bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cross-reactivity of anti-galactocerebroside autoantibodies with aTrypanosoma bruceiproteolipidic epitope
Authors: Girard M , Bisser S , Buscher P , Bouteille B , Preud’Homme J-L , Jauberteau M-O 
Published: March 2003

SUMMARYPathogenic mechanisms of the demyelinating encephalopathy featuring the nervous phase of human African trypanosomiasis (HAT) are largely unknown. They might include autoimmune disorders. A variety of autoantibodies is detected during the disease and we have previously evidenced anti-galactocerebroside (GalC) antibodies in the serum and cerebrospinal fluid (CSF) from patients in the nervous stage (stage II) of HAT. We now show that anti-GalC antibodies recognize an antigen located on the parasite membrane and common to different strains of trypanosomes. By using affinity chromatography with a rabbit anti-GalC antiserum, a 52-kD proteolipid was isolated from the membrane of Trypanosoma brucei (T. b.) brucei AnTat 1.9, AnTat 1.1E, and T. b. rhodesiense Etat 1.2/R and Etat 1.2/S. Antibodies directed against this antigen were found in the CSF from patients with nervous stage HAT. These CSF also contained anti-GalC antibodies and adsorption with the proteolipid decreased anti-GalC reactivity. Immunization of mice with this antigen induced the production of antibodies which cross-reacted with GalC but no protection from experimental infection with T. b. brucei. These data support the hypothesis that anti-GalC antibodies detected in the CSF from HAT patients might be induced by molecular mimicry with a parasite antigen.
The antagonism of interferon-gamma (IFN-γ) by heparin: examination of the blockade of class II MHC antigen and heat shock protein-70 expression
Authors: Fritchley S J , Kirby J A , Ali S 
Published: March 2003

SUMMARYIFN-γ is a pleiotropic cytokine that is primarily involved in the regulation of immune cell activation and the development of tissue inflammation. It is capable of activating a range of non-immune cells, including those of the vascular endothelium. These cells respond by increasing the expression of intracellular and cell-surface molecules such as class II MHC antigens and adhesion molecules that, together, increase the tendency for interaction with immune cells. It is known that IFN-γ can bind cell surface and extracellular heparan sulphate. Furthermore, soluble heparin can inhibit the function of this cytokine, presumably by competitive displacement from the cell surface, resulting in the failure of normal receptor signal transduction. In this study it is shown that heparin can prevent normal induction of the class II transactivator and heat shock cognate protein-70 in an IFN-γ-treated endothelial cell line. Both of these molecules are dependent on the activation of intracytoplasmic STAT-1, which is the most receptor proximal component of their respective induction pathways. This provides further evidence for the blockade by heparin of ligand activation of the specific IFN-γ receptor.
Selective expansion of T cells in gingival lesions of patients with chronic inflammatory periodontal disease
Authors: Yamazaki K , Nakajima T , Ohsawa Y , Tabeta K , Yoshie H , Sakurai K , Seymour G J 
Published: March 2003

SUMMARYChronic inflammatory periodontal diseases are characterized by a cellular infiltrate and are similar in many respects to other chronic inflammatory diseases. While periodontopathic bacteria have been recognized as the principal causative agent and the immune response to these bacteria is thought to be responsible for the tissue destruction, the full aetiological spectrum is still incompletely understood. In addition to many cell types such as polymorphonuclear leucocytes and macrophages, T cells have been implicated in pathogenesis and are considered to have regulatory roles in progression of the disease. Based on our recent studies demonstrating biased expression of several Vβ families in periodontitis tissues, the aim of this study was to characterize further the T cells relevant to the disease process by reverse transcription-polymerase chain reaction-single-strand conformation polymorphism (RT-PCR-SSCP) and subsequent nucleotide sequence analysis of complementarity-determining region 3 (CDR3) of the TCR β-chain. In spite of the likely involvement of numerous bacteria, the present study has clearly shown the oligoclonality of infiltrating T cells in periodontitis lesions in contrast to low clonality of peripheral blood T cells as evidenced by the appearance of distinct bands in gingival tissue samples and smear pattern of peripheral blood on SSCP gels. These were confirmed by the DNA sequencing of the CDR3 of Vβ16 of selected samples. The analysis of deduced amino acid sequences demonstrated amino acid motifs in the CDR3 region of the periodontitis lesion-derived sequences from each patient. The results indicate that gingival tissue-infiltrating T cells recognizing a limited number of antigens or epitopes are involved in the disease process.
An autoantibody targeting glycated IgG is associated with elevated serum immune complexes in rheumatoid arthritis (RA)
Authors: Tai A W-H , Newkirk M M 
Published: March 2003

