bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impaired tumour necrosis factor-α (TNF-α) production and abnormal B cell response to TNF-α in patients with systemic lupus erythematosus (SLE)
Authors: MITAMURA K , KANG H , TOMITA Y , HASHIMOTO H , SAWADA S , HORIE T 
Published: July 2010

SUMMARYWe examined the TNF-α activity in culture supernatants of monocytes isolated from the peripheral blood of patients with SLE and of normal individuals. The monocytes from patients with SLE stimulated with silica particles, lipopolysaccharide or Staphylococcus aureus Cowan I secreted significantly lower amounts of TNF-α than did normal monocytes. A decreased TNF mRNA expression was observed in peripheral blood mononuclear cells stimulated by mitogens from patients with SLE. Furthermore, we examined the effect of recombinant TNF-α (rTNF-α) on the B cell function in SLE patients. rTNF-α inhibited the spontaneous Bcell proliferation of SLE, but tended to enhance the normal Bcell proliferation. Spontaneous IgM production from SLE Bcells was inhibited by rTNF-α, but that from normal B cells was not. Spontaneous IgG production was unaffected by rTNF-α. Also, rTNF-α did not affect the viability of B cells. These findings suggest that an impaired TNF-α production and an abnormal B cell response to TNF-α play a role in the immunological dysfunction in patients with SLE.
Tumour necrosis factor/cachectin plays a key role in autoimmune pulmonary inflammation in lupus-prone mice
Authors: DEGUCHI Y , KISHIMOTO S 
Published: July 2010

SUMMARYThe role of tumour necrosis factor-alpha (TNF-α) in the development of autoimmune pulmonary inflammation has been investigated in lupus-prone mice. An increase in TNF-α mRNA level from whole lung preparation of lupus-prone mice was evident, from 3 weeks to 12 weeks during growing process, as shown by Northern blot analysis, but not in control mice. Furthermore, it is also found that the major source of this increase in TNF-α mRNA was attributed to infiltrating mononuclear cells found within the lung. Treatment of lupus-prone mice with rabbit anti-mouse TNF-α IgG prevented the development of pulmonary inflammation lesions such as lung fibrosis and alveolitis. These results suggest that an increased TNF-α production by infiltrating mononuclear cells in the lungs of lupus-prone mice may play a role in the development of autoimmune pulmonary inflammation and in significant changes of cytokines and the immune responses in pulmonary inflammation lesions of lupus-prone mice.
Estimation of amounts of anti-La(SS-B) antibody directed against immunodominant epitopes of the La(SS-B) autoantigen
Authors: GORDON T P , GREER M , REYNOLDS P , GUIDOLIN A , MCNEILAGE L J 
Published: July 2010

SUMMARYThe contribution of circulating anti-La(SS-B) antibody to the hypergammaglobulinaemia seen in primary Sjögren’s syndrome is unknown. In this study levels of anti-La(SS-B) antibody directed against three immunodominant epitopes of the anti-La(SS-B) autoantigen were measured by ELISA in 84 anti-La(SS-B)+ sera using purified recombinant protein and antibody affinity-purified against the three anti-La(SS-B) fusion proteins. There was marked variation in the amounts of IgG anti-La(SS-B) antibody detected, with levels ranging from 0.02 mg/ml to 11 mg/mt. The anti-La(SS-B) levels were &gt; 1 mg/ml in 61% of patients; in 18% of sera the anti-La(SS-B) level constituted 10% or more of the total serum IgG. However, other patients were seen with marked hypergammaglobulinaemia and low anti-La(SS-B) concentrations. These results support an antigen-driven mechanism for the anti-La(SS-B) response and suggest that anti-La(SS-B) antibody production is regulated independently of other immunoglobulins.
Anti-IL-lα autoantibodies in patients with rheumatic diseases and in healthy subjects
Authors: SUZUKI H , AYABE T , KAMIMURA J , KASHIWAGI H 
Published: July 2010

