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F Tron

Publications and source records attributed to F Tron.

At least 73 records · Page 4Linked to original sources
PubMed1995

[Future vaccines].

Powerful genetic and immunological techniques allow the production of new vaccines. Recombinant proteins and synthetic peptides represent new categories of subunit vaccines, illustrated, respectively, by recombinant hepatitis B vaccines and a peptide-derived malaria vaccine. Virus and bacteria can be used as vectors of foreign genes encoding antigens of vaccinal interest, to build-up new forms of live vaccines. One may expect from these new strategies of vaccine production a better control of viral, bacterial and parasitic diseases and a dramatic change in vaccine recommendations for children and adults.

Adult↗
PubMed1995

During HIV infection, CD4+ CD38+ T-cells are the predominant circulating CD4+ subset whose HLA-DR positivity increases with disease progression and whose V beta repertoire is similar to that of CD4+ CD38- T-cells.

Three-color automated flow cytometry was carried out on peripheral blood CD4+ and CD8+ T-lymphocytes of 42 HIV-positive patients using tri-color anti-CD4 or anti-CD8, phycoerythrin-anti-CD38, and fluorescein-anti-HLA-DR, mAbs to elucidate further the T-cell activation hypothesis recently proposed to explain CD4+ T-cell abnormalities observed during HIV infection. CD4+ CD38+ T-cells constituted the major part of circulating CD4+ T-cells in HIV-infected patients and their HLA-DR molecule positivity increased as their disease progressed. The level of CD38 and HLA-DR expression on CD4+ T-cells was positively correlated to that of CD8+ T-cells and to the level of beta 2-microglobulin. Next, to determine whether CD38 expression was associated with a selective expansion or deletion of V beta gene-defined subsets, we compared the V beta gene frequencies between CD38+ and CD38- T-cells from HIV-infected CDC stage II patients using 13 mAbs specific to V beta families. While selective expansion of certain V beta families was observed in CD4+ and CD8+ T-cells the T-cell receptor V beta subset distribution was similar among CD38+ and CD38-, CD4+ and CD8+ T-cells, suggesting that CD38+ expression was either independent of an HIV-encoded antigen-driven process or rather indicative of T-cell immaturity. It is proposed that the phenotype of circulating CD4+ and CD8+ T-cells of HIV-infected patients is a feature of two different mechanisms: (i) an in vitro activation state responsible for increased DR expression and selective expansion of V beta gene-defined subsets, and (ii) T-cell immaturity due to an increased turnover of these cells and accounting for increased CD38 expression.

ADP-ribosyl Cyclase↗
PubMed1995

An idiotype D23-bearing polyspecific, murine anti-DNA monoclonal antibody forms glomerular immune deposits. Pathogenic role of natural autoantibodies?

Identification of the immunochemical and structural properties of pathogenic anti-DNA antibodies is a major goal for understanding their origins and the mechanisms whereby they induce tissue lesions. Herein, we report on the production of an IgG2a,k anti-DNA monoclonal antibody (4B1), derived from a 12-month-old (NZB x NZW)F1 lupus mouse, able to form glomerular immune deposits. mAb 4B1 is a polyspecific antibody able to bind to ssDNA, actin, tubulin, cardiolipin and to laminin as shown by solid phase ELISAs. Indirect immunofluorescence labeling of HEp-2 cells gave a cytoplasmic staining pattern similar to that obtained with anti-cytoskeleton antibodies. Western blot analysis demonstrated that mAb 4B1 bore idiotype D23, previously shown to be characteristic of natural antibodies derived from normal mice. After injecting the 4B1-secreting hybridoma intraperitoneally into normal (NZW x BALB/c)F1 mice, glomerular immune deposits were observed along the capillary wall. These deposits contained mainly IgM, IgG2a and mAb 4B1, as demonstrated by direct immunofluorescence using a biotinylated-rat anti-4B1 idiotype mAb and kidney eluate analysis. Nucleotide sequence analysis of the VH and VL genes showed that mAb 4B1 is encoded by VH Q52, DSP2.9 and JH2 genes with minimal mutations and by VK8 very similar to the canonic D23 light chain, and JK1 germline genes. No arginine residues were observed in the VH CDR and both chains lacked N-segment addition. Thus, no structural characteristics deduced from the primary structure of mAb 4B1 could explain its pathogenic potential. However, the immunochemical and structural properties suggest that autoantibodies closely related to natural autoantibodies may be pathogenic.