SUMMARY
Advanced glycation end-products (AGE) play a role in diabetes complications and in RA. An autoantibody to IgG-AGE has been shown to correlate with RA disease activity. Thus we sought to analyse serum immune complexes (IC) and AGE-modified proteins in Caucasians and North American Indians to see if the presence of anti-IgG-AGE influenced their composition. Polyethylene glycol precipitation of IC from the serum of anti-IgG-AGE-positive or -negative RA patients, and healthy and diabetic controls were examined. Concentrations of circulating IC were highest in anti-IgG-AGE+ RA patients, followed by anti-IgG-AGE− RA patients, which were greater than healthy controls. IC amounts in the Ojibwe were consistently higher than in Caucasians. Affinity purification of AGE-modified proteins from IC and immunoblotting with antibodies against Ig γ and μ heavy chains, κ and λ light chains, and AGE Nε(carboxymethyl)lysine and imidazolone yielded similar results: anti-AGE+ RA patients had elevated levels relative to those without the autoantibody. Levels in both RA groups were higher than in controls. Glycated albumin amounts followed a similar distribution, but were not influenced by the presence of anti-AGE antibodies. A heavily glycated κ-chain was present primarily in IC from anti-IgG-AGE+ patients. These studies indicate that anti-AGE antibodies have a direct impact on the accumulation of IgG-AGE but not glycated albumin, and may block the normal clearance of IgG-AGE through AGE receptors.
The role of Fcγreceptor polymorphisms and C3 in the immune defence againstNeisseria meningitidisin complement-deficient individuals
Authors: Fijen C A P , Bredius R G M , Kuijper E J , Out T A , De Haas M , De Wit A P M , Daha M R , Van De Winkel J G J 
Published: March 2003

SUMMARYIndividuals with either a late (C5–9) complement component deficiency (LCCD) or properdin deficiency are at increased risk to develop meningococcal disease, often due to serogroups W135 and Y. Anti-meningococcal defence in both LCCD persons and properdin-deficient individuals without bactericidal antibodies depends mainly on phagocytosis. Three types of opsonin receptors are involved in phagocytosis by polymorphonuclear cells (PMN). These represent the polymorphic FcγRIIa (CD32) and FcγRIIIb (CD16b) receptors, and the C3 receptor CR3 (CD11b/CD18). When the distribution of FcγRIIa and FcγRIIIb allotypes was assessed in 15 LCCD and in 15 properdin-deficient patients with/without previous meningococcal disease, we found the combination of FcγRIIa-R/R131 with FcγRIIIb-NA2/NA2 allotypes to be associated with previous meningococcal disease (odds ratio 13·9, Fisher’s test P = 0·036). No such relation was observed in the properdin-deficient patients. The importance of FcγRIIa allotypes was also demonstrated using in vitro phagocytosis assays. PMN from FcγRIIa-R/R131 homozygous donors internalized IgG2 opsonized meningococci W135 significantly (P &lt; 0·05) less than PMN from FcγRIIa-H/H131 donors. When properdin-deficient serum was tested, it was observed that reconstitution with properdin resulted in enhanced PMN phagocytosis of the W135 meningococci (P = 0·001). This enhanced phagocytosis was parallelled by an increase in C3 deposition onto the opsonized meningococci W135 (r = 0·6568, P = 0·01). We conclude that the occurrence of meningococcal disease in LCCD patients is associated with certain FcγR allotypes. Properdin-deficient individuals are susceptible to meningococcal disease because of an insufficient C3 deposition on the surface of meningococci, resulting in insufficient phagocytosis.
Differential regulation of nitric oxide synthase isoforms in experimental acute Chagasic cardiomyopathy
Authors: Chandrasekar B , Melby P C , Troyer D A , Freeman G L 
Published: March 2003

