Search PubMed⌕ Search

Biomedical subjects

G C Faure

Publications and source records attributed to G C Faure.

At least 55 records · Page 3Linked to original sources

From Peyer's patches to tonsils. Specific stimulation with ribosomal immunotherapy.

Ribosomal immunotherapy has been successfully used since the 1960s to boost the immune system and provide protection against microbial infections. We have investigated both whether and how these immunostimulants behave as natural immunogens in the mucosa-associated immune system. According to current understanding of the physiology of the mucosal immune response, intestinal Peyer's patches and the related solitary nodules are the primary inductive sites involved in the immune protection of all mucosal surfaces. Sensitised lymphocytes generated at these sites reach the general circulation through lymphatic drainage and relocate in mucosal areas by means of specialised 'high endothelial venules'. We hypothesised that orally administered ribosomal preparations would yield sensitised B cells specific for bacterial antigens from the parent strains. These cells should then be detectable in the peripheral blood after ribosomal intake, and identifiable as plasma cells in mucosae-associated tissues after completing their terminal differentiation. Ultimately, specific IgA should appear in secretions. To this end, we studied the immune responses generated in children and adults after 'Ribomunyl' administration, according to various consecutive protocols. The initial hypothesis was confirmed by the identification of specific B cells in the peripheral blood, plasma cells in the tonsillar tissue and specific IgA in the saliva. An animal model involving the use of twin sheep enabled detection of the specific cells in mesenteric and cervical lymph nodes. Analysis of these data indicates that ribosomal preparations trigger the production of lymphocytes specific for both ribosomes themselves and whole bacterial antigens. This supports the fact that small antigenic motifs are carried as partly synthesised peptides on the ribosomal particles. Therefore, ribosomes boost an array of B cells that are specific for many antigenic determinants of the bacteria from which they are extracted. We were also able to show that the stimulation provided was specific, since no response to other bacteria could be detected. Finally, analysis of the kinetics of this stimulation confirmed that oral immunisation generates rapid and transient secretory responses, building increased numbers of memory cells that are readily available to respond to further challenges by either more ribosomal preparations or potential pathogens.

Adjuvants, Immunologic↗

Role of delayed cellular hypersensitivity and adhesion molecules in amoxicillin-induced morbilliform rashes.

BACKGROUND: Morbilliform rashes induced by amoxicillin are though to be caused by a delayed cell-mediated immune reaction. The importance of amoxicillin skin tests is not well defined. A better understanding of the mechanisms of amoxicillin-induced morbilliform rashes can be obtained by performing cutaneous immunohistological studies on specimens from amoxicillin-induced morbilliform rashes and positive amoxicillin skin test results. OBSERVATIONS: Skin biopsy specimens were obtained from 5 patients who had developed an amoxicillin-induced morbilliform rash. All patients underwent amoxicillin prick, patch, and intradermal tests. Similar immunohistological investigations were performed on amoxicillin-induced morbilliform rashes and positive skin test biopsy specimens, with a special focus on the expression of adhesion molecules. Three of the 5 patients developed delayed positive results to intradermal and patch tests and 2 patients developed delayed positive results to prick tests. Amoxicillin-induced morbilliform rashes were well reproduced by skin tests, with similar immunohistological results in amoxicillin-induced morbilliform rashes and skin test biopsy specimens. Keratinocytes were activated and expressed CD54 (intercellular adhesion molecule 1); perivascular lymphocytes were mostly CD2+, CD3+, and CD4+ and exhibited CD11a through CD18 (leukocyte function-associated antigen 1) and often HLA-DR and/or CD62L (leukocyte endothelial cell adhesion molecule 1); and endothelial cells were activated with a strong expression of CD54 (intercellular adhesion molecule 1), CD62E (endothelial leukocyte adhesion molecule 1), and CD31 (platelet endothelial cell adhesion molecule 1) in lesser amounts. CONCLUSIONS: Findings of this clinical and immunohistochemical study support the theory of a T-cell-mediated immune reaction in patients with amoxicillin-induced morbilliform rashes, with a strong involvement of adhesion molecules both on endothelial and infiltrating cells. Our findings emphasize the importance of delayed readings of amoxicillin prick, intradermal, and patch tests.

Amoxicillin↗

Specific humoral immune responses in 12 cases of food sensitization to sesame seed.

