bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet surface IgG in patients receiving infusions of Fab fragments of a chimaeric monoclonal antibody to glycoprotein IIb-IIIa
Authors: CHRISTOPOULOS C 
Published: July 2010

SUMMARYPlatelet surface immunoglobulin G (PSIgG) was measured ex vivo in nine patients with stable angina pectoris receiving continuous (48–96 h) infusions of Fab fragments of a chimaeric MoAb (human IgG with murine variable regions) to platelet glycoprotein IIb-IIIa. PSIgG was measured using flow cytometry (FC) and an Fc-specific anti-IgG polyclonal antibody, which did not crossreact with the chimaeric Fab fragment (c7E3-Fab). A variable but statistically significant (P &lt; 0·05) elevation of PSIgG was present within 24 h after the onset of the infusion, and was more marked (P &lt; 0·01) several days after the end of the infusion despite an exponential fall in platelet surface c7E3-Fab post-infusion. PSIgG returned to normal within 2 weeks after the end of the infusion. The timing of IgG recruitment to the platelet surface suggested the pre-existence in the patients' plasma of IgG binding to c7E3-Fab-bearing platelets. None of the patients developed thrombocytopenia. In order to assess the incidence of IgG bindable to c7E3-Fab-bearing platelets in controls clinically comparable to the c7E3-Fab infusion patients, normal platelets coated with either chimaeric (c) or murine (m) 7E3-Fab were incubated with plasmas from 21 patients with ischaemic heart disease, and recruitment of IgG to the platelet surface was measured by FC. Fourteen of the 21 plasmas contained IgG bindable to c7E3-Fab-coated platelets, whereas only one of the 21 plasmas contained IgG bindable to m7E3-Fab-coated platelets (a highly significant difference, P &lt; 0 0·01). These findings indicate that Infusions of Fab fragments of the chimaeric anti-platelet antibody 7E3 are often associated with elevations in PSIgG, which are probably due to pre-existing “naturally occurring” antibodies to the Fab fragments of chimaeric (but not murine) 7E3, and most probably other chimaeric MoAbs. The possible clinical significance of such ex vivo measured activities is at present a matter for speculation, and requires further study.
HLA associations with inclusion body myositis
Authors: GARLEPP M J , LAING B , ZILKO P J , OLLIER W , MASTAGLIA F L 
Published: July 2010

SUMMARY
Inclusion body myositis (IBM) is defined clinically by a characteristic pattern of progressive proximal and distal limb muscle weakness and resistance to steroid therapy, and histologically by the presence of distinctive rimmed vacuoles and filamentous inclusions as well as a mononuclear infiltrate in which CD8+ T cells are predominant. Muscle damage is believed to be mediated by autoimmune mechanisms, but very little information is available on the immunogenic features of IBM. MHC class I and DR antigens were typed on 13 caucasoid patients with IBM using standard serological techniques or by allele-specific oligonucleotide typing. Complement components C4 and properdin factor B (Bf) were typed by immunofixation after electrophoresis. Restriction fragment length polymorphisms (RFLP) in the class ITT region were analysed using cDNA probes for C4 and 21-hydroxylase (CYP21) after Taq 1 digestion. IBM was associated with DR3 (92%), DR52 (100%) and HLA B8 (75%). The phenotype data were examined for likely haplotypes by considering together the alleles at the class T, DR and complement loci along with the C4 and CYP21 RFLP. Ten of the DR3+ subjects had a 6 4-kb C4-hybridizing fragment characteristic of a deletion of C4A and CYP21-A. These patients probably carried all, or at least the class II and III regions, of the extended haplotype marked by B8/C4A*Q0/C4Bl/BfS/DR3/DR52, which has been associated with several autoimmune diseases and is present in 11% of the healthy Caucasoid population. Of the remaining subjects, two had evidence of the extended haplotype marked by B]8/C4A3/C4BQ*0/BfFl/DR3, which is present in less than 5% of the healthy population and has been associated with insulin-dependent diabetes mellitus. These data provide support for an autoimmune etiology for, and genetic predisposition to, IBM.
Serologic markers of lupus nephritis in patients: use of a tissue-based ELISA and evidence for immunopathogenic heterogeneity
Authors: BERNSTEIN K A , KAHL L E , BALOW J E , LEFKOWITH J B 
Published: July 2010

