bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epitope mapping with synthetic peptides of 52-kD SSA/Ro protein reveals heterogeneous antibody profiles in human autoimmune sera
Authors: RICCHIUTI V , BRIAND J P , MEYER O , ISENBERG D A , PRUIJNJ G , MULLER S 
Published: August 2010

SUMMARYThe reactivity of autoantibodies present in the sera of 489 palicnts with Sjögren's syndrome (SS), systemic lupus crythematosus (SLE) and other autoimmune diseases was investigated by ELISA using recombinani 52-kD SSA/Ro protein (rRo52) and 39 overlapping synthetic peptides representing the entire sequence of Ro52. We report that IgG antibodies reacting with rRo52 were present in the sera of a large number of patients with SS (67% of patients with primary SS and 46% of patients with SS associated with SLE), whereas they were less frequent (10–25%) in SLE, rheumatoid arthritis (RA), juvenile chronic arthritis (JCA) and mixed connective tissue disease (MCTD), and absent in scleroderma. Among the 39 peptides tested, live were recognized by sera from 30–65% of patients with SS, namely peptides representing residues 2 11, 107 122, 107 126, 277 292 and 365 382. Patients with JCA had raised levels of IgG antibodies reacting with peptides 2 11 and 365 382, and 51% of patients with MCTD had raised levels of IgG antibodies reacting with peptide 365 382. None of the five peptides was recognized by more than 20% of sera from patients with SLE and RA. Interestingly, and of importance in the field of diagnostic tests based on peptides, the reactivity of antibodies to the Ro52 synthetic peptides varied greatly according to the origin of sera. Inhibition experiments using either patients' sera or antibodies induced in rabbits against Ro52 peptides showed that the four domains 2-11. 107 122, 277 292 and 365 382 are accessible on the surface of the Ro52 protein. These regions may thus be involved in the induction of specific antibodies in autoimmune patients.
Selective increase of activation antigens HLA-DR and CD38 on CD45RO+ T lymphocytes during HIV-1 infection
Authors: KESTENS L , VANHAM G , VEREECKEN C , VANDENBRUAENE M , VERCAUTEREN G , COLEBUNDERS R L , GIGASE P L 
Published: August 2010

SUMMARYInfection with HIV results in a progressive depletion of CD4* T cells and leads to significant in vivo lymphocyte phenotype changes. In this regard, the expression of HLA-DR and CD38 on CD8* T cells has been shown to increase dramatically with disease progression. We investigated the expression of both aetivation markers on CD4* T cells in HIV-1-infected subjeets at different clinical stages of infection and compared the in vivo activation of CD4* T cells with parameters of viral activity and CD8* T cell activation. Eresh peripheral venous blood was obtained from 54 HIVinfeeted subjects and from 28 uninfected healthy controls. Three-colour immunophenotyping of the CD4’T Cell subset showed that the proportion of CD4* T cells expressing HLA-DR (10% in HIV negative controls) or CD38 (62%. in HIV-negative controls) was higher in asymptomatic (P &lt; 0·05 for CD38) and symptomatic (P&lt; 0.001 for HLA-DR and CD38) HIV-infected subjects than in controls, whereas the proportion of CD4* T cells expressing CD45RO (54% in controls) remained relatively unchanged. Simultaneous expression of HLA-DR and CD38 on CD4 * T cells increased from 2·3% in controls to 11% (P&lt;0·001) in asymptomatic and 22% (P &lt; 0·001) in symptomatic HIV-infected subjects. This relative increase of CD38 and HLA-DR expression occurred mainly on CD4* T cells co-expressing CD45RO. Changes in expression of HLA-DR and CD38 on CD4 * T cells correlated with similar changes on CD8 * T lymphocytes, with the presence of HIV antigen in the circulation, and with the disease stage of HIV infection.
HIV-1 induces tumour necrosis factor and IL-1 gene expression in primary human macrophages independent of productive infection
Authors: HERBEIN G , KESHAV S , COLLIN M , MONTANER L J , GORDON S 
Published: August 2010

