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F Tron

Publications and source records attributed to F Tron.

At least 91 records · Page 5Linked to original sources
PubMed1992

Development of the B cell anti-DNA repertoire in (NZB x NZW)F1 mice. Relationship with the natural autoimmune repertoire.

The relationship between pathologic anti-DNA and natural autoantibodies (Auto Ab) remains unclear. In particular, it has not yet been elucidated whether pathologic anti-DNA antibodies originate from and are regulated by the pool of natural Auto Ab. To address this question, a large number of Ig-secreting hybridomas were derived from the unstimulated splenocytes of B/W mice, newborn to 12 mo of age, and their binding activities against a panel of self-Ag (DNA, actin, tubulin, myosin, and myoglobin), isotype, idiotypic determinants, and VH gene utilization were analyzed. A progressive increase in the number of Ig-secreting clones was observed and associated with a constant proportion (approximately 6%) of autoreactive B cell clones. However, dramatic changes in the pool of autoreactive B cell hybridomas were observed as the disease evolved, including the selective maintenance of IgM anti-DNA polyspecific antibodies, reduction in percentage of polyspecific IgM mAb with no DNA-binding activity, and the production of IgG anti-DNA antibodies of the IgG2 class. The kinetics, immunochemical properties, and idiotypic analysis of polyspecific IgM mAb with DNA-binding activity strongly suggest that they belong to natural Auto Ab and constitute the precursors of pathologic IgG anti-DNA antibodies. In addition, and IgM polyspecific antibody was demonstrated to bind IgG anti-DNA mAb through F(ab')2 interactions suggesting a regulatory role of natural antibodies and their participation in the control of pathologic Auto Ab production.

Age Factors↗
PubMed1992

Production of a human monoclonal anti-epithelial cell surface antibody derived from a patient with pemphigus vulgaris.

The production of monoclonal autoantibodies derived from individuals with autoimmune diseases constitutes a powerful tool to analyse an autoimmune process at both the antigen and antibody levels. We established a human anti-epithelial cell surface monoclonal antibody by applying hybridoma technology using peripheral blood lymphocytes from a patient with pemphigus vulgaris using a heteromyeloma as the fusion partner. The F12 monoclonal antibody displays four major characteristics: (1) it belongs to the IgM, kappa class; (2) it binds to the cell surface of stratified squamous and simple epithelia; (3) it recognizes an antigenic determinant associated with the desmosomal complex as demonstrated by indirect immunoelectron microscopy; (4) by immunoblotting analysis, it reacts with a 185 kDa polypeptide which was also recognized by a few pemphigus vulgaris sera. Although the F12 monoclonal antibody does not have the immunochemical properties of classical pemphigus vulgaris autoantibodies, several arguments suggest its relevance to the pemphigus vulgaris autoimmune response and, therefore, the heterogeneity of the antigen/antibody systems involved in this autoimmune disorder.

Adolescent↗
PubMed1992

Analysis of T cell receptors in rheumatoid arthritis: the increased expression of HLA-DR antigen on circulating gamma delta+ T cells is correlated with disease activity.

The phenotypic characteristics of peripheral blood T cells, isolated from 37 rheumatoid arthritis (RA) patients and 17 healthy controls were determined with special emphasis on gamma delta+ T cells and CD4-CD8- alpha beta+ T cells. Two- and three-colour automated flow cytometry analyses were performed using a panel of MoAbs directed against differentiation antigens and T cell receptor molecules. The results demonstrated: (i) no significant difference between the percentages of CD4-CD8- alpha beta+ T cells in patients and controls; (ii) a significant decrease of the gamma delta+ T cell level in the peripheral blood of RA patients relative to controls; (iii) phenotypic abnormalities of circulating gamma delta+ T cells in RA patients suggestive of an activation status in vivo. These abnormalities included a significant reduction in the density of the T cell differentiation antigen CD3 and an increase in the expression of HLA-DR antigen. The level of circulating HLA-DR+/gamma delta+ T cells was significantly higher in patients with active disease. HLA-DR+/gamma delta+ T cells were also present in the synovial fluid obtained from three patients with an active disease. In addition, preliminary experiments showed that the activated gamma delta+ T cells were predominantly V delta 1. Taken together, these data support the involvement of gamma delta+ T cells in the pathogenesis of RA.

