid (SF) neurotransmitter excitatory amino acid (EAA) levels, including glutamate (Glu) and aspartate (Asp), in the context of SF levels of other amino acids, TNF-α and chemokines from patients with active arthropathies. The SF was collected from patients with active rheumatoid arthritis (RA), gout, or osteoarthritis (OA). The SF samples were analysed for levels of neurotransmitters glutamate and aspartate, tumour necrosis factor-alpha (TNF-α), Regulated upon Activation Normally T-cell Expressed and Secreted (RANTES), macrophage inhibitory factor-1 alpha (MIP-1α) and interleukin 8 (IL-8). SF WBC counts were also determined. Correlations between SF EAA, TNF-α and chemokines were determined by the Pearson product-moment correlation. Primary cultures derived from SF from active RA and gout patients were incubated with added l-glutamate, to assess if exposure to Glu could increase TNF-α levels. There were significant elevations in SF EAA, SF TNF-α and SF RANTES in RA patients compared to gout or OA patients. Significant correlations between SF EAA and SF RANTES, MIP-1α and IL-8 levels were seen, and SF EAA and SF TNF-α or SF WBC levels approached significance. Addition of exogenous neurotransmitter glutamate significantly increased TNF-α levels in primary cell cultures derived from RA and gout patients. The SF neurotransmitter EAA levels significantly correlated to selected SF chemokine levels, in clinically active RA, gout and OA patients, independent of disease. Added Glu resulted in significantly increased TNF-α levels in primary synovial cell cultures. These data expand the relationship of SF neurotransmitter EAA levels to SF cytokines and chemokines in patients with clinically active arthritis, and suggest that neurotransmitters Glu and Asp contribute to peripheral inflammatory processes.
Cytokine expression pattern in the genital tract ofChlamydia trachomatispositive infertile women – implication for T-cell responses
Authors: REDDY B S , RASTOGI S , DAS B , SALHAN S , VERMA S , MITTAL A 
Published: August 2004

SUMMARYHuman genital infection caused by Chlamydia trachomatis is thought to be immunologically mediated, resulting in local recruitment of lymphocyte subsets and inducing the production of cytokines. Little information is available about the role of lymphocyte recruitment and the regulation of cytokine production in the genital tract of C. trachomatis positive infertile women. We have evaluated the recruitment of lymphocyte subsets in the genital tract and production of Th1/Th2 cytokines in cervical secretions and laparoscopic specimens from the fallopian tubes of C. trachomatis positive infertile women (n = 17) and compared them with controls, viz. C. trachomatis negative infertile women (n = 20) using ELISA and flow cytometry. None of these patients were found to be infected either with Candida sps., bacterial vaginosis, Trichomonas vaginalis, Neisseria gonorrhoeae, Mycoplasma hominis or Ureaplasma urealyticum in the cervix. Flow cytometric analysis of cervical secretions in Chlamydia positive women revealed recruitment of both CD4 and CD8 lymphocytes to the genital tract was up-regulated and a variation in the production rates of different cytokines in cervical secretions and fallopian tube was observed. We found that the immune responses in cervical secretions were of Th0 type, since all the analysed cytokines, viz. IFN-γ, TNF-α, IL-10 and IL-12 were up-regulated. As, both CD4 and CD8 cells contribute to the production of IFN-γ and IL-10, these results suggest that along with CD4 cells, CD8 lymphocytes also may be important for local regulation of Th1/Th2 responses in the genital tract during C. trachomatis infection.
Human macrophages kill human mesangial cells by Fas-L-induced apoptosis when triggered by antibody via CD16
Authors: BOYLE J J 
Published: August 2004

SUMMARY
Glomerulonephritis may be triggered by antibody deposits that activate macrophages to promote tissue damage. Macrophage-induced apoptosis of human vascular smooth muscle cells and rodent mesangial cells is potentially relevant to glomerulonephritis. Therefore, studies of macrophage-induced apoptosis were extended to antibody-activated macrophages. That is, we studied antibody dependent cellular cytotoxicity (ADCC). To corroborate results, we studied biochemical versus microscopic measurements, soluble or immobilized immunoglobulin and vascular smooth muscle cells (VSMCs) or mesangial cells (MCs). U937 macrophages and human peripheral blood macrophages provoked antibody-dependent killing of MCs and VSMCs. Macrophage-induced death was apoptotic based on electron microscopy, annexin-V, activated caspase-3 and hypodiploid DNA. ADCC was inhibited by antagonistic antibodies to Fas-L and to CD16 (Fc-γ-RIII) but not to CD64 (Fc-γ-RI). In conclusion, antibody-dependent killing of human MCs by human macrophages was via Fas-L and CD16.
Methotrexate reduces antibody responses to recombinant humanα-galactosidase A therapy in a mouse model of Fabry disease
Authors: GARMAN R D , MUNROE K , RICHARDS S M 
Published: August 2004