SUMMARYWe have developed a quantitative assay for IgG autoantibodies against IL-lα using protein A-Sepharose CL-4B. We examined the autoantibodies in sera from 107 healthy subjects, 151 patients with rheumatoid arthritis (RA), 64 patients with systemic lupus erythematosus (SLE) and 16 patients with systemic sclerosis. The frequency of positive sera for the autoantibodies in patients with RA was 16.6%, which was about three times more frequent (P&lt;0.01) than that in healthy subjects (5.6%) or that in patients with SLE (4.7%). Only one serum of 16 patients with systemic sclerosis was positive for the autoantibodies. Neutralizing activity of the autoantibodies was demonstrated by murine thymocyte proliferation assay. The concentrations of IgG at 50% inhibition of IL-lα (15 pM) induced thymocyte proliferation ranged between 0.1 and 0.5 mg/ml. A time-course study showed fluctuations of the titres of the autoantibodies in parallel with the disease activity of RA. These results suggest that the anti-IL- lα autoantibodies present in the sera and possibly some other body fluids may be involved in the regulation of IL-1 activity in rivo.
Impaired T cell signal transduction through CD28 in a patient with idiopathic thrombocytopenia
Authors: PÉREZ-BLAS M , ARNAIZ-VILLENA A , GÓNGORA R , SEGURADO O G , VIVANCO J L , REGUEIRO J R 
Published: July 2010

SUMMARYWe describe an infant whose peripheral blood mononuclear cells were unable to proliferate or synthesize IL-2 in response to a mitogenic combination of antibodies directed against CD2 and CD28. This peculiar defect, which has been stable to dale, was attributed to an impairment in CD28-mediated T cell activation, because further comitogenic combinations containing anti-CD28 monoclonals also failed to induce normal proliferation of the patient’s T cells. In contrast, proliferation after membrane stimulation (with anti-CD2, recombinant IL-2, or certain lectins) or transmembrane activation (with phorbol ester and calcium ionophore) was normal, suggesting that his lymphocytes did not have a general membrane or intracellular signalling impairment. A T cell line derived from the patient confirmed the existence of a severe defect in CD28-mediatcd T cell proliferation, but also showed a profound impairment in CD3-induced T cell proliferation. Other cell surface molecules like CD2 and CD25 were, in contrast, capable of transducing normal proliferation signals. As all relevant molecules were detectable by cytofluorography and immunoprecipilalion, we conclude that the patient’s lymphocytes had an intrinsic defect in the delivery of CD28-mediated signals which, in the absence of monocytes, also affected CD3-mediated proliferation. The study of this novel kind of immunodeficiency may help to unravel the complex interactions that take place among CD2. CD3 and CD28 during T cell activation. The presence of an idiopathic thrombocytopenia in the patient suggests the intriguing possibility of a role for CD28 in the maintenance of peripheral blood platelets levels, although alternative interpretations are not ruled out.
Reduced frequency of nickel allergy upon oral nickel contact at an early age
Authors: VAN HOOGSTRATEN I M W , ANDERSEN K E , VON BLOMBERG B M E , BODEN D , BRUYNZEEL D P , BURROWS D , CAMARASA J G , DOOMS-GOOSSENS A , KRAAL G , LAHTI A , MENNE T , RYCROFT R J G , SHAW S , TODD D , VREEBURG K J J , WILKINSON J D , SCHEPER R J 
Published: July 2010

SUMMARYFrom animal studies we know that oral administration of T-dependent antigens before sensitization effectively induces systemic immune unresponsiveness. Such ‘oral tolerance’ is persistent, dose-dependent, antigen-specific and presumably T suppressor cell-mediated. Oral tolerance induction could be an effective way to prevent undesired T cell-mediated immune functions, such as playing a role in allograft reaction, autoimmune and allergic diseases. In the present study allergic contact hypersensitivity (ACH) to nickel, currently presenting the most frequent contact allergy in man, was chosen to establish the feasibility of oral prevention of undesired T cell-mediated immunity in man. Potentially tolerizing (oral nickel contacts via orthodontic braces) as well as sensitizing (ear piercing) events were studied retrospectively in 2176 patients attending nine European patch test clinics. Patients were interviewed by means of a confidential questionnaire. The results show that ear piercing strongly favoured development of nickel ACH. More importantly, patients having had oral contacts with nickel-releasing appliances (dental braces) at an early age, but only if prior to ear piercing, showed a reduced frequency of nickel hypersensitivity. Frequencies of other hypersensitivities, in particular to fragrance, were not affected. These results support our view that induction of specific systemic immunologic tolerance by timely oral administration of antigens is feasible in man.
Circulatory antigen of Heymann nephritis. III. Presence of the 70-kD circulatory protein in the immune deposits of Heymann nephritis
Authors: SINGH A K , SCHWARTZ M M 
Published: July 2010