Adult↗
PubMed1992

[Prevalence and description of cardiac involvements in primary antiphospholipid syndrome].

In order to assess the prevalence of cardiac involvement in the primary antiphospholipid syndrome (PAS), a syndrome which associates thromboembolism, recurrent abortion, the presence of antiphospholipid antibodies and thrombocytopenia, transthoracic (TTE) and trans-esophageal echocardiography (TEE) was performed in 15 patients, 10 women and 5 men with a mean age of 38.8 +/- 11 years, with the PAS but without systemic lupus erythematosus. The presentation of the PAS was a thrombotic event (6 arterial and 7 venous) in 13 cases, and recurrent abortion in 3 cases. Twelve patients had high anticardiolipin antibody levels (> or = 15 U GPL) and 12 had a raised anti-prothrombinase antibody title. Valvular heart disease was detected in 9 patients (60%) as a valve thickening (> or = 5 mm for the mitral and > or = 3 mm for the aortic valve) or nodule. Mitral regurgitation was observed in 4 cases both on TTE and TEE and was mild in 3 cases and severe in 1 case. Aortic regurgitation was diagnosed in 6 patients, in 3 cases by TTE and in 6 cases by TEE. It was mild in 5 cases and moderate in the other cases. Pericardial effusion was observed in 3 patients (20%), alone in 1 case and associated with valvular disease in the other two cases. No abnormality of left ventricular systolic or diastolic function could be demonstrated. In conclusion, cardiac involvement seems to be common in the PAS, and TEE is a sensitive and accurate method for describing the valvular, especially aortic valve, abnormalities.

Abortion, Habitual↗
PubMed1991

[Spontaneous rupture of subclavian artery disclosing Ehlers-Danlos disease. A case].

The authors report the case of a 30-year old man who suffered spontaneous rupture of the right subclavian artery. Treatment consisted of carotid-axillary graft since the fragility of the vessel precluded direct suture. The clinical symptoms, together with histological and ultrastructural examinations led to a diagnosis of Ehlers-Danlos syndrome with purely arterial manifestations.

Adult↗
PubMed1991

Immunogenicity and safety in newborns of a new recombinant hepatitis B vaccine containing the S and pre-S2 antigens.

A study to evaluate the safety and immunogenicity of a recombinant hepatitis B vaccine containing the S and pre-S2 antigens (GenHevac B Pasteur) was conducted in healthy newborn infants. All infants received 20 micrograms of vaccine within 24 h of birth and at 1 and 2 months with a booster injection at month 12. The vaccine was administered alone in 19 infants born to low risk mothers, i.e. surface antigen (HBsAg)-negative and antibody to the core antigen (Anti-HBc)-positive mothers. The vaccine was administered in combination with 100 IU hepatitis B immune globulin (HBIg) at birth and 1 month in 18 infants born to high risk mothers, i.e. HBsAg positive mothers. In the group not receiving HBIg, the anti-HBs seroconversion rate at the 10 mIU ml-1 threshold was 50% 1 month after the first injection. In both groups, the anti-HBs seroconversion rates were 100% 1 month after the third injection and greater than 85% 1 month after the second injection. After the booster injection greater than 90% of the infants had an anti-HBs titre greater than 1000 mIU ml-1 which will probably provide them with adequate protection for several years. The kinetics of the anti-pre-S2 response was similar to that of the anti-HBs response and 100% of infants in both groups had seroconverted 1 month after the second injection of the vaccine. The side effects were scarce, all mild and transient.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Differentiation↗
PubMed1991

Anti-myeloperoxidase antibodies: immunological characteristics and clinical associations.