SUMMARYCylokines such as tumour necrosis factor-alpha (TNF-a) and IL-Iβ may play a role in immunopalhogcncsis of AIDS, We studied early effects (05-48 h) of monocytotropic (ADA) or tymp ho tropic (1MB) strains of HIV-1 on TNF-α and IL-1β mRNA expression in primary human macrophages by a semi-quantitative reverse transcriptase-polymcrase chain reaction (RT-PCR) assay. Three-day-old monocyte-derived macrophages were exposed either to tissue culture supernatants containing virus (at multiplicity of infection (m.o.i.) of 005) or to control supernatants frceofvirionsandgpI20. ADA strain, but not IIIB. replicated in primary tissue culture-differentiated macrophages (TCDM). Soluble CD4 (sC D4) was used to inhibit binding of both strains to macrophages. We found that TNF-arand IL-lβ gene expression was induced by both strains 0-5-3 hafter addition of virus, and that enhanced expression of both cytokines was inhibited by sCD4. We conclude that C D4-dependcnl binding lo ihc cell surface is sufficient to enhance TNI′-α and ll.-lβ mRNA. whereas productive viral replication in primary human macrophages is not required. Therefore, similar pathways regulate gene expression of TNF-a and IL-Iβ by macrophages during initial infection by HIV-1 in vitro.
H-2b restriction of the immune response to the pl26Plasmodium falciparumantigen
Authors: BANIC D M , DELPLACE P , MAZINGUE C , CAMUS D 
Published: August 2010

SUMMARYInbred BALB/c (H-2d), CBA (H-2k) and C57Bl/6 (H-2%) mice immunized with Plasmodium falciparum schizonls or culture supernatcs develop antibodies of different anligcnic specificities. It has been observed that C57B1/6 mice were unable to produce deteelable antibodies against the pl26 antigen (native molecule and p73 or p50 processed fragments) compared with other inbred miee. Similar results were obtained using BALBeongenlc mice with a lack of p126 antibody response in H-2b mice, while H-2d and H-2k mice produced antibodies against the pl26. Lymphoeyte proliferation assays performed by incubation of spleen cells with immunopurified pl26 were positive for immunized BALB/c (H-2d) and congenic H-2d or H-2k mice. On the other hand, no lymphocyte stimulation was observed with either C57B1/6 (H-2b) or congenic H-2b miee. These results suggest an MHC restriction of the immune response against the entire pi 26 (found in schizonts) and its p73 and p50 naturally processed fragments (found in culture supernates).
Natural autoantibodies, IgG antibodies to tetanus toxoid and CD5+ B cells in patients with Mediterranean visceral leishmaniasis
Authors:   THE LEISHMANIA STUDY GROUP, LOUZIR H , BELAL-KACHMI L , SASSI A , LAOUINI D , BEN ISMAIL R , DELLAGI K 
Published: August 2010

SUMMARYNatural autoantibodies (NaAb) and IgG antibodies to tetanus toxoid (TT) were analysed in the sera of 38 children with active visceral leishmaniasis (VL) previously vaccinated with TT and in 30 healthy controls matched for sex and age. Patients exhibited high levels of NaAb to a panel of self antigens (tubulin, myosin. myoglobin, actin) contrasting to a low level of IgG to TT. Analysis of the circulating B cells in 26 untreated patients showed a low percentage of CD5+ per total B cells (3–66%, mean 36·6%) compared with 14 normal conirols (17·8–66·6%, mean 52·7%)(P&lt;0·001). Evaluation of these parameters after antimonial therapy showed a significant decrease of the level of the NaAb (P&lt;0.0005), and a spontaneous increase of the level of the IgG to TT without any vaccine boosting (P&lt;0·01). In contrast, there was a significant increase in CD5+ B cells (P&lt;0·0005). This result suggests that CD5+ B cells may be sequestrated in parasitized lymphoid organs and may be released after remission. These findings show that the polyclonal B cell activation that occurs during active VL involves mainly B cells bearing NaAb and are in favour of a functional dichotomy of B cells.
Antimicrobial action of antibodies againstGiardia muristrophozoites
Authors: BELOSEVIC M , FAUBERT G M , DHARAMPAUL S 
Published: August 2010

SUMMARYThe activities of immune serum and trophozoite-specific MoAb were examined in vitro and in vivo. Immune serum and anti-Giardia muris MoAb caused immobilization of the trophozoites in vitro and were cytotoxic for trophozoites in the presence of exogenous complement. Both immune serum obtained from experimentally infected mice and anti-G. muris MoAb admmistered directly into the duodenum of mice significantly reduced the number of trophozoites in the small intestine during the acute phase of the infection. These results suggest that serum antibodies play a central role in the elimination of the primary Giardia infection.
Suppression of pulmonary injury in experimental ‘Goodpasture's syndrome’ by deoxyspergualin (DSP)
Authors: LAN H Y , NIKOLIC-PATHRSON D J , ZARAMA M , KERR P G , ATKINS R C 
Published: August 2010

