bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cationic and high affinity serum IgG anti-dsDNA antibodies in active lupus nephritis
Authors: SUENAGA R , ABDOU N I 
Published: July 2010

SUMMARYTo investigate differences between cationic anti-dsDNA antibodies during active and inactive nephritis, low- and high-affinity IgG anti-dsDNA antibodies were prepared from sera of a lupus patient and compared for their binding affinity, spectrotype, and idiotype expression. The ratio of high-affinity to low-affinity anti-DNA antibodies and the relative avidity of the high-affinity anti-DNA antibodies decreased when active nephritis became inactive. Isoelectric focusing showed that cationic anti-dsDNA populations were present predominantly in the high-affinity fraction during active nephritis and in the low-affinity fraction during inactive nephritis. Idiolypic analysis by ELISA and Western blotting showed that the high-affinity cationic anti-DNA antibodies during active nephritis were idiotypically different from their low-affinity counterparts during inactive nephritis. The differences in binding affinity and idiotypy of the cationic anti-dsDNA antibodies suggest that certain serum IgG anti-dsDNA antibodies with both cationic charge and high affinity may be associated with active nephritis.
A calreticulin-like protein co-purifies with a ‘60 kD’ component of Ro/SSA, but is not recognized by antibodies in Sjögren's syndrome sera
Authors: LU J , WILLIS A C , SIM R B 
Published: July 2010

SUMMARYIn this study, we used human tonsils for the isolation of the 60 kD component of the Ro/SSA autoantigen. following the method described by Wu et al. (J Immunol Methods 1989; 121:219–24). Western blot analyses were carried out using Ro/SSA-reactive human Sjögren's syndrome sera, to follow the autoantigen through the purification procedure. A 60 kD Ro/SSA component was eluted as a broad peak from a Mono Q column. Within this peak, a much more abundant protein, comigrating with the Ro/SSA component on SDS-PAGE, was also eluted. The more abundant protein was further purified on a Superose 12 column and its N-terminal sequence was shown to be identical to that of humat calreticulin. The 60 kD Ro/SSA autoantigen was also further purified on the Superose 12 column and was eluted as an asymmetric peak, with the majority being eluted at a position corresponding to 60 kD, whereas the calreticulin-like protein was eluted from the same column as an apparent dimer of approximately 120kD. A panel of five Ro/SSA-reactive human sera reacted with the purified Ro/SSA antigen, but not with the calreticulin-like protein. Therefore, it is clear that the calreticulin-like protein is not a Ro autoantigen and is distinct from the 60 kD Ro/SSA antigen. As the calreticulin-like protein is a much more abtitidant protein than the 60 kD Ro/SSA component, its co-purification with the autoantigen on ion-exchange and its close migration with the autoantigen on SDS-PAGE may explain why peptide sequences for human calreticulin were derived from apparent 60 kD Ro/SSA antigen preparations.
Induction of an anti-Fab, anti-DNA and anti-RNA polymerase I autoantibody response net work in rabbits immunized with SLE anti-DNA antibody
Authors: ROMBACH E , STETLER D A , BROWN J C 
Published: July 2010

SUMMARYSystemic lupus erythematosus (SLE)-like anti-IgG Fab autoantibodies (autoAb) were induced in rabbits by immunization with either human, mouse or rabbit anti-DNA Ab. In direct-binding radioimmunoassay (RIA), affinity-purified anti-normal rabbit (NR) Fab autoAb cross-reacted with normal mouse (NM) Fab, ssDNA (but not dsDNA), poly(dA,dT), and RNA polymerase I (RPI). Affinity-purified anti-NM IgG Ab isolated from the same antisera cross-reacted with NR Fab, ssDNA and RPI. In inhibition RIA, soluble NR Fab inhibited anti-NR Fab binding to NR Fab and ssDNA, but enhanced binding to RPI. In contrast, ssDNA or RPI inhibitors had no effect upon autoAb binding to NR Fab. Anti-DNA, anti-RPI and anti-RPI 190 kD subunit autoAb, induced by immunization with lupus mouse anti-DNA Ab, also reacted with NM Fab, but were idiotypically specific for lupus mouse anti-DNA Fab. Further, rabbit anti-DNA and anti-RPI IgG autoAb, induced by immunization with rabbit anti-DNA IgG, were each idiotypically specific for homologous and autologous rabbit anti-ssDNA Fab. Together, these data provide evidence that anti-DNA, anti-RPI and anti-Fab autoAb are linked in a complex, multiple-specific and perhaps regulatory, immune response idiotype network in SLE.
Intercellular adhesion molecule-1 (ICAM-1) in Graves' disease: contrast betweenin vivoandin vitroresults
Authors: CIAMPOLILLO A , NAPOLITANO G , MIRAKIAN R , MIYASAKI A , GIORGINO R , BOTTAZZO G F 
Published: July 2010

