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J Hébert

Publications and source records attributed to J Hébert.

At least 19 recordsLinked to original sources
PubMed1995

Inversion-associated translocations in acute myelomonocytic leukemia with eosinophilia.

Cytogenetic studies of three acute myelomonocytic leukemias with bone marrow eosinophilia (M4EO) revealed chromosome 16 inversion associated with additional abnormalities. The inverted chromosome 16 was involved in two patients. Fluorescence in situ hybridization (FISH) experiments with a YAC probe detecting inv(16) showed that the translocation breakpoints involving chromosome 16 did not implicate the inversion breakpoints. FISH can thus distinguish between true variant translocations and translocations with other breakpoints on chromosome 16 in M4EO.

Adult↗
PubMed1995

Lol p I-specific IgE and IgG synthesis by peripheral blood mononuclear cells from atopic subjects in SCID mice.

BACKGROUND: The development of an animal model representative of the in vivo situation of human atopic diseases is always of interest for a better understanding of IgE production and regulation. Along these lines, mice with severe combined immunodeficiency (SCID mice) engrafted with lymphocytes from atopic subjects might be a suitable model for such studies. OBJECTIVE: This study aims to analyze the production of Lol p I-specific IgE and IgG antibodies in SCID mice after transplantation of human peripheral blood mononuclear cells from atopic patients sensitive to grass pollens and from nonatopic donors. METHODS: Peripheral blood mononuclear cells were transplanted into SCID mice, which were then challenged with Lol p I, and antibody responses (IgG and IgE) were analyzed over a 6-week period. RESULTS: Total IgG antibody was measured in each mouse serum after transplantation. Also, most mice (regardless of whether donors were atopic) that were challenged with Lol p I produced specific IgG antibody. Total IgE antibody production was observed only in mice grafted with cells from atopic patients. Lol p I-specific IgE antibodies were also produced after immunization with Lol p I. Although IgG antibody/response tended to plateau, the IgE antibody response increased until it peaked and declined thereafter. Interferon-gamma was detected in sera from mice producing IgE antibody, which supports a possible role of interferon-gamma in the decrease of IgE response. CONCLUSION: This study suggests that the SCID mouse model could represent an interesting approach to studying specific, total IgG and IgE antibody production, and ultimately their regulation.

Allergens↗
PubMed1995

A natural mutation of the amino acid residue at position 60 destroys staphylococcal enterotoxin A murine T-cell mitogenicity.

A variety of techniques have been used to identify the amino acid residues of bacterial superantigens involved in their interactions with major histocompatibility complex (MHC) class II and T-cell receptor (TCR). In this study, we isolated a naturally mutated staphylococcal enterotoxin A (SEA) from three different Staphylococcus aureus strains, in which the amino acid at position 60 has been changed from aspartic acid (D) to asparagine (N). We then studied the influence of this change on the immunological activities of SEA. Our results demonstrated that this mutation does not affect the capacity of SEA to bind MHC class II molecules and consequently activates human monocytes and peripheral blood lymphocytes. In contrast, mutated SEA failed to stimulate the proliferation of murine splenic lymphocytes of two different strains, and when presented by human MHC class II molecules, it also failed to activate murine cell line 3DT, which expresses the SEA-specific TCR V beta element (V beta 1). These results indicate that this mutation alters the interaction between SEA and murine TCR. The reactivity patterns of the mutated SEA with two specific anti-SEA monoclonal antibodies suggested that the observed effect of the isolated mutation in the murine system might be due to certain conformational changes in the SEA molecule introduced upon changing the D at position 60 to N. Site-directed mutagenesis of the N residue to D or to glycine reconstituted the ability of SEA to stimulate murine splenic lymphocytes. The different effects of this natural mutation at position 60 on the immunological activities of SEA with murine and human cells highlight the relevance of the affinity and avidity in SEA-TCR interactions in the function of different species or may reflect a difference in epitope specificity.

Animals↗
PubMed1994

Possible dual role of anti-idiotypic antibodies in combined passive and active immunotherapy in honeybee sting allergy.