SUMMARYDSP is a potent immunosuppressive drug which can prevcnt allograft rejection and suppress acute rejection episodes. In this study, the ability of DSP to suppress pulmonary injury in experimental Goodpasture's syndrome was investigated. Passive accelerated anti-glomerular basement membrane (GBM) disease was induced in rats by priming with rabbit IgG. followed 5 days later by injection of rabbit anti-GBM serum (day 0). Groups of five animals were treated with DSP (5 mg/kg iniraperitoneally per day) or saline (untreated) from day 0 until being killed on days 1,7,14or21. At day I, both DSP-treated and untreated animals exhibited similar pulmonary haemorrhage, oedema, and prominent perivascular leucocyte infiltration. Untreated animals subsequently developed severe widespread pulmonary damage including granulomatous lesions and extensive fibrosis, which correlated with infiltration of macrophages and immune-activated (IL-2R′) mononuelcar cells (P&lt;0·01). Tumour necrosis factor-alpha (TNF-α), a known mediator of acute lung damage, was produced by pulmonary mononuclear cells throughout the experimental course. In contrast, DSP treatment resolved pulmonary haemorrhage, prevented the appearance of granulomatous lesions, and resulted in a histologically normal lung structure by day 21. This improvement was associated with a marked suppression of maerophage infiltration (P&lt;0·001 versus untreated), accumulation of immune activated (IL-2R′) mononuelear cells (P&lt;0·05 versus untreated), and TNF-α production (P&lt;0.05 versus untreated). DSP treatment also suppressed the deposition of rat anti-rabbit IgG immunoglobulin and C3 along the alveolar basement membrane (P&lt;0·05 versus untreated). In conclusion, DSP suppressed pulmonary injury in accelerated anti-GBM disease by acting on the local cellular immune response and the systemic humoral immune response. Further studies are warranted to determine whether this could be a useful drug for the treatment of Goodpasture's syndrome in humans.
Expression of interferon-gamma (IFN-δ), IL-10, IL-12 and transforming growth factor-beta (TGF-β) mRNA in synovial fluid cells from patients in the early and late phases of rheumatoid arthritis (RA)
Authors: Bucht A , Larsson P , Weisbrot L , Thorne C , Pisa P , Smedegård G , Keystone E C , Grönberg A 
Published: August 2010

SUMMARYThe expression of immunoregulatory cytokines was investigated in freshly isolated synovial fluid mononuclear cells (SFMC) and peripheral blood mononuclear cells (PBMC) from patients with RA, using a quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay. IFN-γ, TGF-β, IL-10 and IL-12 (p40) transcripts were detected in SFMC of patients with early disease (&lt;1 year duration) as well as in patients with long standing arthritis (&gt;1 year). The expression of IFN-γ, IL-10 and IL-12 mRNA was increased in SFMC compared with RA PBMC. In addition, the expression was higher in RA SFMC than in PBMC from healthy control individuals. Immunoassay analysis of the secreted IL-12 heterodimer demonstrated increased levels in RA SF compared with levels found in serum from RA patients and control individuals. High levels of TGF-β mRNA were found in SFMC, but a significantly decreased TGF-β/β2-microglobulin (β2-M) ratio was found compared with PBMC from both patients and control individuals. IL-4 mRNA could not be detected, either in SFMC or in PBMC. Cytokine expression in RA PBMC did not differ from control PBMC, with the exception of a decreased TGF-β/β2-M ratio in RA patients with early disease. Our findings of IFN-7 mRNA and IL-12, but undetectable levels of IL-4 mRNA, suggest that the synovitis is characterized by a type 1 immune response. The presence of TGF-β and IL-10 mRNA indicates that immunosuppressive cytokines may also operate in the inflamed joint, although their level of expression may not be sufficient for down-modulation of immune activation.
A synthetic 10-kD heat shock protein (hsp10) fromMycobacterium tuberculosismodulates adjuvant arthritis
Authors: Ragno S , Winrow V R , Mascagni P , Lucietto P , Pierro F DI , Morris C J , Blake D R 
Published: August 2010