Amino Acid Sequence↗
PubMed1995

Comparison of activation marker and TCR V beta gene product expression by CD4+ and CD8+ T cells in peripheral blood and lymph nodes from HIV-infected patients.

Since lymphoid organs constitute the site of active and progressive HIV disease, analysis of their lymphocytes may provide more accurate information on T cell abnormalities than that obtained from studying peripheral blood lymphocytes. The objective of this study was to compare the expressions of activation markers and T cell receptor (TCR) V beta gene products by CD4+ and CD8+ T cells in lymph nodes (LN) and peripheral blood (PB) from healthy individuals and asymptomatic HIV-infected patients to determine whether anomalies that could be identified at the HIV replication site could support the hypothesis of T cell activation by HIV-encoded antigens or superantigens. CD4+ and CD8+ T cells in paired LN and PB obtained from six healthy controls and five asymptomatic HIV-infected individuals were analysed by flow cytometry, using anti-CD38, anti-HLA-DR and 13 anti-V beta MoAbs that cover, approximately, 45% of the T cell repertoire. Analysis of T cell activation marker expression indicated that the percentages of CD4+ and CD8+ T cells bearing CD38 or CD38 and HLA-DR molecules were higher in patients than in controls and, in patients, higher in LN than in PB. Comparison between the V beta repertoires of CD4+ and CD8+ T cells in LN and PB showed that, in each healthy individual, a limited number of V beta families expressed by CD4+ or CD8+ T cells had different repartition in LN and PB, whereas in each HIV+ patient, more V beta families exhibited different distributions and these differences recurred among certain V beta segments, such as V beta 5.3 and V beta 21 in the CD4+ T cell population and V beta 5.2/5.3, V beta 12 and V beta 21 in the CD8+ T cell population. Taken together, these data argue for a skewed TCR repertoire in HIV infection and sustained activation of T cells by HIV-encoded antigens at the site of HIV replication, and further demonstrate that a high proportion of CD4+ T cells are in an activation state that may, indirectly, participate in their functional abnormalities.

Adult↗
PubMed1995

Quantitation of human immunodeficiency virus type 1 DNA by two PCR procedures coupled with enzyme-linked oligosorbent assay.

Two quantitative PCR methods with our nonisotopic enzyme-linked oligosorbent assay (ELOSA) in microtiter plate format were developed for quantitation of human immunodeficiency virus type 1 (HIV-1). Quantitative competitive PCR (QC-PCR) was based on the coamplification of the wild-type nef region with a mimic competitive nef gene template carrying mutations in the capture region. Correlation of wild-type HIV-1 nef DNA to mimic template copy number permitted quantitation of HIV-1 copy numbers in the range of 20 to 2,000 copies per micrograms of DNA. Internally controlled PCR (IC-PCR) was based on coamplification of the nef region and the ras gene as an internal endogenous standard. Correlation to known amounts of HIV-1 DNA permitted quantitation by IC-PCR of HIV-1 copy numbers in the range of 10 to 2,000 copies per microgram of DNA. QC- and IC-PCR-ELOSA were performed on a panel of 53 seropositive patients and 12 seronegative controls. The methods showed similar coefficients of variation below 24%. Quantitations by QC- and IC-PCR-ELOSA were identical for 77% of patient samples. The copy level ranged between 443 +/- 156 and 21,453 +/- 13,511 copies per 10(5) CD4 cells for asymptomatic and AIDS patients, respectively. The simplicity and reliability of QC- and IC-PCR-ELOSA methods make them appropriate for routine laboratory use in the quantitation of viral and bacterial DNAs.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Catastrophic antiphospholipid syndrome with fatal acute course in rheumatoid arthritis.