SUMMARYWe have reassessed the possible role of the adhesion molecule ICAM-l in the pathogenesis of thyroid autoimmunity. In order to do that, we have investigated its expression in eight Graves' thyroids both in vivo (i.e. on cryostat sections and on cell suspensions), and in vitro (i.e. on cells cultured in monolayers for 3 days), and the results were compared with those obtained with similar preparations from four normal glands. On cryostat sections, the expression of ICAM-1, and for comparison that of HLA Class I and Class II molecules, was studied by immunofluorescence (IFL), but the former were also assessed by a distinct immunohistochemical technique. ICAM-1 was not detected in thyrocytes in vivo of both normal and Graves' glands, but solely in endothelial cells and antigen-presenting cells (APC). This selective reaction was confirmed by a four-layer technique using specific markers which identify endothelial cells and thyrocytes. HLA Class II molecules were confirmed to be inappropriately expressed in thyrocytes of Graves' glands, but there was no co-expression of these products and ICAM-1 in the same cells. In contrast, ICAM-1 appeared de novo in a proportion of Graves' and normal thyrocytes soon after the attachment and spreading of these cells in monolayer cultures (36–48 h). Graves' thyrocytes showed a quantitively higher degree of expression compared with that detected on normal thyroid cells (40–70%versus 12–20%). Under these experimental conditions, the four-layer staining with thyroid microsomal antibodies confirmed that thyrocytes were indeed the positive cells which expressed ICAM-l. Blocking experiments with cultured thyrocytes from two Graves' glands and MoAbs to tumour necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) did not prevent the occurrence of ICAM-l expression. As a result of our study, we failed to demonstrate that Graves' thyrocytes express ICAM-1 in vivo. The unexpected ease of inducing ICAM-1 on thyroid cells under certain in vitro conditions remains intriguing. The phenomenon could be the simple consequence of a mechanical effect rather than exerted by specific biological processes. Further investigations are, therefore, needed to establish whether lCAM-1 is really involved in the pathogenesis of Graves' disease.
Natural and acquired resistance toLeishmania: cellular activation byLeishmania aethiopicaof mononuclear cells from unexposed individuals is through the stimulation of natural killer (NK) cells
Authors: AKUFFO H , MAASHO K , HOWE R 
Published: July 2010

SUMMARYCells from normal non-Leishmania-exposed individuals could respond in vitro by proliferation and interferon-gamma (IFN-γ) production to Leishmania aethiopica stimulation. The main cell type that appeared to be activated following such stimulation was CD3−, CD16+/56+. i.e. NK cells. Of the few CD3+ cells responding, an involvement of CD8+ cells was evident in the absence of activation of CD4+ cells in normal individuals, while a different feature was observed when patients' cells were investigated. Cells from patients with L. aethiopica infection did not show this NK response, but rather the CD4+ cells were the prominent responding cells. No evidence of the involvement of superantigens or cells utilizing the γδ T cell receptor (γδcells) in the response of unexposed individuals was noted.
Anticardiolipin antibodies in HIV infection: association with cerebral perfusion defects as detected by 99mTc-HMPAO SPECT
Authors: RUBBERT A , BOCK E , SCHWAB J , MARIENHAGEN J , NÜBLEIN H , WOLF F , KALDEN J R 
Published: July 2010

SUMMARY
Anticardiolipin antibodies (ACA) belong to a heterogeneous group of antibodies directed against negatively charged phospholipids. In patients with rheumatic disorders, their presence has been correlated to the occurrence of thromboembolic complications, thrombocytopenia, abortions and other disease manifestations. Several studies have revealed the detection of mostly high-titre ACA in a significant proportion of HIV-infected patients without any known clinical relationship. In our study, ACA were detected in 17/34 HIV-infected patients, and their presence was significantly associated with the detection of cerebral perfusion abnormalities by 99mTc-HMPAO SPECT. SPECT scans were classified as normal or as focal or diffuse defects in uptake. Most patients (13/16) with cerebral perfusion defects had elevated ACA titres in contrast to 4/18 patients with normal SPECT findings (P= 0·002). Focal uptake defects were always associated with the presence of ACA. No correlation to clinical features or other laboratory parameters was evident. Our results suggest a possible implication of autoimmune mechanisms in the pathogenesis of cerebral perfusion abnormalities detected by SPECT scanning in HIV-infected patients. However, further studies are needed to evaluate the clinical significance and to develop possible therapeutic consequences.
Tryptic peptides of human thyroglobulin: I. Immunoreactivity with murine monoclonal antibodies
Authors: SABOORI A M , BUREK C L , ROSE N R , BRESLER H S , TALOR M , KUPPERS R C 
Published: July 2010