BACKGROUND: Hypersensitivity to sesame seeds is becoming increasingly frequent, probably owing to the larger use of this compound in international food. OBJECTIVES: This study investigated serum responses of 12 sesame sensitized patients (seven with food allergy, five with food sensitization), to a sesame protein extract, and attempted at identifying sesame major antigens. METHODS: Sesame protein extracts were prepared from black, white and brown sesame seeds. Electrophoretic analysis showed similar protein patterns in the three extracts, and proper preservation of the proteins integrity. The brown sesame extract was used to set-up an ELISA assay and measure serum levels of antisesame IgG, IgA, IgM and IgE in 12 samples from sesame-sensitized individuals and six controls. It also allowed to perform western blot analyses in order to investigate the molecular weight of sesame proteins recognized by IgG, IgA and IgE. RESULTS: Nineteen protein bands were observed upon polyacrylamide gel electrophoresis of the sesame protein extracts. Using this whole extract in ELISA, significant antisesame IgG, IgA and IgE-responses were observed in the serum of sensitized individuals, different from the lower signals obtained with control samples. Western blot analysis demonstrated highly polymorphic IgG and IgA responses and a more restricted IgE response pattern, suggesting that two proteins, respectively, 14 kDa and 25 kDa are mostly involved in sesame IgE-dependent hypersensitivity, the 25 kDa band presenting several characteristics of a major allergen. CONCLUSIONS: This study reports novel information on the possible involvement of a 25 kDa sesame protein in IgE-dependent hypersensitivity to sesame seeds.

Adult↗

Comparative assessment of phospholipid-binding antibodies indicates limited overlapping.

The implication of autoantibodies with anticoagulant and/or so-called antiphospholipid activities, under clinical circumstances with vascular obliteration, has led to the development of various types of tests allowing their detection. The most used tests involve investigation of the presence of an anticoagulant effect and of anticardiolipin IgG. It has also been proposed that the reactivity of patient samples toward other phospholipids or proteins be tested, but it remains difficult to appreciate which tests are redundant or complementary. Here we investigated whether the dissociation or association of anticoagulant and anticardiolipin correlated with specific ELISA reactivity to five other phospholipids: phosphatidylserine, phosphatidylinositol, phosphatidic acid, phosphatidylcholine, and phosphatidylethanolamine. The study was performed with 70 samples, evenly partitioned as positive for either anticardiolipin antibodies or anticoagulant effect, or both. Our data clearly confirm that cardiolipin reactivity is an individual entity, likely to be complementary to other assays. Neither anticardiolipin nor anticoagulant levels correlated with assays investigating antibody levels toward the five other phospholipids, although higher mean levels were noted when both lupus anticoagulant and anticardiolipin antibodies are present. Individual patterns were evidenced in all groups. These data support the interest of current and further studies exploring the clinical relevance of individual reactivities to phospholipids.

Adolescent↗

Investigation of activation markers demonstrates significant overexpression of the secretory component on salivary glands epithelial cells in Sjögren's syndrome.

Labial salivary glands biopsies (LSG) performed to support clinical anomalies suggestive of Sjögren's syndrome (SS) sometimes fail to confirm the diagnosis. Here we investigated whether epithelial activation markers could provide further information. Frozen cut sections of LSG from 40 patients, including 23 confirmed SS, were examined in immunofluorescence for the expression of HLA class II molecules, the protector of apoptosis bcl-2, the intercellular adhesion molecule 1 (ICAM-1) and secretory component (SC). Class II molecules were highly expressed on epithelial cells in SS patients (DR > DP > DQ). Bcl2 was expressed in infiltrating cells which were more numerous in the group of SS patients. ICAM-1 was present on endothelial and infiltrating cells of a few patients in both groups. Epithelial cells produced SC in 83% of SS patients samples vs four cases of non-SS patients (P = 0.0002). Investigation of the expression of SC on glandular epithelial cells could therefore be proposed as a marker of SS.

Adult↗

Kinetics of local immune responses in mouse Peyer's patches after respiratory exposure to flour.