BACKGROUND: Passive infusion of beekeepers' plasma was shown to protect patients against systemic reactions occurring during active immunotherapy by mechanisms still to be clarified. It is tempting to speculate that anti-idiotypic antibodies could play a role because they are found in beekeepers' plasma and are involved in the regulation of IgE synthesis. METHODS: In this report we studied the effects of passive infusion of a beekeeper's plasma rich in anti-idiotypic antibodies to a patient who experienced systemic reactions to honeybee venom. RESULTS: We reported, during the days after the infusion, a decrease of clinical sensitivity to the honeybee venom. Indeed, the patient tolerated a cumulative dose of 280 micrograms of venom without adverse reactions. We also observed decreases in skin mast cell and in basophil sensitivity. After the plasma infusion, a modified rush immunotherapy with honeybee venom was initiated in our patient. In the following 76 weeks, increased levels of anti-idiotypic antibodies in the serum of the patient were associated with a diminution of specific antibodies (IgG and IgE) to honeybee venom. CONCLUSION: These results suggest a dual role of anti-id in our combined protocol of passive and active immunotherapy: an immediate action on clinical sensitivity along with a decrease of skin mast cell and basophil sensitivity and an immunoregulatory role on specific antibody production.

Adult↗
PubMed1994

Determination of neutralizing epitopes in variable domains I and IV of the major outer-membrane protein from Chlamydia trachomatis serovar K.

Chlamydia trachomatis is a leading cause of sexually transmitted diseases and a number of strategies have been developed to produce vaccines to prevent its transmission. The purpose of this study was to map the neutralizing epitopes of C. trachomatis major outer-membrane protein (MOMP) serovar K by using anti-MOMP antibodies and synthetic peptides. Seven anti-MOMP monoclonal antibodies and three polyclonal antisera were produced and characterized. Their fine specificity was defined by direct binding assay on 15 peptides of 10 amino acid residues, overlapping by five residues, corresponding to the four variable domains (VDI-VDIV: residues 64-85, 139-160, 224-237 and 287-319) of MOMP serovar K. Our data confirmed that a neutralizing epitope is found in VDIV, defined by peptides K12 and K13. This epitope is 296TTLNPTIAG304, which has never been reported as a neutralizing epitope of serovar K. Another neutralizing epitope, defined by peptide K2, has been identified in VDI. This epitope is in the same position as 71VAGLEK76, a peptide with neutralizing activity found in serovar A, but they are not identical because antibodies against peptide K2 do not bind to this epitope. No neutralizing epitope was found in the two other variable domains (VDII and III). In summary, two neutralizing sites, one in variable domain I and one in variable domain IV, were identified in serovar K.

Amino Acid Sequence↗
PubMed1994

Modulation of immune response to Lol p I by pretreatment with anti-idiotypic antibody is not restricted to the idiotypic expression.

To study the role of anti-idiotypic antibodies in the regulation of the immune response to Lol p I (the major allergenic component of rye grass pollen), we have recently generated a panel of three MoAbs directed against distinct epitopes of Lolp I and an anti-idiotypic MoAb directed against the idiotype borne by one of the anti-Lol p I MoAbs (290A-167). The effects of pretreatment with this anti-idiotypic MoAb in BALB/c mice before immunization with the antigen have been examined. The anti-idiotypic MoAb or unrelated MoAb were given weekly for 8 weeks intraperitoneally. Mice then received the antigen (2 micrograms) adsorbed with alum (2 mg) at weeks 9, 11 and 13. Serum anti-Lol p I antibodies (IgG or IgE) and specific idiotypic responses were measured. Anti-Lol p I IgG antibodies could be detected before immunization with Lol p I only in mice pretreated with anti-idiotypic MoAb. Immunization with Lol p I induced an anti-Lol p I IgG response in both groups, but this response was higher in mice that received anti-idiotypic MoAb. Similar profiles were seen for specific IgE antibodies and idiotypic responses. Surprisingly, idiotypes borne by other anti-Lol p I MoAbs (539A-6 and 348A-6) had also been enhanced after pretreatment with the anti-290A-167 MoAb. These observations suggested that the pretreatment with this anti-idiotypic MoAb modulates not only the expression of the respective idiotype, but also affects other idiotype responses.

Allergens↗
PubMed1994

Mimicry of a neutralizing epitope of the major outer membrane protein of Chlamydia trachomatis by anti-idiotypic antibodies.