A 34-year old woman, with a 3 yr history of severe seropositive rheumatoid arthritis (RA) with lupus anticoagulant and anticardiolipin antibodies, developed a massive anterior myocardial infarction and ischemia of the lower extremities, with disseminated intravascular coagulation resulting from extensive tissue damage. Seven days after admission, she died of severe heart failure complicated by ventricular fibrillation. To our knowledge, this is the first documented case of fatal acute antiphospholipid syndrome in RA.

Adult↗
PubMed1994

[Lupus diseases].

Systemic lupus erythematosus is a multifactorial, non organ-specific autoimmune disease. Studies of the disease in humans, of spontaneous murine models and of induced experimental models have made it possible to identify the various factors involved. These factors act on the immune system, the abnormalities of which include polyclonal B cell activation, selection of autoreactive B clones by autoantigen, and intervention of helper T cells. Other abnormalities, such as disturbance of the idiotypic network and alteration of suppressor T cell function, are not excluded.

Animals↗
PubMed1994

Structural characterization of an (NZB x NZW)F1 mouse-derived IgM monoclonal antibody that binds through V region-dependent interactions to murine IgG anti-DNA antibodies.

Among B/W-derived IgM mAb, 12.5H was selected because of its ability to recognize, in solid phase ELISAs, IgG mAb with DNA-binding activity. mAb 12.5H bound preferentially to IgG2a mAb and did not react with B/W- or BALB/c-derived IgG2a mAb with no DNA-binding activity, suggesting V region-mediated interactions. mAb 12.5H also bound to IgG2a isolated from the sera of old B/W mice but did not react with Ig present in the sera of young B/W (< 6 months) or BALB/c mice. Further analysis of IgM/IgG interaction showed that the binding of 12.5H to IgG polyclonal anti-DNA antibodies could be inhibited by DNA and that mAb 12.5H bound to the F(ab')2 fragments of B/W-derived IgG2a anti-DNA mAb, demonstrating that the interaction occurred through the variable regions of the molecules. When the antigen-binding capacity of mAb 12.5H was evaluated, it was demonstrated to bind to self-antigens such as myosin, actin, tubulin and histones, to bind poorly to ssDNA and not to react with dsDNA. mAb 12.5H gave a cytoplasmic staining pattern by indirect immunofluorescence on HEp-2 cells. Nucleotide sequence analysis of the H and L V genes showed features previously demonstrated to be recurrent in two categories of SLE autoantibodies, i.e. arginine residues in the VHCDR3 and at position 96 on the light chain, both considered to be characteristic of antibodies reacting with dsDNA and acidic amino-acid residues in VHCDR2 reported to be frequent on antihistone antibodies. Taken together, these results show that the B/W mouse repertoire contains IgM autoantibodies: (i) that react in an idiotypic manner with DNA binding antibodies and (ii) that, because of structural characteristics, may constitute the common precursor of different categories of SLE autoantibodies, and the prototype of the idiotypically connected SLE autoantibodies accounting for the production of autoantibodies upon immunization with cognate idiotype and the experimental model of cross-idiotype-induced lupus.

Amino Acid Sequence↗
PubMed1994

Prevalence and evolution of anticardiolipin antibodies in giant cell arteritis during corticosteroid therapy. A prospective study of 20 consecutive cases.

IgG and IgM anticardiolipin antibodies (aCA) were studied prospectively in 20 consecutive patients (12 females, eight males, mean age 74.6 +/- 14 yr, range 62-86 yr) with giant cell temporal arteritis before and during corticosteroid therapy (days 7, 30, 90 and 180). IgG-aCA were present in 10 out of 20 cases and in nine out of 12 with positive temporal artery biopsy but were not found in 20 paired control subjects. During steroid therapy aCA levels returned to within the normal range in 60% of patients with positive aCA at day 7 and in 80% at day 30. In two cases aCA persisted during the 6-month follow-up despite clinical and biological success. No association was found between aCA and thrombotic events.