SUMMARYAn antigen of 70 kD size has been isolated previously from normal rat serum which has immunological cross-reactivity to the Heymann nephritis antigen, F x 1 A. Its role in the pathogenesis of Heymann’s nephritis was unknown. In this investigation we tested for the presence of 70-kD circulatory antigen in the glomerular immune deposits of Heymann’s nephritis. Further, its presence was correlated with severity of disease. It was observed that the presence of the 70-kD antigen strongly correlated with the existence of electron-dense deposits in the lamina rara externa (LRE) of the glomerular capillary wall and with pathologic proteinuria. Temporally, the presence of the 70-kD antigen in the immune deposits was followed by large electron-dense deposits, enhanced complement activity and proteinuria. The data suggest that in the growing immune complex lattice in the LRE. the 70-kD circulatory antigen by virtue of its small size, mobility and antigen cross-reactivity facilitates cross linking and coalescence of immune complexes, resulting in electron-dense immune deposits (EDD) formation which initiates complement activation and consequent proteinuria.
Changes in phenotypically distinct mucosal macrophage populations may be a prerequisite for the development of inflammatory bowel disease
Authors: ALLISON M C , POULTER L W 
Published: July 2010

SUMMARYPrevious studies have demonslraled the presence of much more marked macrophage heterogeneity in colonic mucosa affected by the idiopathic inflammatory bowel diseases (ulcerative colitis and Crohn’s disease) than in normal mucosa. This study examines the morphology, distribution and phenotypic expression of mucosal macrophage-like cells in biopsies from patients with idiopathic inflammatory bowel disease in comparison with disease control samples from patients with colonic infection or ischaemia. Approximately 80% of macrophage-like cells in histologically normal mucosa co-express the antigens recognized by the monoclonal antibodies RFDI (an interdigitating cell marker) and RFD7 (a marker for mature tissue macrophages). In idiopathic inflammatory bowel disease, the normal colonic macrophage population is partly replaced by cells staining positively with RFD7 alone, and, to a lesser extent, with RFDI+ dendritic cells. Sections from patients with infections and ischaemia exhibited epithelial HLA-DR positivity and infiltration of the lamina propria by a more heterogeneous population of macrophages than that seen in histologically normal mucosa. However, the displacement of the normal colonic macrophage phenotype by RFD7+ tissue macrophages occurred to a significantly greater extent in idiopathic inflammatory bowel disease than in disease control mucosa. A pathognomonic feature of the ulcerative colitis and Crohn’s colitis sections was the clustering of RFD9+ epithelioid cells at the bases of disrupted crypts and adjacent to areas of mucosal damage. It is concluded that a degree of macrophage heterogeneity and macrophage infiltration can occur as a non-specific response to colonic mucosal damage. The distinctive feature of idiopathic inflammatory bowel disease mucosa is the almost complete replacement of the normal colonic mucosal macrophage population by tissue macrophages and epithelioid cells, and this phenomenon may be important in promoting the development of a chronic inflammatory state
Analysis of the molecular mimicry between HLA-B27 and a bacterialOmpAprotein using synthetic peptides
Authors: YU D T Y , HAMACHI T , HAMACHI M , TRIBBICK G 
Published: July 2010

SUMMARYIn spite of a lack of sequence ‘homology’ between HLA-B27 and the bacterial OmpA outer membrane proteins, they both react with the Ye-2 monoclonal anti-HLA-B27 antibody. The Ye-2 antibody also reacted positively in ELISA with a synthetic peptide derived from the segment spanning residues 63–84 of B*2705. The critical peptide residues were determined by testing first with overlapping peptides, followed by a replacement set made according to the determined epitope. The results were compared with those with overlapping eight mers made to span a carboxyl fragment of the Escherichia coli OmpA. protein. They indicate the reason why Ye-2 reacts with both sets of peptides is because it has a preference for polymers of arginine.
Murine and human B cell epitope mapping of the Mycobacterium tuberculosis 10-kD heat shock protein using overlapping peptides
Authors: VERBON A , HARTSKEERL R A , KOLK A H J 
Published: July 2010