The major outer membrane protein (MOMP) is a primary target antigen for the development of chlamydial vaccine. This protein is composed of four variable domains (I to IV) flanked by constant regions. Some of the variable domains contain antigenic determinants that elicit a neutralizing antibody response. Murine monoclonal antibodies (MAbs) against three nonoverlapping epitopes of MOMP were developed. One of these, called DP10, bound to all serovars, as shown by immunoblot analysis, and neutralized chlamydial infectivity for hamster kidney (HaK) cells in a complement-independent in vitro assay. Furthermore, analysis of the fine specificity of this MAb showed that it recognized a synthetic peptide contained within variable domain IV of the MOMP. Anti-idiotypic antibodies (aId) directed against this anti-MOMP MAb were produced in rabbits. These aId specifically bound to the relevant idiotype (DP10) and inhibited the binding of anti-MOMP MAb (DP10) to MOMP preparations in a dose-dependent fashion. The specificity of our aId for the binding site of anti-MOMP MAb is further suggested by the binding inhibition of affinity-purified aId to DP10 by the synthetic peptide defined by the idiotype. In addition, these aId also reacted with anti-MOMP antisera from rats and mice, suggesting an idiotypic cross-reactivity between these species. Finally, immunization of naive mice with aId induced an antibody response directed against the peptide defined by our anti-MOMP MAb and with neutralizing activity. Taken together, these data suggest that aId mimic a neutralization site on MOMP and could serve as a surrogate antigen to induce protective immunity against Chlamydia trachomatis.

Amino Acid Sequence↗
PubMed1993

Idiotype and anti-anti-idiotype antibodies to Neisseria gonorrhoeae lipooligosaccharides with bactericidal activity but no cross-reactivity with red blood cell antigens.

A panel of murine mAb against three different epitopes of Neisseria gonorrhoeae lipooligosaccharides (LOS) was developed. Only one of these, 3G5, displays bactericidal activity against all in vitro serum-resistant strains of N. gonorrhoeae. Evidence suggests that sialylation, which could occur in vivo, modifies some LOS epitopes in such a way that the strains become resistant to bactericidal activity and are no longer recognized by specific antibodies. The epitope recognized by our bactericidal mAb is not affected by sialylation as shown by immunoblot analysis. We also provided evidence that the 3G5 epitope is different from RBC precursor Ag, since our mAb did not induce RBC agglutination. Since LOS induce an immune response in a T cell-independent fashion and are highly toxic, they cannot be used for immunization. Use of anti-idiotypic antibodies (aId) could be a way to bypass these difficulties. Therefore, in the present study, aId were produced in rabbits and rendered idiotype-specific by appropriate adsorption. These aId specifically bind to the relevant Id but not to LOS, and inhibit only the binding of anti-LOS mAb (3G5) to LOS preparations from N. gonorrhoeae in a dose-response fashion. The specificity of our aId for the binding site of anti-LOS mAb is suggested by the binding inhibition of affinity-purified aId to Id by LOS. In addition, the capacity of aId to inhibit bactericidal activity of this anti-LOS mAb and the idiotypic cross-reactivity between rat and mouse anti-LOS antibodies support this point. Finally, the elicitation of anti-LOS activity with bactericidal activity upon immunization of naive mice with aId confirms the internal image properties of the aId. These data suggest that a bactericidal mAb suitable for immunoprotection was obtained, and the production of aId opens the door for development of a vaccine.

Animals↗
PubMed1993

HRF of 30 kDa: evidence for active synthesis.

A variety of mediators are involved in the pathophysiology of a number of clinical conditions. Among them histamine-releasing factors (HRF) act as secretagogue for basophils and mast cells to cause cell degranulation and histamine release. Studies on the kinetics of HRF production by activated mononuclear cells (MNC) have suggested an active synthesis of this cytokine. Using a [35S]-metabolic cell labeling method, we first analyzed the capacity of MNC from patients with allergic rhinitis to ragweed to actively synthesize HRF. We then found that stimulation of MNC with allergen promoted a synthesis of large quantities of proteins, including a protein of about 30 kDa. Secondly, we developed a method for the enrichment of HRF molecules from crude supernatants of ragweed-stimulated MNC using ion exchange and gel filtration chromatography. We observed that the yield of HRF activity is seen just before the chymotrypsinogen marker. The estimated molecular weight was 30-35 kDa.

Basophils↗
PubMed1993

Chronic idiopathic urticaria: possible contribution of histamine-releasing factor to pathogenesis.

BACKGROUND: Histamine-releasing factor was recently shown to be clinically relevant in allergic rhinitis and asthma. HRF could also be involved in the pathogenicity of chronic idiopathic urticaria (CU). The purpose of this study was to investigate the role of HRF in the pathophysiology of CU. METHODS: Blisters were induced on lesional and nonlesional skin of 12 patients with CU and on normal skin of five control subjects. HRF activity and histamine content were measured in all samples recovered from each skin site. RESULTS: Significantly more HRF was found in blister fluids from lesional skin of patients with CU as compared with nonlesional skin and skin of control subjects. In addition, histamine content in blister fluids from affected skin of patients with CU was significantly higher in comparison with both nonlesional skin of patients with CU and skin of control subjects. HRF activity was also higher in blister fluids from nonlesional skin of patients with CU than that of control subjects, in spite of equivalent histamine content. CONCLUSION: These data suggest that the inflammatory reaction found in CU disease is associated with the cutaneous release of HRF.