Antibodies directed against myeloperoxidase (anti-MPO) were detected, using a solid-phase ELISA and purified sputum myeloperoxidase as the substrate, in 54 sera from 22 patients. Anti-MPO were present in 17 patients with crescentic glomerulonephritis (CGN), Wegener's granulomatosis (WG) and microscopic polyarteritis (MPA), and thus are associated with different forms of vasculitis. Anti-MPO were also present in five out of 20 patients with systemic lupus erythematosus (SLE). Anti-MPO activity in SLE sera was low, in contrast to the high titers observed in patients with vasculitis. All positive sera had IgG anti-MPO (except two SLE sera) and most of them also contained low-titered IgM anti-MPO. Only three patients had high IgM anti-MPO activities, the significance of which remains to be determined. In patients with CGN, WG or MPA, the anti-MPO titer decreased following therapy and paralleled the disease activity. Thus, anti-MPO constitute a useful diagnostic tool and a sensitive marker of disease activity in this group of patients with vasculitis.

Arteritis↗
PubMed1991

[Immunogenicity and harmlessness in the newborn of a vaccine (GenHevac B) containing the antigens S and pre-S2].

A study to evaluate the safety and immunogenicity of a recombinant hepatitis B vaccine containing the S and pre-S2 antigens (GenHevac B Pasteur) was conducted in healthy newborn infants. All infants received 20 micrograms of vaccine within 24 hours after birth, at 1 and 2 months with a booster injection at month 12. The vaccine was administered alone in 19 infants born to low risk mothers, i.e. surface antigen (HBsAg)-negative and antibody to the core antigen (Anti-HBc)-positive mothers. The vaccine was administered in combination with 100 IU hepatitis B immune globulin (HBIg) at birth and one month in 18 infants born to high risk mothers, i.e. HBsAg positive mothers. In the group not receiving HBIg, the anti-HBs seroconversion rate at the 10 mlU/ml threshold was 50% one month after the first injection. In both groups, the anti-HBs seroconversion rates were 100% one month after the third injection and above 85% one month after the second injection. After booster injection, more than 90% of the infants had an anti-HBs titre above 1,000 mlU/ml that will probably provide them with adequate protection for several years. The kinetics of the anti-pre-S2 response was similar to those of the anti-HBs response and 100% infants in both groups had seroconverted one month after the second injection of the vaccine. The side effects were scarce, all mild and transient. Given the protective role of the anti-pre-S2 antibodies, the precocity of the response to pre-S2 antigen may therefore increase the effectiveness of hepatitis vaccination.(ABSTRACT TRUNCATED AT 250 WORDS)

Female↗
PubMed1991

[Significance of isolated anti-HBs antibodies in subjects not vaccinated against hepatitis B viruses].

The significance of isolated anti-HBs antibodies in subjects not vaccinated against the hepatitis B virus (HBV) was investigated in 13 healthy blood donors. All were European and none had any risk factor for hepatitis B infection. Serological assays included HBV-DNA and anti-preS 2 antibody determinations which were all negative. After injection with hepatitis B vaccine (Hevac B), only one out of the 13 subjects exhibited an anamnestic response in favor of secondary immunization. Neutralization tests for serum anti-HBs antibody were positive in only 6 subjects. Our data suggest that in most cases isolated anti-HBs positivity does not correspond to true antibody; booster injection of HBV vaccine seems to be the best way of verifying that antibodies are really protective.

Adult↗
PubMed1990

[Lupus erythematosus disseminatus, lesional mechanisms, pathogenesis and genetics].

Systemic lupus erythematosus (SLE) is a model of autoimmune disease. Its study, and that of spontaneous murine models, have benefited from new immunological and molecular biology techniques. New hypotheses have been put forward to explain the mechanisms of SLE lesions. The genetic origin of autoantibodies begins to be better known. Auxiliary CD4+ lymphocytes seem to play a capital role in the occurrence of lymphocyte abnormalities. The disease is multigenic. Much work is currently devoted to the identification and characterization of genetic factors.

Autoantibodies↗
PubMed1990

[Contribution of murine models of spontaneous lupus to the analysis of genetic factors in human disease].