SUMMARYWe have previously demonstrated induction and high level expression of IL-1β, IL-6 and tumour necrosis factor-alpha in the myocardium during the acute stage of experimental Trypanosoma cruzi infection (Chagas' disease). The myocardial depressive effects of these cytokines are mediated in part by the induction of nitric oxide synthase (NOS), production of nitric oxide (NO) and formation of peroxynitrite. In this study we investigated the expression, activity and localization of NOS isoforms, and the levels of NO, malondialdehyde (a measure of oxidative stress), and peroxynitrite in rats at 1·5, 5, 10 and 15 days after infection with T. cruzi trypomastigotes. The myocardial inflammatory infiltrate and number of amastigote nests increased over the course of infection. A significant increase in tissue nitrate + nitrite levels, NOS2 mRNA, and NOS2 enzyme activity was observed at all time points in the infected compared with uninfected animals. The enzyme activity of constitutive NOS, tissue malondialdehyde levels, and NOS3 mRNA levels was only transiently increased after infection. The protein levels of the NOS isoforms paralleled their mRNA expression. While no positive nitrotyrosine immunoreactivity was detected in control myocardium, its levels increased in infected animals over time. Thus, by 1·5 days post-infection, when no parasite or immune cell infiltration could be detected, the myocardium expressed high levels of NOS and NO metabolites. Nevertheless, the early production of NO in the myocardium was not sufficient to clear the parasites.
A novel point mutation in CD18 causing the expression of dysfunctional CD11/CD18 leucocyte integrins in a patient with leucocyte adhesion deficiency (LAD)
Authors: Mathew E C , Shaw J M , Bonilla F A , Law S K A , Wright D A 
Published: March 2003

SUMMARYLeucocyte adhesion deficiency type 1 (LAD-1) is characterized by the incapacity of leucocytes to carry out their adhesion functions via their CD11/CD18 antigens, which are also referred to as the leucocyte integrins. The patients generally suffer from poor wound healing and recurrent bacterial and fungal infections. In severe cases, the infections are often systemic and life-threatening. A LAD patient (AW) of moderate phenotype has been identified but, unlike most other cases, the level of CD11/CD18 antigens on her leucocytes are uncharacteristically high for a LAD patient. Molecular analysis revealed that she is a compound heterozygote for CD18 mutations. She has inherited a D231H mutation from her father and a G284S mutation from her mother. By transfection studies, it was established that the G284S mutation does not support CD11/CD18 antigen expression on the cell surface. In contrast, the D231H mutation does not affect CD18 forming integrin heterodimers with the CD11 antigens on the cell surface. However, the expressed integrins with the D231H mutation are not adhesive to ligands.
Soluble CD30 is more relevant to disease activity of atopic dermatitis than soluble CD26
Authors: Katoh N , Hirano S , Suehiro M , Ikenaga K , Yamashita T , Sugawara N , Yasuno H 
Published: March 2003

SUMMARYIt is suggested that CD30 and CD26 are surface molecules expressed on activated Th2 and Th1 cells, respectively. We examined plasma levels of soluble CD26 (sCD26) and sCD30 in patients with atopic dermatitis (AD) when their eruptions were aggravated and in non-atopic healthy controls, and then analysed the possible correlation between these values and the levels of several clinical markers. The plasma levels of both sCD30 and sCD26 were significantly higher in AD patients than in controls, both in exacerbation status and after conventional treatment. Multiple regression analyses showed that plasma sCD30 was a much better predictor of the levels of serum IgE, serum LDH and plasma sCD25, and the area and the score of AD eruption than sCD26, although elevated levels of both sCD30 and sCD26 are associated with these clinical predictors of AD. Importantly, sCD30 plasma levels decreased significantly in AD patients after conventional treatment, while no significant transition was noted in the concentration of sCD26. Moreover, a significant reduction of sCD30 levels was observed in the group of patients whose eruption score was reduced &gt; 50%, whereas it was not in those &lt; 50%. These findings provide evidence that the successful treatment of AD is associated with down-activation of Th2.
Role of caspases in dexamethasone-induced apoptosis and activation of c-Jun NH2-terminal kinase and p38 mitogen-activated protein kinase in human eosinophils
Authors: Zhang J P , Wong C K , Lam C W K 
Published: March 2003

SUMMARYEosinophils are the principal effector cells for the pathogenesis of allergic inflammation. Glucocorticoids such as dexamethasone have long been used therapeutically for eosinophilia in allergic inflammation by inducing eosinophil apoptosis, but little is known about the intracellular mechanisms mediating dexamethasone-induced apoptosis. In the present study, we investigated the effect of dexamethasone on three mitogen-activated protein kinases (MAPK) involved in the intracellular signalling pathway: c-Jun NH2-terminal kinase (JNK), p38 MAPK and extracellular signal-regulated kinase (ERK). We found that dexamethasone could activate JNK and p38 MAPK in a time-dependent manner but not ERK. Further, SB 203580, a specific p38 MAPK inhibitor, was additive with dexamethasone in inducing eosinophil apoptosis, while JNK1/2 antisense phosphorothioate oligodeoxynucleotides did not show any significant effect. These suggest that dexamethasone-induced JNK1/2 and p38 MAPK activation are not crucial to the induction of apoptosis. Pretreatment of eosinophils with benzyloxycarbonyl-Val-Ala-Asp-fluoromethylketone (Z-VAD.FMK), a broad-spectrum caspase inhibitor, could inhibit dexamethasone-induced apoptosis in eosinophils dose-dependently. Moreover, Z-VAD.FMK partially inhibited dexamethasone-activated JNK and p38 MAPK activities. However, dexamethasone treatment did not activate specific caspase-3, -8 activity in eosinophils compared with spontaneous apoptosis. We therefore conclude that dexamethasone-induced apoptosis and activation of JNK and p38 MAPK activity in eosinophils are regulated by caspases but not through the common apoptosis-related caspase-3, -8 as in other cell types. Elucidation of the important role of caspases in eosinophil apoptosis may facilitate the development of more specific and effective treatment for allergic inflammation.
Thep53status in juvenile chronic arthritis and rheumatoid arthritis
Authors: Taubert H , Thamm B , Meye A , Bartel F , Rost A-K , Heidenreich D , John V , Brandt J , Bache M , Würl P , Schmidt H , Riemann D 
Published: March 2003