SUMMARYIn order to assess the ability of various serologic assays to correlate with lupus nephritis, we analysed sera obtained from 60 patients with systemic lupus erythematosus (SLE), Patients were categorized as having active nephritis (group 1), active lupus without nephritis (group 2), inactive lupus with prior nephritis (group 3), or inactive lupus without prior nephritis (group 4), Three parameters were assessed including anti-dsDNA antibodies (Farr assay), immune complexes (C1q binding), and anti-C1q antibodies (salt-stable C1q binding). Additionally, glomerular binding activity (GBA) was measured using a new solid-phase immunoassay that detects immune elements by their ability to bind glomerular tissue. We found that patients with nephritis (group 1) exhibited higher mean values for each assay than patients in each of the other three groups (P= 0·001,0·009, 0·14, and 0·23 in the GBA, C1q, anti-dsDNA, and anti-C1q assays, respectively). The only assay which distinguished patients with nephritis (group 1) from patients having active disease without nephritis (group 2) was the GBA (mean 0·48 ± 0·09 versus 0·15 ± 0·04, (P 0·05), In terms of utility, all tests were specific for diagnosing nephritis among patients with lupus; however, only the GBA was reasonably sensitive. The information provided by the anti-dsDNA and C1q assays were not correlated with one another, nor additive to the GBA, Patients with false negative GBA tended to have received more intensive immunosuppression. The qualitative characteristics of GBA varied among patients with nephritis. These data suggest the pathogenesis of lupus nephritis is complex, and may be mediated by an array of immune elements. Moreover, the data indicate the potential utility for a broad tissue-based approach to detection of pathogenic immune elements over other, specific immunologic markers.
The development of transplant coronary artery disease after cardiac transplantation is correlated with a predominance of CD8+ T lymphocytes in endomyocardial biopsy derived T cell cultures
Authors: JUTTE N H P M , GROENEVELD K , BALK A H M M , OUWEHAND A J , LOONEN E H M , VAN DER LINDEN M , STRIKWERDA S , MOCHTAR B , CLAAS F H J , WEIMAR W 
Published: July 2010

SUMMARY
Long-term survival of heart transplant recipients is limited by the development of transplant coronary artery disease (TCAD). We analysed whether the development of TCAD is correlated with the incidence of acute rejection episodes, with the formation of anti-HLA antibodies or with the composition and function of T lymphocyte cultures derived from endomyocardial biopsies. TCAD was assessed by visual analysis of annually performed coronary angiograms and defined as the presence of all vascular changes, including minor wall irregularities. One year after transplantation, 31 of the 77 patients studied had TCAD (40%). The median age and mean number of HLA mismatches in patients with or without TCAD were highly comparable. The patient groups did not differ in incidence of acute rejection episodes, nor in percentage of endomyocardial biopsies yielding T cell cultures. At 1 year after transplantation, lymphocyte cultures from 18/31 TCAD+ patients (58%) and 27/46 TCAD- patients (57%) were analysed. The TCAD+ patients had, compared with the TCAD- patients, a higher median percentage of CD8+ T cells (71%versus 25%, P= 0·06) and a lower median percentage of CD4+ T cells (4%versus 40%, P= 0·04). Similar differences were found in a longitudinal analysis of the culture results of endomyocardial biopsies (EMBs) obtained during the first year. The cytotoxic reactivity of the cultures against donor HLA class I or class II antigens was comparable in the two groups, although a difference in recognition of heart specific antigens remains possible. The fact that EMB-derived cultures from TCAD+ and TCAD- patients differed in T cell phenotype populations gives some support to the hypothesis that cellular immunological processes are involved in the development of TCAD. However, while the median values differed, the overlap of the percentages of CD8+ cells in cultures from TCAD- and TCAD+ patients shows that other factors besides CD8+ T cells also play a role.
Progressive increase of CD7- T cells in human blood lymphocytes with ageing
Authors: KUKEL S , REINHOLD U , OLTERMANN I , KREYSEL H-W 
Published: July 2010