SUMMARYHuman thyroglobulin (Tg) was treated with trypsin at different concentrations of trypsin/Tg for various incubation times at 37°C using non-reducing conditions. A ratio of trypsin to Tg of 1:100 (w/w) was optimal to release small peptides that were reactive to murine MoAbs to human Tg. Most peptides were released after only 1 h incubation with trypsin, but these peptides were further degraded at longer incubation times. However, a few small peptides. the largest of which with an apparent molecular weight (MWap) of 40kD, resisted tryptic digestion up to at least 12 h of incubation. These resistant peptides were further degraded by trypsin at 18–24 h of incubation. Tryptic peptides of Tg, released at I h and 4 h of incubation, were analysed for their immunoreactivity to 16 well characterized anti-Tg MoAbs by Western immunoblot. Patterns of peptide recognition of these MoAbs were generally unique. Eight MoAbs reacted with peptides of MWapof 10–25 kD and above. Four other MoAbs reacted with peptides of MWap of 25 43 kD and above, and the remaining four reacted with peptides of MWap &gt;43kD. Nine of these MoAbs failed to recognize peptides after reduction, suggesting that the MoAbs bind conformation-dependent epitopes. The above information will promote the development of models relating the structure of Tg to the autoimmune process, and may provide an understanding of those regions of Tg responsible for the induction of autoimmune thyroiditis.
IgG subclass distribution of thyroglobulin antibodies in patients with thyroid disease
Authors: CATUREGLI P , KUPPERS R C , MARIOTTI S , BUREK C LVNNE , PINCHERA A , LADENSON P W , ROSE N R 
Published: July 2010

SUMMARYThe IgG subclass distribution of thyroglobulin antibodies (TgAb) has been studied in Hashimoto and Graves’ patients by several investigators with conflicting results, in part explainable by methodological problems. We have recently developed a quantitative ELISA to measure in absolute terms the serum concentration of TgAb subclasses. The aim of the present study was to apply this method in a large series of patients with autoimmune as well as, for the first time, non-autoimmune thyroid diseases. We examined 28 patients with Hashimoto's thyroiditis, 30 with Graves’ disease, 21 with thyroid carcinoma and 18 with non-toxic goitre, all selected for the presence of TgAbs. The results indicated that TgAbs in thyroid diseases were not restricted to any particular isotype, but comprised all four IgG subclasses. IgG1 was represented similarly in the four groups. The same was true for IgG3, even though its contribution to the total antibody content was very small. IgG4 was the dominant subclass in patients with Graves’ disease, thyroid carcinoma and non-toxic goitre, probably reflecting a prolonged antigenic challenge. In Hashimoto's thyroiditis IgG2 was dominant, possibly because T helper lymphocytes infiltrating the thyroid are typically Th1 type.
Expansion of CD3+CD4−CD8− T cell population expressing high levels of IL-5 in Omenn's syndrome
Authors: MELAMED I , COHEN A , ROIFMAN C M 
Published: July 2010

SUMMARYOmenn's syndrome is a fatal, autosomal-recessive combined immune deficiency characterized by several erythematous exfoliative eruptions, lymphadenopathy, hepatosplenomegaly, and elevated eosinophil count. In some of these patients an expansion of CD3+CD4−CD8− double negative (DN) T cell population was observed. We show here that the DN population represents a clonal expansion of T cells which preferentially use Vβ14 in their T cell receptor complex. Using polymerase chain reaction, we show that patient's DN cells express spontaneously high levels of IL-5, thus possibly explaining the abundance of eosinophils in this disorder. The increase of IgE observed in patients with Omenn's syndrome is unlikely to be related to IL-4 production, as IL-4 levels in patient samples were low. However, patient's low expression of interferon-gamma (IFN-γ), which has been reported to inhibit IgE production, may explain the elevated levels of IgE in this patient. The results thus highlight the importance of the inhibitory effect of IFN-γ on regulation of IgE production.
Low antibody affinity restricted to the IgA isotype in IgA nephropathy
Authors: LAYWARD L , ALLEN A C , HATTERSLEY J M , HARPER S J , FEEHALLY J 
Published: July 2010