SUMMARYTherapeutic enzymes are often recognized as foreign by the immune system of patients undergoing enzyme replacement therapy. The antibodies that develop may alter pharmacokinetics and biodistribution of the therapeutic protein, may be able to neutralize the activity of the enzyme, or may cause immune reactions in certain patients. We have explored treatment regimens to reduce the antibody response to human α-galactosidase A (r-hαGAL) in Fabry (αGAL knock-out) and normal BALB/c mice. A wide variety of treatment modalities were tested, including high dose tolerance induction, increased frequency of therapeutic doses and immunosuppressive drugs in combination with administration of enzyme. The most substantial effects were observed in mice injected intravenously with r-hαGAL in combination with methotrexate (MTX), which significantly lowered r-hαGAL-specific serum antibody levels. A short course of treatment with MTX was able to reduce antibody and spleen cell proliferative responses to long-term r-hαGAL treatment. MTX was able to suppress the development of r-hαGAL-specific IgG in antigen-primed mice. However, MTX was not effective in dampening robust ongoing antibody responses. These experiments provide a framework for the design of clinical protocols to prevent the drug-specific antibody responses of patients undergoing enzyme replacement therapy.
Interactions among human immunodeficiency virus (HIV)-1, interferon-γand receptor of activated NF-κB ligand (RANKL): implications for HIV pathogenesis
Authors: FAKRUDDIN J M , LAURENCE J 
Published: August 2004

SUMMARYWe reported recently that exposure of human T cells to soluble HIV-1 envelope glycoprotein gp120 induced biologically active tumour necrosis factor (TNF)-α-related cytokine receptor of activated NF-κB ligand (RANKL), the primary drive to osteoclast differentiation and bone resorption. Furthermore, certain anti-HIV protease inhibitors linked clinically to accelerated bone loss in HIV disease blocked the physiological control of RANKL activity by interferon (IFN)-γ through inhibition of degradation of the RANKL nuclear adapter signalling protein, TNF receptor associated protein 6 (TRAF6). We now report a series of reciprocal interactions among HIV-1, RANKL and IFN-γ. RANKL augmented HIV replication in acutely and chronically infected cells of T lymphocyte and monocyte lineage, effects which occurred at a transcriptional level in conjunction with activation of NF-κB. TNF-α and RANKL were markedly synergistic in induction of HIV. Low pharmacological levels of IFN-γ (0·75–3 ng/ml) suppressed RANKL-driven enhancement of HIV replication, as did L-T6DP-1, a cell-permeable peptide inhibitor of TRAF6. In contrast, HIV replication induced by TNF-α and phorbol ester were not inhibited, and in some cases augmented, by IFN-γ. We conclude that a positive feedback loop exists between RANKL production and HIV replication, which may be relevant to both the pathophysiology of HIV-linked osteopenia and control of HIV growth. This pathway appears distinct from those of other cytokine activators of HIV, with respect to its utilization of TRAF6 and its suppression by IFN-γ. These data raise the possibility that TRAF-specific inhibitory peptides, alone or in conjunction with IFN-γ, could be used to regulate HIV activation in vivo.
Immune complex-stimulated production of interleukin-12 in peripheral blood mononuclear cells is regulated by the complement system
Authors: TEJDE A , MATHSSON L , EKDAHL K N , NILSSON B , RÖNNELID J 
Published: August 2004

SUMMARYImmune complexes (IC) can induce cytokine production in vitro. While immune aggregates (IA) consisting of heat-aggregated gamma globulin (HAGG) as model IC increased interleukin (IL)-10 levels in cell cultures with native human serum, IL-12p40/p70 production was inhibited. Three series of experiments suggested that the effects of IA on IL-12 production depended on a functionally intact complement system: (1) heat-inactivation of serum inverted the inhibitory effect of IA on IL-12p40/p70 production; (2) IA-induced IL-12p40 production in a C4 deficient serum was lowered by addition of C4; and (3) addition of the peptide compstatin, which blocks C3 activation, mimicked the effects of heat inactivation on IL-12p40 levels. Neutralization of IL-12 resulted in modestly increased IL-10 levels, while neutralization of IL-10 had no effects on IL-12p40 production. IA-induced production of IL-10 was partially blocked by anti-Fcγ RII antibodies, whereas Fcγ R or CR blockade had no effect on IL-12p40 production. IC and local or systemic complement activation characterize rheumatoid arthritis, systemic lupus erythematosus and many malignancies. Different and complement-dependent effects on the production of IL-10 and IL-12 can be of importance in these diseases, where control of the complement system might be a way to direct IC-induced cytokine production in either a type 1 or type 2 direction.
Interleukin-16 expression and release in bullous pemphigoid
Authors: FREZZOLINI A , CIANCHINI G , RUFFELLI M , CADONI S , PUDDU P , DE PITÀ O 
Published: August 2004

SUMMARYCutaneous infiltration of activated CD4+ T cells and eosinophils is an early event in blister formation during bullous pemphigoid (BP), suggesting that the trafficking of circulating leucocytes through the sites of inflammation, their activation and cytokine release is crucial in the pathogenesis of the disease. IL-16 is a major chemotactic factor able to recruit CD4+ cells in the skin during inflammation and to induce the expression of functional high-affinity interleukin (IL)-2 receptors, thus contributing to cellular activation and proliferation. We performed a study in order to evaluate the presence of IL-16 in skin samples and sera and blister fluids of patients affected with BP in active phase of the disease (n = 39), compared with healthy donors studied as control group. Ten patients were also evaluated before and after steroid therapy. Our results demonstrated that IL-16 was expressed strongly by keratinocytes and by dermal infiltrating CD4+ T lymphocytes in lesional skin of BP patients. High levels of IL-16 were detected in sera and blisters of BP, significantly higher in respect to healthy donors. When patients were investigated for the presence of eosinophil cationic protein (ECP) and soluble CD30 (sCD30) to reveal signs of eosinophils and Th2-cells activation, we found a positive correlation between IL-16 serum levels and both ECP and sCD30, suggesting that IL-16 is involved in Th2 lymphocytes and eosinophils recruitment during BP.