Adrenal Cortex Hormones↗
PubMed1994

Overlapping distribution of autoantibody specificities in paraneoplastic pemphigus and pemphigus vulgaris.

Paraneoplastic pemphigus is an autoimmune bullous skin disease in which autoantibodies immunoprecipitate a characteristic antigenic complex. The objective of this study was to analyze by immunoblotting and immunoelectron microscopy the autoimmune response in five patients with clinical and immunohistologic features typical of paraneoplastic pemphigus. In a first series of experiments, immunoblotting and immunoelectron microscopy were performed using anti-human whole Ig. Although immunoblotting results were consistent with the autoantibody specificities previously described in paraneoplastic pemphigus sera, immunoelectron microscopy demonstrated the presence of Ig deposits on desmosomal plaques, on hemidesmosomes and, surprisingly, on both the extracellular part of desmosomes and the keratinocyte plasma membrane. In a second series of experiments, immunoblotting and immunoelectron microscopy were carried out using antihuman IgG subclasses. The major observation was that two sera contained, in addition to the anti-desmoplakins I-II, anti-185-kD and anti-230-kD autoantibodies, autoantibodies that stained the desmoglea by indirect immunoelectron microscopy and bound to a 130-kD polypeptide by immunoblotting. One serum was particularly demonstrative: IgG1 bound to the 250- and 220-kD bands corresponding to desmoplakins I and II on immunoblots and to the desmosomal plaques of keratinocytes in immunoelectron microscopic preparations; IgG3 recognized a 185-kD immunoblotting band and hemidesmosomes and desmosomal plaques by immunoelectron microscopy; IgG4 bound to the 130-kD immunoblotting band of pemphigus vulgaris and labeled the desmoglea and the keratinocyte plasma membrane by immunoelectron microscopy. These results demonstrate that the paraneoplastic-pemphigus autoimmune response involves both intracellular and extracellular desmosomal antigens and suggest an overlapping distribution of autoantibody specificities among autoimmune bullous skin diseases.

Aged↗
PubMed1994

Thiopronine-induced herpetiform pemphigus: report of a case studied by immunoelectron microscopy and immunoblot analysis.

We report a case of herpetiform pemphigus induced by thiopronine. Direct immunoelectron microscopy performed on peribullous skin showed IgG deposits predominantly located in the extracellular portion of desmosomes. By immunoblot analysis using bovine tongue extracts as the antigen, the patient's serum recognized a 160-kDa polypeptide which comigrated with desmoglein I. This study underlines the contribution of immunoblot analysis to the diagnosis of atypical cases of pemphigus, and confirms that herpetiform pemphigus may be a clinical variant of pemphigus foliaceus.

Aged↗
PubMed1993

Antibodies to Sm, RNP and SSB detected by solid-phase ELISAs using recombinant antigens: a comparison study with counter immunoelectrophoresis and immunoblotting.

Sera from 64 patients with systemic lupus erythematosus (SLE) were tested for the presence of anti-Sm, anti-RNP, and anti-SSB antibodies using commercially available solid-phase enzyme-linked immunosorbent assays (ELISAs) and recombinant nuclear proteins as substrates. The results were compared to those obtained with counterimmunoelectrophoresis (CIE) and immunoblotting (IBT) using a rabbit thymus extract (RTE) as the substrate. The ELISAs detected antibodies to Sm, RNP, and SSB in, respectively, 25%, 36%, and 15% of the SLE sera. Neither IBT-positive/ELISA-negative nor CIE-positive/ELISA-negative sera were found, regardless of the specificity considered, suggesting that ELISAs using recombinant nuclear antigens are highly sensitive. Discrepancies were observed between the results obtained with these different techniques. In addition to sera positive by both IBT and ELISA but negative by CIE, a substantial number of sera had ELISA-detectable anti-Sm, anti-RNP, and anti-SSB antibodies which failed to react with the corresponding polypeptides by IBT. The reasons for ELISA/IBT discrepancies were explored; however, no single explanation was found. Instead, a higher sensitivity of the ELISA to detect antibodies directed against certain polypeptides, the possible inability of IBT using RTE as the substrate to detect antibodies reacting with conformational antigenic determinants, and false-positive reactions in the ELISAs were suggested. Thus, it is still advisable to perform both IBT and ELISAs simultaneously in well-defined autoimmune diseases to further analyze the potential advantages of ELISAs using recombinant antigens.