Genetic factors contribute to the expression of human systemic lupus erythematosus (SLE): they appear to be complex and are difficult to study in man. Most advances have been made as a result of studies of spontaneous murine models of SLE, either by conventional genetics or molecular biology. The former demonstrated that no single or simple genetic explanation of the disease is likely and that the immune manifestations are multigenic. Molecular biology techniques suggest that disease-associated genes probably lie within the major histocompatibility complex (MHC) of NZW mice and seem to be genes coding for MHC class II antigens. Such an analysis of genes encoding elements involved in immune system functions (e.g., immunoglobulins, T cell antigen and MHC antigen receptors) provides valuable information concerning the role(s) of genetic factors leading to SLE.

Animals↗
PubMed1989

The VH gene sequences of anti-DNA antibodies in two different strains of lupus-prone mice are highly related.

The heavy and light chain V region sequences of an IgG anti-DNA autoantibody (PME77), derived from a lupus-prone (NZB x NZW)F1 mouse have been determined by mRNA sequencing. The V kappa gene segment belongs to the V kappa 1A gene sub-group and is found in several (NZB x NZW)F1 and MRL lpr/lpr anti-DNA antibodies, as well as in other antibodies of unrelated specificities. The VH gene segment appears to represent a unique gene or a subfamily of the large J558 VH gene family of the mouse, and is highly related to a germ-line sequence of a major anti-DNA idiotype (H130, IgM) of MRL mice. This anti-DNA-related VH segment has not been found, so far, to be expressed in antibodies with specificities for external or synthetic antigens; therefore, expression of such specificities may be regulated by powerful mechanisms of self tolerance in the healthy animal. In addition, both the heavy and light chain of the PME77 IgG antibody were found to contain somatic point mutations with a high ratio of replacement to silent mutations in complementarity determining regions. This IgM to IgG sequence relationship suggests an affinity maturation process, which is driven by the autoantigen.

Amino Acid Sequence↗
PubMed1989

Randomized dose range study of a recombinant hepatitis B vaccine produced in mammalian cells and containing the S and PreS2 sequences.

The safety and immunogenicity of different doses (2, 5, 10, and 20 micrograms of a recombinant hepatitis B virus (rHBV) vaccine containing the S and PreS2 sequences and produced in mammalian cells were compared to those of a plasma-derived hepatitis B virus vaccine (Hevac B Pasteur) in 482 volunteers. Local and general side effects were mild and transient. No transaminase level elevation and autoantibody production were observed. The antibody to hepatitis B surface antigen (HBsAg) seroconversion rates did not differ in the groups receiving the rHBV vaccine and the subjects receiving the plasma-derived vaccine. Both vaccines elicited levels of antibodies to HBsAg in greater than 90% of the participants. Geometric mean titers of antibodies to HBsAg induced by the 10- and 20-micrograms doses of the rHBV vaccine did not differ from that induced by the plasma-derived vaccine and were higher than those induced by the 2- and 5-micrograms rHBV vaccine doses. The striking feature of the rHBV vaccine compared to the plasma-derived vaccine was an early and high production of antibodies to PreS2, which may constitute an advantage in prevention of hepatitis B virus infection.

Adolescent↗
PubMed1988

[Immunogenicity of a hepatitis B vaccine obtained by genetic recombination and containing products of S and pre-S2 genes].

Immunization against hepatitis B by means of a vaccine obtained by genetic recombination on chinese hamster ovary cells was attempted in 32 adult subjects. The HBs antigen was purified from the culture supernatant and contained S and pre S2 genes products. Three 20 micrograms doses were injected intramuscularly at intervals of one month. Anti-HBs seroconversion levels and the geometrical mean of antibodies were slightly higher than those observed with plasma vaccines or genetically engineered yeast-derived vaccine. Antibodies directed against HBs appeared more rapidly and at a higher titre. Anti-pre S2 antibodies were detected after the third injection in 84 per cent of the subjects vaccinated. This recombinant hepatitis B vaccine prepared from chinese hamster ovary cells will probably be as effective as the first generation vaccines obtained by purifying the HBs antigen obtained from the blood of asymptomatic carriers.

Adult↗