Adult↗
PubMed1993

Biological activity of monoclonal anti-idiotypic antibody representing the internal image of the major allergenic component of Lolium perenne pollen.

Upon immunization with an anti-Lol p I (major allergenic component of Lolium perenne pollen) monoclonal antibody, we have previously produced anti-idiotypic monoclonal antibody (A7H2) displaying some internal image properties. The present study was designated to evaluate the capacity of this anti-idiotypic monoclonal antibody to mimic functionally the antigen by triggering histamine release from basophils of patients allergic to Lol p I. Anti-idiotypic monoclonal antibody, as the antigen, could induce histamine release in a dose-response fashion in all of the atopic patients (6/6). The inhibition of this histamine release by the addition of the idiotype (290A-167) confirmed the specificity of the reaction. Binding inhibition of human IgE to Lol p I demonstrated that the anti-idiotypic antibody recognized an idiotope expressed in the antigen-combining site of IgE molecules. Altogether, these data confirmed the internal properties of our anti-idiotypic antibody and it can mimic the original antigen in its capacity to trigger histamine release.

Adult↗
PubMed1992

Chronic idiopathic urticaria: profiles of skin mast cell histamine release during active disease and remission.

Chronic idiopathic urticaria (CIU) is characterized by the increased releasability of histamine by mast cells in normal-appearing skin. In active CIU, this abnormality is consistently present. To determine if this finding subsides when the disease goes into remission phase, we analyzed the histamine secretion in patients with CIU in remission (CIUR) compared with that of patients with CIU and in normal control (NC) subjects, with the skin-chamber technique. The profiles of histamine release in sites challenged with compound 48/80 were significantly different in the groups with CIU and CIUR. Furthermore, patients with CIUR did not differ from NC subjects in terms of histamine releasability under compound 48/80 stimulation (p greater than 0.1). These data suggest that the state of excessive skin mast cell sensitivity is a reversible and transient phenomenon in CIU disease.

Analysis of Variance↗
PubMed1992

Allergic rhinitis to ragweed pollen. I. Reassessment of the effects of immunotherapy on cellular and humoral responses.

This work presents a double-blind, placebo-controlled study of 27 patients with allergic rhinitis to ragweed who received preseasonal desensitization immunotherapy [IT] with alum-precipitated aqueous ragweed extracts. We reassessed the following parameters in relation to clinical responses: clinical scores, nasal reactivity to a provocative dose of ragweed causing a 75% fall in airflow rate (PD75), ragweed IgE and IgG, and ragweed-induced basophil histamine release (BHR). First, the nasal PD75 correlated with the severity of nasal symptoms (p less than 0.05). Second, we confirmed a significant symptomatic improvement in the IT-treated group either by clinical scores (p less than 0.05) or the prevention of the seasonal fall of the PD75 (p less than 0.005). Also, IT reduced the seasonal rise of IgE (p less than 0.02) and induced an increase in IgG (p less than 0.01) and a decrease in BHR (p less than 0.03). There was a significant correlation between IgE and BHR (r = 0.80; p less than 0.01). After selecting out the effects of IgE, the BHR was still higher in the placebo-treated group than in the IT-treated group (p less than 0.02), suggesting the involvement of other modulating factors. Symptomatic improvement after IT correlated only with the summation of both IgE and BHR (PD75; r = 0.64; p less than 0.005). This observation suggests that the severity of clinical symptoms is determined by several interacting factors and not by the antibody response alone.

Adult↗
PubMed1992

Allergic rhinitis to ragweed pollen. II. Modulation of histamine-releasing factor production by specific immunotherapy.