SUMMARYThe heat shock protein, hsp10, is an abundant protein in Mycobacterium tuberculosis (Mtb), its nucleotide sequence encoding a protein of 99 amino acids with a molecular mass of 10±7kD. This sequence is phylogenetically conserved, being represented by the GroES homologue of Escherichia coli. Hsp 10 and GroES are members of the chaperonin 10 family of molecular chaperones, and GroES is necessary for the optimal activity of GroEL, a member of the chaperonin 60 family and the E coli homologue of mycobacterial hsp65. Since hsp65 has been implicated in both experimental and human rheumatoid arthritis, we aimed to assess the immunomodulatory effects of its co-chaperonin, hsp10, in experimental arthritis. Our results show that an aqueous solution of a mycobacterial hsp10 delayed the onset and severity of adjuvant-induced arthritis in rodents when administered after disease induction but before joint involvement occurred. This biological activity was specific for the hsp10 of Mtb, since neither GroES nor the rat homologue was effective. Using synthetic hsp10 fragments, the activity was localized to the N-terminal region of the molecule. Assessment of circulating antibody levels to mycobacterial hsp10 and hsp65 indicated that all arthritic rats had increased litres to both hsp10 and hsp65: hsp10-treated rats showed further elevation of this humoral response not only to hsp10 but also to hsp65 when compared with the untreated arthritic control. This is the first report of the immunomodulatory activity of mycobacterial hsp10 in experimental arthritis, and exhibits a potential role for this co-chaperonin in pathophysiological situations.
Distribution of four polymorphisms in the tumour necrosis factor (TNF) genes in patients with inflammatory bowel disease (IBD)
Authors: Bouma G , Xia B , Crusius J B A , Bioque G , Koutroubakis I , von Blomberg B M E , Meuwissen S G M , Peña A S 
Published: August 2010

SUMMARY
In 153 patients with IBD, 64 with Crohn’s disease (CD), and 89 with ulcerative colitis (UC), as well as in 54 healthy controls (HC), the frequencies of four known di-allelic polymorphisms in the genes for TNF-α and lymphotoxin alpha (LTα) were investigated. In the Dutch population, the alleles of these four polymorphisms are present in only five combinations, called TNF haplotypes: TNF-C, -E, -H, -I, -P. Furthermore, the relation with the presence of perinuclear anti-neutrophil cytoplasmic autoantibodies (P-ANCA) was studied. A small, but statistically significant, association between the polymorphism at position -308 in the promoter region of the TNF-α gene and UC was found. The frequency of the uncommon TNF-α -308 allele 2 was found to be decreased in patients with UC compared with HC (allele frequency of allele 2 in UC patients 0±15 versus 0±25 in HC, P= 0±044). No significant differences in distribution of the TNF haplotypes were found between IBD patients and HC, although there was a tendency towards a higher frequency of the TNF-C haplotype in UC patients compared with controls (haplotype frequency 22%versus 13%; P= 0±19). No statistically significant differences in distribution of the TNF haplotypes were observed between P-ANCA-positive and P-ANCA-negative UC patients. The strength of the associations indicates that TNF genes are not markers for the predisposition to suffer from IBD. They may, however, be markers of subsets of patients with UC and CD.
Leucocyte activation by anti-lactoferrin antibodies bound to vascular endothelium
Authors: Peen E , Sundqvist T , Skogh T 
Published: August 2010

SUMMARYHuman polymorphonuclear neutrophil leucocytes (PMNL) prestimulated with the formylated tripeptide f-Met-Leu-Phe (fMLP) were activated to an immediate chemiluminescence (CL) response by polyclonal rabbit antibodies against human lactoferrin (Lf). This activation, indicating the formation of reactive oxygen species, was induced by intact IgG antibodies but could not be brought about by F(ab')2 fragments. Human Lf was also shown to adhere to the surface of cultured bovine aorta endothelial cells (BEC). When Lf-coated BEC grown on microcarrier beads were reacted with anti-Lf antibodies, an immediate CL response was achieved also with non-primed PMNL. Here, too, the reaction required intact IgG antibodies. Also, patient sera containing anti-Lf autoantibodies of IgG class were shown to activate fMLP-treated PMNL. The same effect was obtained (in a dose-dependent manner) with the gammaglobulin fraction from anti-Lf-positive patient serum. Further, anti-Lf-antibody-positive patient sera incubated with Lf-coated BEC beads were also able to activate non-stimulated PMNL to a chemiluminescence response. The results are discussed in relation to possible mechanisms of cell/tissue damage induced by anti-neutrophil cytoplasmic antibodies (ANCA).
Autoantibodies to human heat shock protein (hsp)60 may be induced by Escherichia coli groEL
Authors: Handley H H , Yu J , Yu D T Y , Singh B , Gupta R S , Vaughan J H 
Published: August 2010