SUMMARY
Antibody affinity affects the handling and behaviour of immune complexes, and experimental studies have shown that animals which produce predominantly low-affinity antibody are prone to immune complex deposition resulting in glomerulonephritis. In order to investigate the potential role of antibody affinity in the pathogenesis of IgA nephropathy, affinity of both IgA and IgG antibody isotypes during secondary response to systemic immunization with tetanus toxoid was studied in 20 patients with IgA nephropathy. Patients with IgA nephropathy produced IgA antibodies of significantly lower affinity than controls (P &lt; 0.001), whereas IgG antibody affinities were similar. Contrasting with controls, patients' IgA antibody affinity was inversely related to antibody concentration, with higher responders producing large amounts of low-affinity antibody. IgG antibody affinity increased with time, and maturation of IgG antibody affinity was similar in both controls and patients. IgA affinity in controls decreased with time, and this lack of IgA affinity maturation may explain the relative unimportance of IgA in normal systemic immunity. This temporal decrease in IgA affinity was not observed in patients with IgA nephropathy. The production of low-affinity IgA in IgA nephropathy may provide an explanation for the predominant deposition of IgA in this disease.
Soluble intercellular adhesion molecule-1 (sICAM-1) as a marker of disease relapse in idiopathic uveoretinitis
Authors: ZAMAN A G , EDELSTEN C , STANFORD M R , GRAHAM E M , ELLIS B A , DIRESKENELI H , D'CRUZ D P , HUGHES G R V , DUMONDE D C , WALLACE G R 
Published: July 2010

SUMMARYThis study reports the results of a point prevalence study of markers of endothelial dysfunction in the serum of patients with idiopathic uveoretinitis. sICAM-l, soluble endothelial leucocyte adhesion molecule (sELAM), anti-endothelial cell antibodies (AECA) and von Willebrand factor (vWF) levels were measured in 32 patients with isolated idiopathic uveoretinitis and seven with uveitis in association with systemic disease, using commercial and in-house ELISAs. Raised levels of AECA were found in 31% of patients with isolated uveitis, vWFin 28%, sELAM in 15.6% and sICAM-1 in 31%. Further analysis revealed that raised sICAM-1 levels were closely associated with recent relapse of disease (P=0.00003). Patients with accompanying systemic disease were found to have a similar prevalence of these serum abnormalities to those with isolated ocular disease. In conclusion, vascular endothelial dysfunction may contribute to pathogenesis in uveoretinitis, and in particular sICAM-1 may prove a marker of disease relapse in this condition.
Immunological diagnosis of childhood coeliac disease: comparison between antigliadin, antireticulin and antiendomysial antibodies
Authors: LERNER A , KUMAR V , IANCU T C 
Published: July 2010

SUMMARY
The immunological markers proposed to supplement intestinal biopsy for the diagnosis of coeliac disease are antigliadin, antireticulin and antiendomysial antibodies. These antibodies have been studied separately or compared as pairs, but no prospective comparison of all three antibodies in childhood coeliac disease exists. Thirty-four confirmed coeliacs were compared with nine non-coeliacs with pathological small intestines, and 32 children with a normal intestinal histology. Sera were examined for IgG- and IgA-antigliadin antibodies (AGA) by ELISA, and for IgA-antireticulin antibodies (ARA) and IgA endomysial antibodies (EMA) by indirect immunofluorescence. In active coeliac disease, IgA-EMA was the most sensitive (97%), while IgA-AGA the least sensitive antibody (52%). The specificity of IgA-AGA, IgG-AGA, IgA-ARA, IgA-EMA was 95%, 92%, 100% and 98%, respectively. Positive predicted values of ARA and EMA were comparable (97-100%), while EMA had the highest negative predicted value (98%). Compared with IgG-AGA, IgA-EMA titres better reflected variations in dietary gluten, and correlated best with intestinal pathology. Compared with AGA and ARA sensitivity, specificity and predictive values, EMA is the most reliable serological marker for the diagnosis of coeliac disease. It reflects dietary changes in gluten and correlates best with intestinal histopathology. Therefore, it should be considered the best of the three serological tests available for childhood coeliac disease.
Circulating intercellular adhesion molecule-1 (ICAM-1) in autoimmune liver disease and evidence for the production of ICAM-1 by cytokine-stimulated human hepatocytes
Authors: THOMSON A W , SATOH S , NÜSSLER A K , TAMURA K , WOO J , GAVALHR J , VAN THIEL D H 
Published: July 2010