SUMMARYCD7 is one of the major surface antigens expressed very early during T cell ontogeny. Lack of CD7 expression on mature T cells is regarded as a classical feature of malignant T cells in certain forms of cutaneous T cell lymphoma. Previously, we identified a CD7- subset of peripheral blood T lymphocytes in normal human individuals. In this study we determined the portion of CD7- T cells in the peripheral blood of healthy volunteers ranging in age from 8 months to 90 years (n= 85) and in cord blood of full-term infants (n= 14), Furthermore, this CD7- subset was characterized in detail by the use of MoAbs and three-colour flow cytometry. In cord blood no CD7- T cells could be detected. After birth, percentage and absolute number of CD7- T cells increased with age. Independently of age, most CD7- CD3+ cells belonged to the CD4+ subpopulation. Focusing on the latter we could demonstrate the predominance of the CD45RO+CD45RA- phenotype in the CD7- subset. Furthermore, CD7- T cells contained a higher number of cells expressing activation markers and the CD57 antigen, but a reduced number of CD62L+ cells in comparison with CD7+ T cells.
Recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) or tumour necrosis factor-alpha (TNF-α) activate human alveolar macrophages to inhibit growth ofMycobacterium aviumcomplex
Authors: SUZUKI K , LEE W J , HASHIMOTO T , TANAKA E , MURAYAMA T , AMITANI R , YAMAMOTO K , KUZE F 
Published: July 2010

SUMMARYWe investigated the effects of certain macrophage-active cytokines on the phagocytosis and growth inibition of Mycobacterium avium complex (MAC) by human alveolar macrophages (AM). We also evaluated the effects of pretreatment with each cytokine on the superoxide anion release (O2-) from AM. The cytokines that we used were recombinant GM-CSF, natural type TNF-α, recombinant interferon-gamma (IFN-γ). and recombinant IL-2, We found that phagocytosis by the various cytokine-stimulated AM was similar lo that of unstimulated AM. On the other hand, significant growth inhibition of MAC was observed in the macrophages treated with GM-CSF or TNF-α, while no growth inhibition of MAC was observed in the macrophages treated with IF'N-γ or IL-2. Pretreatment with alt cytokines tested enhanced the O2- release from AM. but there was no correlation between the enhancement of O2- release and the growth inhibition of MAC, Thus, we concluded that GM-CSF or TNF-α could activate AM to inhibit growth of MAC, probably not through the enhanced production of reactive oxygen intermediates.
Treatment of anti-neutrophil cytoplasmic antibody (ANCA)-associated systemic vasculitis with high-dose intravenous immunoglobulin
Authors: RICHTER C , SCHNABEL A , CSERNOK E , DE GROOT K , REINHOLD-KELLER E , GROSS W L 
Published: July 2010

SUMMARY
In this uncontrolled study 15 patients with ANCA-associated systemic vasculitis, who were poor responders to conventional therapy, were treated with single or multiple courses of intravenous immunoglobulin (IVIG), 30g/day over 5 days. Clinical and serological evaluation was performed before and 4 weeks after IVIG. Six of the 15 patients experienced clinically significant benefit from IVIG. Improvement was confined to single organ manifestations (skin, ENT findings), no improvement was seen with conjunctivitis and scleritis, pericarditis or nephritis. No patient experienced complete remission after IVIG. Repeated courses of IVIG at 4-week intervals were no more effective than single courses. In six anti-proteinase 3 (PR3)-positive patients pretreatment sera were incubated with F(ab′)2 fragments of the IVIG preparation in vitro to measure the inhibitory effect of IVIG on anti-PR3 activity. An inhibition of anti-PR3 activity by 25–70% was observed; this did not correlate with clinical effects. Approximately 40% of patients benefited from IVIG treatment, though complete remission of disease activity did not occur. Neither clinical characteristics nor the inhibitory effect of the IVIG preparation on serum anti-PR3 activity in vitro predicted clinical response to this treatment modality.
Human autoantibodies directed against the RNA recognition motif of La (SS-B) bind to a conformational epitope present on the intact La (SS-B)/Ro (SS-A) ribonucleoprotein particle
Authors: RISCHMUELLER M , McNEILAGE L J , McCLUSKEY J , GORDON T 
Published: July 2010