SUMMARYThe 65-kD hsp from Mycobacterium tuberculosis has been reported to induce an autopathogenic subset of T cells in at least two animal models of autoimmune disease. Reports of increased expression of human hsp60 in the inflamed synovial tissue of rheumatoid arthritis (RA) patients, increased proliferation of RA synovial fluid T cells to mycobacterial hsp65, and increased levels of anti-mycobacterial hsp65 antibody in synovial fluid, have suggested that the highly homologous human (hu) hsp60 may be recognized as an autoantigen in RA patients. In the present study, we have examined by ELISA the serum IgG antibody levels to mycobacterial hsp65 and hu hsp60, as well as to the Escherichia coli hsp60, groEL, in patients with RA, systemic lupus erythematosus (SLE), Reiter’s syndrome, active tuberculosis, and normal controls. In all these groups, the levels of anti-groEL and anti-hu hsp60 were significantly higher than the anti-mycobacterial hsp65. Anti-hu hsp60 was positively correlated with anti-groEL, but not with anti-mycobacterial hsp65. Anti-hu hsp60 was competitively inhibited by either soluble groEL or hu hsp60, but little or none by mycobacterial hsp65. Reiter’s sera were found to have somewhat higher levels of anti-groEL and anti-hu hsp60 than did normal controls. We conclude that IgG anti-hu hsp60 autoantibodies arise primarily as a consequence of the humoral immune response to E. coli groEL through the recognition of cross-reactive epitopes.
Enhancing effect of oxygen radical scavengers on murine macrophage anticryptococcal activity through production of nitric oxide
Authors: Tohyama M , Kawakami K , Futenma M , Saito A 
Published: August 2010

SUMMARYWe examined the roles of reactive nitrogen intermediates (RNI) and reactive oxygen intermediates (ROI) in interferon-gamma (IFN-γ)-induced cryptococcostatic activity of murine peritoneal macrophages using NG-monomethyl-L-arginine (L-NMMA), a competitive inhibitor of RNI synthesis, and superoxide dismutase (SOD) and catalase, oxygen radical scavengers. IFN-γ-activated macrophages produced nitric oxide (NO) in a dose-dependent manner, as measured by increased nitrite concentration in the culture supernatant. IFN-γ also enhanced the suppressive effect on cryptococcal growth in a similar dose-dependent manner. The induction of killing activity and NO production by an optimal dose of IFN-γ (100 U/ml) was virtually suppressed by 500 μM L-NMMA. These results confirmed the importance of the RNI-mediated effector mechanism in anticryptococcal activity of macrophages. SOD and catalase significantly enhanced the cryptococcostatic activity of macrophages induced by a suboptimal dose of IFN-γ (20 U/ml). The augmenting effect of these reagents was mediated by NO, since they potentiated the production of NO by macrophages and their effects were totally blocked by L-NMMA. Our results indicate that the IFN-γ-induced anticryptococcal activity of macrophages is dependent mostly on RNI, and suggest that the ROI system down-regulates the effector mechanism for cryptococcostasis by suppressing the RNI system.
Allergenic epitopes of ovalbumin (OVA) in patients with hen’s egg allergy: inhibition of basophil histamine release by haptenic ovalbumin peptide
Authors: Honma K , Kohno Y , Saito K , Shimojo N , Horiuchi T , Hayashi H , Suzuki N , Hosoya T , Tsunoo H , Niimi H 
Published: August 2010

SUMMARYWe studied allergenic determinants that induce hypersensitivity to OVA, the major allergen in egg allergy, using immunoblot and histamine release assays. Immunoblot analysis demonstrated a part of the OVA epitope was in the C-terminal region comprising residues 347-385 (OVA347-385). Histamine was released from basophils of a patient with egg allergy upon stimulation with the OVA fragment corresponding to OVA347–385. Furthermore, detailed epitope mapping using overlapping peptides (residues 347-366, OVA-A; residues 357-376, OVA-B; and residues 367-385, OVA-C) in the OVA 347-385 region was carried out using the histamine release assay. In order for histamine release from basophils to occur, the allergen must possess two or more allergenic determinants located on the protein molecule at distances that would be equivalent to the distances between IgE molecules on the membrane surface. These results suggest that there are at least two epitopes that bind IgE antibodies on each OVA peptide. In addition, one epitope that binds IgE antibodies in two patients appears to reside in the haptenic peptide OVA357-366 (OVA-B1). The histamine release from basophils stimulated by OVA-B was completely inhibited by OVA-B1 in one of these patients. Similarly, OVA-B1 inhibited the histamine release produced by OVA-A in the other by more than 40%. These results suggest that haptenic synthetic peptides could regulate the allergic reaction in the effector phase if common epitope(s) recognized by IgE antibodies in the patients with egg allergy can be found. These are the first studies that provide an antigen-specific approach to inhibiting histamine release from basophils by a haptenic peptide recognized by IgE antibodies in an allergic disorder.