SUMMARYThe aim of this study was to investigate the p53 status in two autoimmune diseases; juvenile chronic arthritis (JCA) and rheumatoid arthritis (RA). In a PCR-sequencing analysis of exons 4–9 of the p53 gene, no mutation was identified, except for the case of an RA synovectomy sample with two mutations of intron 7. p53 gene polymorphisms for codons 36, 47, and 213 were not detected. Codon 72 polymorphism showed an indication of an increased occurrence of the Pro/Pro allelotype in JCA. Expression of P53 protein was comparable for JCA and RA synovectomy samples. For all RA samples P53 protein was detectable, whereas one sample of a JCA patient failed to express P53 protein.
Effects of peroxisome proliferators on the thymus and spleen of mice
Authors: Yang Q , Xie Y , Depierre J W 
Published: March 2003

SUMMARY
The effects of peroxisome proliferators on the immune system of male C57Bl/6 mice have been investigated. Significant atrophy of the thymus and spleen was observed in animals treated with potent peroxisome proliferators (e.g. perfluorooctanoic acid (PFOA), di(2-ethylhexyl)phthalate (DEHP), Wy-14 643 and nafenopin), whereas the effects of a moderate peroxisome proliferator (i.e. acetylsalicylic acid (ASA)) were relatively weak. The time course of thymic and splenic atrophy caused by PFOA was found to resemble the time course of the increase in liver weight and of peroxisome proliferation. Analysis of the numbers and phenotypes of thymocytes and splenocytes from PFOA-treated mice revealed the following: (i) the numbers of thymocytes and splenocytes were decreased &gt; 90% and about 50%, respectively, by PFOA treatment; (ii) although all populations of thymocytes were decreased, the immature CD4+CD8+ population was decreased most dramatically; (iii) the numbers of both T and B cells in the spleen were decreased by PFOA treatment. Analysis of the cell cycle of thymocytes indicated that the thymic atrophy caused by PFOA in mice results, at least in part, from inhibition of thymocyte proliferation. Interestingly, in vitro exposure to PFOA for up to 24 h did not produce analogous effects in either thymocytes or splenocytes. Thus, the thymic and splenic atrophy caused by PFOA appears to involve an indirect pathway.
Characterization of the T cell recognition of hepatitis B surface antigen (HBsAg) by good and poor responders to hepatitis B vaccines
Authors: Desombere I , Gijbels Y , Verwulgen A , Leroux-Roels G 
Published: March 2003

SUMMARYTo study the regulation of the human cellular immune response to HBsAg we produced a series of HBsAg-specific T cell lines from good and poor responders to the hepatitis B vaccine. All T cell lines expressed CD4 on their membrane and could therefore be considered of the helper/inducer phenotype. The different HBsAg-specific T cell lines were restricted by HLA-DRB5*0101, DRB1*1201, -DRB1*0701, -DRB1*0301, -DPB1*0201, -DPB1*0402, and -DPB1*0901. In good responders to the hepatitis B vaccine different HLA molecules could act as restricting element. In poor responders the diversity of HLA class II restriction determinants was more limited. This leads us to conclude that the immune response to HBsAg is multispecific and polyclonal in good responders and paucispecific and oligoclonal in poor responders to the hepatitis B vaccine. By using a panel of synthetic peptides representing selected sequences of the HBsAg, the fine specificities of each of these T cell lines could be determined. Strikingly, the majority of the identified T cell epitopes was located in and around the first hydrophobic transmembranous region of the HBsAg. This was observed in T cell lines from good and poor vaccine responders, without distinction. The remarkable T cell immunogenicity of this region may reside in its richness in binding motifs for a variety of HLA class II determinants.
Parasite-mediated down-regulation of collagen-induced arthritis (CIA) in DA rats
Authors: Mattsson L , Larsson P , Erlandsson-Harris H , Klareskog L , Harris R A 
Published: March 2003