SUMMARYIn systemic autoimmunity, the human B cell response to the La (SS-B) autoantigen is polyclonal and directed to both conserved and human-specific epitopes. This study has further characterized the B cell epitope(s) present within the conserved central region of the La protein, LaC (amino acids 111–242) containing the RNA recognition motif (RRM, aa 111–187). Ten overlapping and non-overlapping protein fragments spanning LaC were expressed in bacteria as NH2-terminal fusions with glutathione-S-transferase. The fusion proteins were tested by ELISA for reactivity with a panel of human anti-La sera in order to define the nature of the epitopes. Ninety-two percent of patient sera containing anti-La antibodies reacted with the region of La containing the RRM. Fine mapping of this reactivity using deletion mutants indicated that the deletion of 19 amino acids from either the NH2-terminal or COOH-terminal region of the RRM was associated with loss of antibody reactivity, suggesting that the immunodominant epitope expressed in this region is discontinuous. Autoantibodies affinity-purified from the La RRM fragment to remove other specificities immunoprecipitated newly synthesized native La (SS-B)/Ro (SS-A) complexes, providing additional evidence that autoantibodies were recognizing a conformational epitope. The findings indicate that the human autoantibody response to La involves recognition of a conformational determinant involving the conserved RRM region without necessarily interfering with the RNA-dependent association of the La/Ro ribonucleoprotein.
Characterization of murine monoclonal antibodies against 60-kD Ro/SS-A and La/SS-B autoantigens
Authors: VELDHOVEN C H A , PRUIJN G J M , MEILOF J F , THIJSSEN J P H , VAN DER KEMP A W C M , VAN VENROOIJ W J , SMEENK R J T 
Published: July 2010

SUMMARYSmall cytoplasmic ribonucleoproteins (scRNPs) are important autoantigens in patients with systemic lupus erythematosus and Sjögren's syndrome. MoAbs against these proteins were made by immunization of BALB/c mice with purified human recombinant 60-kD Ro/SS-A or 50-kD La/SS-B proteins. Five stable hybridoma cell lines were obtained, of which four secreted anti-Ro/SS-A antibodies (clones 1D8, 1D11, 2G10 and 6G8) and one produced anti-La/SS-B antibodies (clone 7F6). The MoAbs were further characterized using four different immunoassays: immunofluorescence, immunoblotting, RNA precipitation combined with Northern blotting, and recombinant protein precipitation. All lour MoAbs against Ro/SS-A recognized the native protein and one of them (2G10) recognized also intact scRNP particles. Interestingly, hY3-RNA was reproducibly not efficiently precipitated by MoAb 2G10. Epitope mapping using deletion mutants of the 60-kD Ro/SS-A antigen showed that MoAb ID8 recognized the C-terminal part of this protein, while 1D11 and 2G10 recognized distinct epitopes in the region between the RNP motif and the putative zinc finger domain. The epitopes recognized by these MoAbs lire highly conserved among species, and the epitope recognized by MoAb 2G10 may be identical to an autoepitope recognized by sera of patients. This is the first report describing the isolation and characterization of MoAbs of the IgG class against the 60-kD Ro/SS-A and La/SS-B autoantigens obtained by immunization with purified human recombinant proteins. These MoAbs can be of great use in studying the cellular processes in which scRNPs are involved, and may help to determine why these scRNPs become autoantigenic in autoimmune diseases.
Identification of HIV protein-derived cytotoxic T lymphocyte (CTL) epitopes for their possible use as synthetic vaccine
Authors: BRANDER C , PICHLER W J , CORRADIN G 
Published: July 2010

SUMMARYCTL are by far the most important defence mechanisms against viral infections, and many attempts have been undertaken to induce protective CTL in vivo. In order to identify CTL epitopes for their possible use as peptide-vaccine candidates, HIV proteins were screened for peptide sequences which (i) fulfil the binding motif of the HLA-A2.1 molecule, and (ii) are involved in the natural immune response to HIV. From 73 nonameric peptides satisfying the binding motif, 20 peptides were synthesized and their binding to HLA-A2.1 was monitored by measuring the expression of HLA-A2.1 molecules on the cell surface of the mutant cell line T2. To evaluate the involvement in natural HIV infection, strongly binding peptides were used in cytotoxicity assays to assess their capacity to generate a peptide-specific CTL response in vitro. From 20 nonameric peptides synthesized, only five showed strong binding to HLA-A2.1. All five binding peptides had the secondary anchor residues, recently proposed by Ruppert et al. [1] to be required for binding to HLA-A2.1. The discrimination between bound and unbound peptides confirmed the importance of these secondary anchor residues which, beside the known binding motif, may dictate if a peptide can bind to HLA-A2.1 or not. In HIV− donors, no CTL activity against any of the HIV-derived peptides was detectable after a 12-day in vitro stimulation. In contrast, HIV-infected persons showed a cytotoxic response against peptide-labelled target cells, suggesting that they had developed upon HIV infection a cytotoxic immune response against the identified CTL epitopes.
Adhesion molecules intercellular adhesion molecule-1 (ICAM-1), ICAM-3 and B7 are not expressed by epithelium in normal or inflamed colon
Authors: BLOOM S , SIMMONS D , JEWELL D P 
Published: July 2010