SUMMARY
The human immune response to the 10-kD M. tuberculosis protein was studied by a competition ELISA using monoclonal antibody (MoAb)SA-12. Twenly-five per cent of the sera from 20 patients with tuberculosis and none from 21 control subjects inhibited binding of SA-12 to the 10-kD antigen. To characterize theantigenic parts of the 10-kD antigen, overlapping decapeptides according to the amino acid sequence of the 10-kD protein were synthesized. In total. 91 sequential decapeptides, with an overlap of nine amino acids, were tested in ELISA with MoAb SA-12, human and murine sera (PEP scan). SA-12 recognized the amino acid sequence WDEDGEK (amino acid 50 56). All human sera, from patients with tuberculosis as well as from control subjects, gave almost identical undulating patterns of reactivity with the decapeptides. No relationship was found between the ability of the patients’ sera to inhibit binding of MoAb SA-12 and the binding of these sera to the decapeptides comprising the epitope recognized by SA-12 in the PEP scan. Apparently, antibodies in patients’ sera against the 10-kD protein are predominantly directed against discontinuous epitopes and, consequently, the continuous epitopes as presented in the PEP scan are not suitable to discriminate between patients with tuberculosis and control subjects. In the PEP scan, sera from BALB/c mice, both non-immunized and immunized with either live M, tuberculosis or the 10-kD protein gave similar patterns of reactivity, albeit different from the patterns obtained with the human sera. However, after immunization of the mice, clearly increased levels of antibodies to primary structures of the 10-kD protein were observed.
Lymphocyte subpopulations in pyogranulomas of caseous lymphadenitis
Authors: WALKER J , JACKSON H , BRANDON M R , MEEUSEN E 
Published: July 2010

SUMMARYPyogranulomas of ovine caseous lymphadenitis (CLA) are encapsulated lesions resulting from infections with Corynebacterium pseudotuberculosis, a bacterial pathogen able to grow within macrophages. Immunohistology of CLA lesions showed a band of lymphocytes lining the inside of the collagen capsule in intimate contact with necrotic tissue, the intracapsular lymphocytes being organized into three layers. The innermost layer, immediately adjacent to the central necrotic tissue consisted of a narrow band of MHC class II staining macrophages. Cells staining for CD4. CD8 and γδ T cell markers were unevenly distributed throughout the lymphoid layer, tending to be more numerous immediately external to the macrophage layer. The intracapsular lymphoid tissue contained a high proportion of CD8+ lymphocytes (CD4:CD8, 1.5:1) and of γδ lymphocytes (CD4:CD8:γδ, 1:0.7:0.8). External to the T cell-rich zone and adjacent to the surrounding collagen capsule was a dense band of cells, a proportion of which stained atypically for CD45R and were tentatively identified as B cells. CDS+ and γδ+ T cells showed similar distributions and their relative abundance, compared with CD4+ T cells, was a distinguishing feature of the CLA lesion. Staining for factor VIII-related antigen clearly showed endothelial venules throughout the intracapsular lymphoid tissue. The presence of endolhelial vcnules and the organized architecture of the lymphoid tissue teleologically argues that lymphocytes are continually recruited into chronic CLA lesions and play an important role in the ongoing disease process.
Human cerebral malaria: characterization of malarial antibodies in cerebrospinal fluid
Authors: MITRA S , RAVINDRAN B , DAS B K , DAS R K , DAS P K , RATH R N 
Published: July 2010

SUMMARY
Anti-malarial antibodies were quantified in cerebrospinal fluid (CSF) of 17 cases of cerebral malaria, 16 presumptive cases (no demonstrable parasitaemia in peripheral blood but responding to i.v. quinine therapy) of cerebral malaria, and 15 controls. A schizont-enriched Plasmodium knowlesi antigen was used in an ELISA. Anti-malarial antibodies of IgA and IgM isotypes were not detectable in most of the CSF samples analysed, although serum antibody titres were high. However, 88% of CSF from cerebral malaria and 56% of presumptive cerebral malaria cases had significant levels of IgG anti-malarial antibodies in comparison to control CSF. The antibody levels did not correlate with the severity of coma but correlated well with the duration of coma. The CSF malarial antibody titres were independent of degree of parasitaemia. The possible role of CSF anti-malarial antibodies in cerebral malaria in the light of recent demonstrations of intrathecal synthesis of immunoglobulins and deposition of immune complex in cerebral tissues is discussed.
Cytotoxicity of human natural killer (NK) cell subsets forPlasmodium falciparumerythrocytic schizonts: stimulation by cytokines and inhibition by neomycin
Authors: ORAGO A S S , FACER C A 
Published: July 2010