Animals↗
PubMed1993

The impaired in vitro production of interleukin-2 in HIV infection is negatively correlated to the number of circulating CD4+DR+ T cells and is reversed by allowing T cells to rest in culture: arguments for in vivo CD4+ T cell activation.

In HIV infection, several arguments suggest a certain degree of CD4+ T cell activation which might contribute to lymphocyte dysfunctions. To investigate this possibility, we determined the phenotypes of circulating CD4+ T cells using monoclonal antibodies directed to activation markers and examined whether the defective in vitro interleukin-2 (IL-2) production by purified CD4+ T cells isolated from infected individuals was reversible in rested cultured T cells, a phenomenon suggestive of in vivo CD4+ T cell exhaustion. The number of CD4+ T cells expressing HLA-DR molecules was the same as that observed in controls, remained constant throughout the course of HIV infection, and constituted a major part of circulating CD4+ T cells. In CDC stage II group, the increased percentage of CD4+DR+ T cells was also associated with an increased expression of early activation markers. Defective IL-2 production in vitro was restored when CD4+ T cells were allowed to rest in culture. In addition, the number of circulating CD4+DR+ T cells correlated negatively with the in vitro IL-2 production induced by phytohemagglutinin and phorbol ester by freshly isolated CD4+ T cells. Taken together, these data suggest that in vivo activated CD4+ T cells may participate in the immune abnormalities of HIV infection.

Antibodies, Monoclonal↗
PubMed1993

Brunsting-Perry cicatricial bullous pemphigoid: a clinical variant of localized acquired epidermolysis bullosa?

An 84-year-old man who had the typical clinical features of Brunsting-Perry cicatricial pemphigoid is described. Direct immunofluorescence microscopic examination of salt-split skin revealed linear deposits of IgG and C3 on the floor of the artificial bullae. Direct immunoelectron microscopic examination of peribullous skin showed dermal cleavage level below the lamina densa and granular deposits of IgG and C3 attached to and below the lamina densa in a pattern identical to epidermolysis bullosa acquisita. These findings suggest that Brunsting-Perry cicatricial pemphigoid may represent a clinical variant of epidermolysis bullosa acquisita.

Aged↗
PubMed1993

Immunofluorescence and immunoelectron microscopy analyses of a human monoclonal anti-epithelial cell surface antibody that recognizes a 185-kD polypeptide: a component of the paraneoplastic pemphigus antigen complex?

We recently reported the production of a human monoclonal antibody (MoAb) derived from a patient with pemphigus vulgaris (PV) that binds to the keratinocyte membrane and reacts with a 185-kD polypeptide by immunoblot analysis. We have since examined the tissue specificity of that MoAb, F12. By indirect immunofluorescence (IIF), F12 stained both the cell membrane and the basement membrane zone of stratified squamous epithelia. Moreover, MoAb F12 stained other epithelial tissues, such as urinary bladder, small bowel, thymus, and liver, and non-epithelial tissues, such as myocardium. Indirect immunoelectron microscopy (IIEM) analysis showed that MoAb F12 bound to a component common to desmosomal and hemidesmosomal plaques and to zona adherens-type junctions between hepatocytes and bile duct cells. Inhibition experiments were then performed with sera from patients with pemphigus vulgaris, pemphigus foliaceus, paraneoplastic pemphigus, or bullous pemphigoid. Three sera blocked F12 reactivity; two were from paraneoplastic pemphigus patients and the other was from the pemphigus vulgaris patient whose peripheral blood lymphocytes were used to make F12. All these sera recognized a 185-kD band that co-migrated with the polypeptide labeled by MoAb F12 on immunoblots. In addition, the IIF and IIEM staining patterns of MoAb F12 were similar to those observed with sera from two patients with paraneoplastic pemphigus. These observations suggest a relationship between MoAb F12 and the autoimmune response characterizing paraneoplastic pemphigus patients' sera.