SUMMARYAdhesion molecules are involved in facilitating cell-mediated immune events. Because lymphocyte-epithelial cell interaction has been implicated in the pathogenesis of colonic inflammation, we analysed expression of a range of adhesion molecules on colonic epithelium in vitro and in vivo using flow cytometry, immunohistochemistry and in situ hybridization. Expression of ICAM-1 by cell lines HT29 and int407 was increased by proinflammatory cytokines interferon-gamma (IFN-γ), tumour necrosis factor-alpha (TNF-α) and IL-1 but not by IL-6. Vascular cell adhesion molecule (VCAM) and E-selectin were not expressed. Immunohistochemistry using sections of inflamed colon from 16 patients with ulcerative colitis (UC), five patients with Crohn's disease (CD) and seven patients with normal colonoscopic biopsies, showed no expression of ICAM-1 on colonic epithelium. VCAM was seen in isolated lymphoid aggregates and E-selectin was expressed on endothelium. In situ hybridization showed no ICAM-1 or ICAM-3 mRNA in colonic epithelium. B7, the ligand for CD28, was not found on normal or inflamed colonic epithelium. The adhesion molecules ICAM-1, ICAM-3 and B7 are not involved in lymphocyte–epithelial cell interaction in the normal or inflamed colon. This may have implications for the development of T cell tolerance to intestinal luminal antigens.
Neutrophil adhesion molecules in term and premature infants: normal or enhanced leucocyte integrins but defective L-selectin expression and shedding
Authors: REBUCK N , GIBSON A , FINN A 
Published: July 2010

SUMMARYThe functional deficits of neonatal neutrophils are well documented and are thought to contribute to the increased susceptibility of newborn infants to infection. We measured the adhesion molecules L-selectin. CDlla/CD18 and CDltb/CDI8 on neutrophils from the cord blood of term (n= 22) and premature (n= 32) infants using a whole blood method with flow cytometry and quantitative bead standards to enumerate cell surface receptors. We also assayed plasma for the shed form of L-selectin (sL-selectin). Our results suggested that L-selectin expression on term infant neutrophils is lower than that on adult neutrophils (unstimulated and stimulated, both P &lt; 0·001). but that stimulated premature infant cells express higher L-selectin than term infants (P &lt; 0·05); it is possible that this deficiency is caused by physiological changes occurring around the normal time of parturition. We observed reduced sL-selectin in term infants (P &lt; 0·001) compared with adults, and even lower eoncentrations in premature infants (P &lt; O−001). The sL-selectin concentrations in plasma may be a refiection of granulopoiesis, which may be reduced in premature infants. Our results showed increased resting neonatal neutrophil expression of CD11b/ CD 18 compared with adults, and the absence of any neonatal deficit of the ability to up-regulate CD11b/CD18 expression on stimulation. These findings are contrary to previous reports. Further studies suggested that the isolation procedures used in previous reports reduces the capability of the cells to respond to a formyl methionine leucine phenylalanine (fMLP) stimulus. This effect is more marked in neonatal neutrophils, suggesting that the previously reported deficiency is in fact due to the isolation techniques used rather than the cells’ innate ability to up-regulale CD11b/ CDI8 expression. The results of our study lead us to propose that the adhesive function of neonatal neutrophils may be less defective than previously thought.
T cell receptor repertoire in the peripheral blood and intestinal mucosa of coeliac patients
Authors: Lahat N , Ben-Nun A , Cohen L , Kinarty A , Lerner A 
Published: July 2010

SUMMARY
The αβ and γδ T cell receptor (TCR) repertoire in the peripheral blood and intestinal mucosa of six coeliac children and six age-matched controls was analysed by reverse transcription and polymerase chain reaction (PCR). No TCR αβ and γδ restriction was observed in coeliacs and controls. However, Vγ3 was expressed only in coeliac peripheral and intestinal T cells. Vδ2 was strongly expressed in coeliacs and scarcely transcribed in control cells. The unique expression of these γδ TCR in coeliac patients suggests that Vγ3 and perhaps Vδ2 TCR-bearing lymphocytes may play a role in the pathogenesis of coeliac disease.