A number of cytokines, including histamine-releasing factors (HRFs), have a role to play in IgE-mediated asthma. However, the influence of HRF in allergic rhinitis without asthma remains to be revealed. This article presents a double-blind, placebo-controlled study on the role of HRF in ragweed-allergic rhinitis and its modulation by natural pollen exposure and specific immunotherapy (IT). Twenty-seven patients allergic to ragweed were randomly assigned to receive either preseasonal alum-precipitated aqueous extracts of ragweed or placebo. Before the onset of therapy and during the ragweed-pollen season, subjects were evaluated for each of the following: clinical scores, ragweed IgE and IgG antibody levels, and spontaneous and allergen-driven HRF production. Thirteen nonatopic volunteers were also studied in the same protocol. First, before the initiation of therapy, more HRF was produced by both unstimulated and ragweed-stimulated mononuclear cells (MNCs) of atopic subjects as compared to MNCs of nonatopic subjects. Second, MNCs of the placebo-treated group produced significantly more spontaneous and ragweed-specific HRF during the pollen season compared to the preseasonal values. Finally, specific IT not only improved the clinical manifestation of allergy but also prevented the seasonal rise of spontaneous and ragweed-driven HRF production, along with a well-known change in other immunologic parameters associated with successful IT.

Adult↗
PubMed1992

Increase in T3 levels during hypocorticism in patients with chronic secondary adrenocortical insufficiency.

The clinical and biochemical manifestations of secondary adrenocortical insufficiency are not well defined in the medical literature. This study was designed to determine the clinical and laboratory features suggesting the diagnosis of adrenal insufficiency in 15 chronic ACTH deficiency patients during low and normal cortisol states. Except for fatigue and weakness, the characteristic clinical manifestations of primary adrenal insufficiency occurred rarely. ACTH deficiency did not significantly modify blood glucose, serum calcium, sodium, potassium and differential white blood cell count. However, serum T4 was lower (65 +/- 19 vs 95 +/- 21 nmol/l, p less than 0.001) during cortisol deficiency, while T3 was higher (2.4 +/- 0.67 vs 2.0 +/- 0.60 nmol/l, p less than 0.001). Furthermore, rT3 decreased significantly during hypocorticism (0.27 +/- 0.07 vs 0.18 +/- 0.07 nmol/l, p less than 0.001). The T4/T3 ratio was significantly lower than the normal in 15 out of the 17 episodes of ACTH deficiency (29 +/- 12.5 vs 57 +/- 9.4, p less than 0.0001). We conclude that the increase in T3 and decrease in T4 levels are associated with chronic secondary adrenocortical insufficiency. This laboratory feature could be due, at least in part, to the increased peripheral conversion of T4 to T3 during cortisol deficiency.

Adrenal Cortex Diseases↗
PubMed1991

Reversible hypertriiodothyroninaemia due to adrenal insufficiency.

It is well known that an excess of glucocorticoids affects thyroid tests. The effect of adrenal deficiency on thyroid hormones is less well defined. We here describe the case of a 33-year-old woman with Cushing's disease who was cured by trans-sphenoidal surgery. During the postoperative period, a secondary adrenal insufficiency developed. The thyroid blood tests then revealed elevated L-triiodothyronine (T3) levels and a decrease in reverse T3. These findings suggest that secondary adrenal deficiency may be associated with high T3 levels, which may be due to an increase in the peripheral conversion of thyroxine (T4) to T3.

Adrenal Insufficiency↗
PubMed1990

Generation of anti-idiotypic and anti-anti-idiotypic monoclonal antibodies in the same fusion. Support of Jerne's Network Theory.

Upon immunization of mice with a mAb (290A-167) directed against an epitope of Lol p I (the major allergenic determinant of Lolium perenne), both anti-idiotypic (aId) mAb (Ab2) and anti-aId mAb (Ab3) were produced. The Ab2 displayed the following internal image properties of Lol p I: it can be affinity-purified on an immobilized Id column; its binding to the anti-Lol p I mAb (290A-167) is inhibited by Lol p I; it inhibits in a dose-response fashion the binding of the specific Id to Ag. It is recognized by anti-Lol p I antisera from different species such as mouse, human, and goat. The Ab3 which binds to Lol p I was also produced from the same fusion. This binding was inhibited significantly by aId mAb (Ab2), anti-Lol p I mAb (290A-167) and Lol p I. These data indicate that the two mAb with specificity for Lol p I (290A-167 and Ab3) share similar reactivity to the Ag and that aId mAb is the internal image of the epitope recognized by the Id. We showed also that the capacity of rabbit aId Ab directed against the 290A-167 Id to inhibit the binding of Ab1 and Ab3 to Ag was almost abolished by passage over a Ab3-coated Sepharose column. This would suggest that not only are the two mAb with reactivity to Lol p I (Ab1 and Ab3) directed against identical epitopes, but that they in fact shared identical idiotopes as well. The production of identical mAb upon immunization with either the Ag or the aId mAb supports that the conceptual framework proposed by Jerne finds its biologic application in the course of an immune response.

Animals↗