Antibodies, Monoclonal↗
PubMed1993

Local and systemic activation of the whole complement cascade in human leukocytoclastic cutaneous vasculitis; C3d,g and terminal complement complex as sensitive markers.

We have studied complement activation both in plasma samples and in lesional skin from patients with leukocytoclastic cutaneous vasculitis (LCV). Enzyme immunoassay (EIA) quantification of the complement activation markers, C3d,g and the terminal complement complex (TCC) in plasma, showed that their levels were significantly increased in 66% and 55% of the patients, respectively (n = 29) compared with healthy controls, whereas the standard measurements of C3, factor B, C1q, C4 and C2 were generally within normal range. Elevations of C3d,g and TCC levels in plasma were significantly correlated. Importantly, a significant correlation was found between the severity of the vasculitis and both C3d,g and TCC plasma levels. Immunofluorescence studies of skin biopsy specimens demonstrated simultaneous presence of perivascular dermal deposits of C3d,g and TCC in lesional skin from 96% and 80% respectively of the patients (n = 25). There was a significant correlation between the intensity of the deposits of both markers. Clusterin, a TCC inhibitory protein, was always found at the same sites of perivascular TCC deposits. Immunofluorescence studies at the epidermal basement membrane zone (BMZ) revealed in each case deposits of C3d,g which were accompanied by TCC deposits in 52% of the biopsy specimens. These data demonstrate that there is a local and systemic activation of the whole complement cascade in human LCV. The presence of both C3d,g and clusterin-associated TCC perivascular deposits suggests an intervention of a regulatory mechanism of local complement activation in LCV. Finally, measurement of plasma C3d,g and TCC appears to be a sensitive indicator of systemic complement activation and disease severity in LCV.

Aged↗
PubMed1993

[Extensive fibrous endocarditis as first manifestation of systemic lupus erythematosus].

BACKGROUND: Cardiac abnormalities, such as myocarditis, pericarditis or verrucous endocarditis (Libman-Sacks endocarditis) occur in about one third of patients with systemic lupus erythematosus. This study describes an unusual aspect of endocardial involvement. CASE REPORTS: Case no. 1: A 14 year-old girl was admitted 3 months after acute hemichorea because of heart failure plus biological inflammatory findings. Echocardiography showed mitral insufficiency with enlargement of the left atrium and ventricle. There was some infiltration involving the endocardium of the left ventricle, the chordae tendinae and the mitral valve. The titres of anti-DNA and anti-nuclear antibodies were elevated while the serum hemolytic complement was depressed. Skin biopsy showed IgG, IgM and C1q deposits along the dermoepidermal junction. Corticosteroids, diuretics and vasodilator drugs failed to completely cure the heart failure; the mitral insufficiency required mitral valve replacement 21 months later. Pathological examination showed extended fibrotic changes of the endocardium. Case no. 2: A 4 year-old boy was admitted for acute heart failure due to mitral insufficiency, associated with biological inflammatory findings. Echocardiography showed mitral insufficiency and enlarged left atrium and ventricle. Anti-DNA and anti-nuclear antibody titres were elevated. The patient was given antibiotics followed by corticosteroids and immunosuppressive drugs. The persistence of the mitral insufficiency required mitral valve replacement 7 months later. Pathological examination showed fibrotic changes of the endocardium. Exacerbation of the inflammatory process was seen 2 months after surgery, with development of diffuse proliferative lupus nephritis. The patient died of kidney failure and neurological complications, 44 months after cardiac surgery. CONCLUSION: In both patients, the systemic lupus erythematosus was revealed by endocardial involvement, a complication that is usually seen later. The endocardium changes responsible for mitral insufficiency and requiring valve replacement in these two cases were different from those described as verrucous endocarditis in classical forms of the disease.

Adolescent↗