SUMMARYQuantification of human peripheral blood NK subsets has been made in a group of Kenyan adults and children with acute P. falciparum malaria. Results were compared with data obtained from three age- and sex-matched control cohorts: parasitaemic but asymptomatic children: aparasitaemic children and adults; and adult Caucasians with no previous history of malaria. Separated NK subsets were tested in vitro for cytotoxicity to erythrocytic sehizonts of P. falciparum in the presence and absence of cytokines. There was a statistically significant quantitative and qualitative depression of the CD3- CD56+ subset in patients with acute malaria and this was accompanied by an expansion of the ‘non-functional’ CD3- CD57+ CD16- CD56- subset. Both CD3- CD16+ and CD3- CD56+ NK cells from all patients and donors lysed schizonts. and this cytotoxicity was enhanced by the addition of recombinant interferon-alpha and or IL-2, notably with the CD3- CD56+ subset. Interestingly, asymptomatic donors had the highest levels of CD3- CD56+ NK cells, which also demonstrated an enhanced response to cytokine stimulation. Cytotoxicity to schizonts was accompanied by the release of soluble NK cell lytic factors. Neomycin suppressed cytotoxicity in a dose-dependent manner, Indicating that the lysis of schizonts by NK cells involves phospholipase C-mcdiated phosphoinositide metabolism. Our findings define a role for NK cells in immunity to malaria through the lysis of infected erythrocytcs as a first-line defence against the parasite.
Mapping of epitopes on Ul snRNP polypeptide A with synthetic peptides and autoimmune sera
Authors: BARAKAT S , BRIAND J P , ABUAF N , VAN REGENMORTEL M H V , MULLER S 
Published: July 2010

SUMMARYThe ability of synthetic peptides encompassing almost the entire sequence of snRNP U1A polypeptide to be recognized in ELISA by sera of autoimmune patients was investigated. Sera from 18 patients with mixed connective tissue disease (MCTD), 145 with systemic lupus erythematosus (SLE) and 120 with other rheumatic autoimmune diseases were tested with 13 overlapping peptides. Among them, peptide 257–282 and, to a lower extent, peptide 1–11 were recognized by MCTD, SLE and Sjogren’s syndrome sera. In contrast, peptide 35–58 was recognized by 94% of MCTD and only 19% of SLE sera. It did not react with any of the other patient sera. The ELISA results were compared with the pattern of reactivity observed in immunoblotting. The results indicate that peptide 35–58 probably contains a major epitope recognized by MCTD autoantibodies. It is noteworthy that in snRNP particles, this region of U1A interacts with RNA and presents only limited homology with the corresponding sequence 32–50 of U2B”.
Detection and occurrence of the 60- and 52-kD Ro (SS-A) antigens and of autoantibodies against these proteins
Authors: SLOBBE R L , PRUIJN G J M , DAMEN W G M , VAN DER KEMP J W C M , VAN VENROOIJ W J 
Published: July 2010

SUMMARY
The simultaneous detection of anti-La. anti-60-kD Ro and anti-52-kD Ro antibodies by immunoblotting is greatly improved by changing the crosslinking level in the gel to an acrylamide/bisacrylamide ratio of 19:1. Using this method for the analysis of a number of systemic lupus erythematosus (SLE) and Sjögren’s syndrome patient sera it was observed that antibody to the 52-kD Ro protein without anti-60-kD Ro antibody was restricted to Sjogren’s syndrome patients (9/26), whereas antibody to the 60-kD Ro protein without contaminating anti-52-kD Ro antibody was only found in SLE patients (8/38). Moreover, in Sjogren’s sydrome patient sera anti-Ro antibody was found only in combination with anti-La antibody (20/26). whereas in SLE patient sera anti-Ro antibody could be found without detectable anti-La specificity (4/38). Double immunofluorescence microscopy revealed that the 52-kD Ro and the 60-kD Ro proteins co-localize in the cytoplasm as well as in the nucleus, whereas immunoprecipitation of [32P]-labelled HeLa cell extract with monospecific anti-52-kD Ro and anti-60-kD Ro sera showed that both proteins are associated with the Ro RNAs. These data suggest the presence of both the 52-kD and the 60-kD Ro proteins in the same ribonucleoprolein complexes. To study the evolutionary conservation of the 52-kD Ro, the 60-kD Ro and the La proteins, extracts of cell lines derived from various mammalian species were analysed on Western blols using monospecific human antibodies. In contrast to the 60-kD Ro and the La antigens which are well conserved in evolution, the 52-kD Ro antigen could be detected in primate cells only by this immunological approach.