SUMMARYMicrobial infection can impact on the course of autoimmune disease, both in disease-inducing and disease-protecting capacities. Here we investigated if infection with Trypanosoma brucei brucei (Tbb), the protozoan causative agent of African Sleeping Sickness, could ameliorate the course of CIA in the Dark Agouti rat, an experimental model which shares many features with human rheumatoid arthritis. Infection of animals with living, but not inoculation with dead Tbb resulted in complete or significant reduction of clinical arthritic symptoms. Infection prior to collagen immunization was more effective than a later treatment, and this effect was related to the level of parasitaemia. Using reverse transcriptase-polymerase chain reaction we detected an increase in interferon-gamma mRNA in the draining lymph nodes of Tbb-treated animals relative to controls at day 28 after disease induction. Transforming growth factor-beta could be detected in the lymph nodes in four out of six animals that had received Tbb. In the joints, immunohistochemistry revealed reduced production of tumour necrosis factor-alpha in Tbb-treated animals relative to controls. The most striking difference between Tbb-infected and control groups, as measured by ELISA, was the down-regulation of anti-collagen II IgG antibody responses in parasite-infected animals. We conclude that live parasites can exert an immunomodulatory and protective effect in CIA in which several mechanisms may work in parallel, although the almost complete down-regulation of the anti-collagen antibody response may alone explain the protective effect in CIA. The described model may be useful in further attempts to use the mechanisms involved in parasite immune defence to prevent and treat certain autoimmune conditions.
T cell activation, apoptosis and cytokine dysregulation in the (co)pathogenesis of HIV and pulmonary tuberculosis (TB)
Authors: Hertoghe T , Wajja A , Ntambi L , Okwera A , Aziz M A , Hirsch C , Johnson J , Toossi Z , Mugerwa R , Mugyenyi P , Colebunders R , Ellner J , Vanham G 
Published: March 2003

SUMMARYImmune parameters were compared in four groups of Ugandan subjects: HIV−and HIV+ adult patients with active pulmonary TB (HIV− PTB n = 38; HIV+ PTB n = 28), patients with HIV infection only (n = 26) and PPD+ healthy controls (n = 25). Compared with healthy controls, CD4 and CD8 T cells from patients with HIV and/or PTB expressed more activation markers (HLA-DR, CD38); their CD8 T cells expressed more CD95 (pre-apoptosis) and less CD28 (co-stimulatory receptor). Peripheral blood mononuclear cells (PBMC) of patients with either HIV or PTB were impaired in interferon-gamma (IFN-γ) production upon antigenic stimulation. PTB (with or without HIV) was characterized by monocytosis, granulocytosis, increased transforming growth factor-beta 1 production and PPD-induced apoptosis. In vivo CD4 T cell depletion, in vitro increased spontaneous CD4 T cell apoptosis and defects in IFN-γ responses upon mitogenic stimulation were restricted to HIV+ subjects (with or without PTB). Overlapping and distinctive immune alterations, associated with PTB and HIV, might explain mutual unfavourable influences of both diseases.
Autoantibodies to early endosome antigen (EEA1) produce a staining pattern resembling cytoplasmic anti-neutrophil cytoplasmic antibodies (C-ANCA)
Authors: Selak S , Woodman R C , Fritzler M J 
Published: March 2003

SUMMARYAutoantibodies to EEA1 have been described in patients with neurological diseases, subacute cutaneous lupus and a variety of other conditions, including a patient with Wegener's granulomatosis (WG). EEA1 is a hydrophilic peripheral membrane protein transiently associated with the cytoplasmic face of early endosomes. Antibodies to EEA1 produce a staining pattern that resembles the C-ANCA pattern produced by anti-proteinase 3 (PR3) antibodies in WG sera. Co-localization studies show incomplete overlap of the staining produced by anti-EEA1 with anti-PR3. We showed that 0/40 unselected sera, from a cohort of WG patients and antibodies to PR3, reacted with EEA1. In addition, 1/15 sera that have a C-ANCA staining pattern but do not react with PR3 in an ELISA, immunoprecipitated the recombinant EEA1 protein. We conclude that although antibodies to EEA1 produce a staining pattern that resembles anti-PR3 and C-ANCA, antibodies to EEA1 in WG are rare. However, some C-ANCA+ sera that do not react with PR3 may contain EEA1 autoantibodies.