SUMMARYA circulating form of the membrane-bound ICAM-1 (CD54). a ligand for lymphocyte function-associated antigen-1 (LFA-I), has recently been identified in normal human scrum. In this study. scrum levels of soluble ICAM-1 (sICAM-1) were determined by sandwich ELISA both in normal healthy individuals of both sexes and in subjects with autoimmune liver diseases. Patients with primary biliary cirrhosis (PBC). primary sclerosing cholangitis and chronic active hepatitis (autoimnune) showed significant elevations in sICAM-1 compared with normal healthy subjects. The median level in PBC was approximately seven-fold above normal. Significant elevations in sICAM-1 were also detected, however, in patients with inactive alcoholic cirrhosis, suggesting that impaired liver clearance might at least in part account for the increased serum levels seen in patients with autoimmune liver disease. In patients with PBC. sICAM-I levels were related to summary assessment of disease severity (Child-Pugh classification) and correlated significantly with serum biochemical indices of liver function, including measures both of cholestasis and liver cell injury. In contrast, serum levels of E-selectin did not differ significantly from healthy controis. Although it has been suggested that peripheral blood mononuclear cells (PBMC) may be a source of sICAM-I. investigation of ICAM-I gene expression by reverse transcriptase polymerase chain reaction revealed similar basal levels of ICAM-1 message in PBMC of normal individuals and those with active PBC. This suggests that PBMC may not be a significant source of sICAM-1 in this disease. Similar increases in ICAM-I mRNA expression were found in cultured, concanavalin A (Con A)-stimulated lymphocytes of both PBC patients and controls. Significantly, stimulation of cultured, normal human hepatocytes with proinflammatory cytokines and endotoxin induced cell surface expression of ICAM-1 and the secretion/shedding of sICAM-1 into the hepatocyte culture medium. This new finding suggests that hepatocytes may bean important sourceofsICAM-1 in autoimmune and other chronic liver diseases. The possible role of sICAM-1 in inflammatory disorders remains to be determined.
Expression of high-affinity IL-4 receptors on human melanoma, ovarian and breast carcinoma cells
Authors: OBIRI N I , SIEGEL J P , VARRICCHIO F , PURI R K 
Published: July 2010

SUMMARYIt has previously been shown that murine sarcoma cells express high-affinity IL-4 receptors (1L-4R) which are internalized after binding to the ligand (Puri et al., Cancer Res 1991; 51:3011–7). We have also reported that human renal cell carcinoma cells express high-affinity IL-4R. and IL-4 inhibits tumour growth in vitro (Obiri et al, J Clin Invest 1993; 91:88). In this study we investigated the expression and function of IL-4R on other human solid tumours. Human melanoma, ovarian carcinoma and breast carcinoma cell lines were assessed for the cell surface expression of IL-4R by radio-ligand receptor binding and for IL-4R gene expression by Northern blot analysis. Primary cultures of mesothelioma and neurofibrosarcoma cells were similarly investigated. Human melanoma, ovarian carcinoma and breast carcinoma cell lines expressed IL-4R on their cell surface with a dissociation constant (Kd) of 140-549 pM. These tumour lines expressed a single 4 kb species of mRNA for IL-4R. Similarly, primary cultures of mesothelioma and neurofibrosarcoma cells were positive for the IL-4R mRNA by Northern blot analysis. Fresh, non-cultured mesothelioma and neurofibrosarcoma tumour sections were also positive for the presence of IL-4R as determined by immunohistochemistry of frozen sections using anti-IL-4R antibody. In order to study possible functions of IL-4R, we evaluated the effects of 11.-4 on cell growth and its effect on MHC antigen expression in the presence or absence of interferon-gamma (IFN-γ)- In tissue culture, IL-4 reduced the growth of tumour cell lines and primary cell cultures studied. IL-4 had very title effect on MHC class I antigen expression on ovarian, breast and melanoma cell lines; however. MHC class I (HLA-DR) expression was enhanced on melanoma and breast carcinoma cells. IL-4 also enhanced the IFN-γ-induced class II expression on melanoma and breast carcinoma cells. Taken together, our observations indicate that IL-4R are expressed on a variety of human solid tumours and these receptors may be functional. IL-4 alone and in combination with IFN-γ may play a role in host immune response against cancers.