Peyer's patches play a major role in the initiation of mucosal immune responses since most environmental antigens gain access to the digestive tract and are therefore liable to achieve contact with their specialized dome epithelium. We investigated kinetics of immunophenotypic modifications induced in the cells from murine Peyer's patches in a model of intensive controlled exposure to flour dust. Three groups of mice were placed in an atmosphere enriched in wheat flour for 3, 6 or 10 consecutive days. Although Ig bearing B cell numbers did not vary, the numbers of IgA-containing plasma-cells increased significantly during the course of exposure. A significant and increasing imbalance of the CD4/CD8 ratio was noted, as early as after 3 days of exposure related both to increasing numbers of CD4+ and decreasing numbers of CD8+ cells. These data indicate a rapid kinetics of immune responses in Peyer's patches in an original model of controlled respiratory challenge.

Animals↗

Isoelectric restriction of human immunoglobulin isotypes.

The partition of human serum immunoglobulins along a pH gradient of ampholynes was investigated using the recently developed method of preparative isoelectrofocusing. Each isotype was demonstrated to display a specific pI range, with limited overlapping. IgA appear to be the most acidic serum immunoglobulins while IgG are clearly basic.

Adolescent↗

Altered partition of T cell subsets in the peripheral blood of healthy workers exposed to flour dust.

Occupational exposure to organic compounds can induce obvious immunological disorders or more subtle modifications. We investigated peripheral blood lymphocyte subsets in 34 bakers and 82 millers exposed to wheat flour dust, and 51 salt factory workers. Significantly decreased levels of CD4+, CD8+, CD57+ and CD8+/57+ cells were noted in mill workers, and of CD57+ cells in bakers. CD29+ and CD4+/CD29+ cells were significantly lower in millers, CD4+/CD45RA+ cells higher in all exposed workers. The lower numbers of positive cells noted in millers appeared associated to significantly higher (p < 0.001) levels of CD29 and CD45RA expression as measured by fluorescence intensity. These data are opposite to those previously reported in asthmatic workers exposed to flour dust. Since the individuals tested here were clinically healthy, the alterations of T-cell subsets observed could be interpreted as a successful attempt at immunoregulation maintaining homeostasis.

Antigens, CD↗

CD31, CD62E, and CD62P identify a specific pattern of endothelial activation in Graves' disease.

The different degrees of lymphocytic infiltration observed in Graves' disease, Hashimoto's disease, and De Quervain thyroiditis suggest that the regulation of adhesion molecules expressed on endothelial cells could be different in these autoimmune disorders of the thyroid. Using immunohistological techniques, we observed that thyroid samples from patients with Graves' disease displayed a characteristic pattern of capillary proliferation, with CD62P, CD62E, and CD31 expression on endothelial cells. This was different from the pattern and size of endothelial cells expressing adhesion molecules in the two other types of thyroiditis where larger vessels and high endothelial venules were stained. Almost no signs of endothelial cell activation could be seen in a comparative series of non-autoimmune disorders.

Adolescent↗

Ovarian autoimmunity and corticotherapy in an in-vitro fertilization attempt.

This case report describes a successful pregnancy and delivery in a woman presenting with ovarian autoimmunity who had previously been involved in two unsuccessful in-vitro fertilization (IVF) attempts. Ten days before a third attempt, she began a regimen of 25 mg per day of prednisolone which was continued throughout the whole IVF protocol. Ovulation was induced by human menopausal gonadotrophin. After administration of 5000 IU of human chorionic gonadotrophin, 18 oocytes were collected. At 48 h after insemination with the patient's husband's spermatozoa, four 4-cell pre-embryos were transferred. A singleton pregnancy developed and led to the birth of a girl who is doing well 10 months later.

Adult↗

Serum secretory IgA and IgM and free secretory component in IgA nephropathy.

IgA nephropathy (IgAN) is characterized by the presence of IgA and C3 deposits in the mesangium. Mesangial IgA is mostly dimeric IgA1 with a J chain, lacking a secretory component. In view of the recent demonstration of elevated serum levels of secretory component and secretory IgA in liver disease and HIV infection associated with hyper-IgA, we measured the serum secretory component in 50 IgAN patients and 45 controls. Free secretory component and secretory IgA and IgM levels were determined by enzyme-linked immunosorbent assay. Normal or low levels were found patients. These data support previous work suggesting that in IgAN circulating and probably mesangial IgA do not originate from the epithelial compartment of the mucosal immunoglobulins as it is the case in other hyper-IgA diseases.

Adolescent↗

Expression and long-term prognostic value of CD34 in childhood and adult acute lymphoblastic leukemia.

Clinical and laboratory characteristics at diagnosis, and long-term (up to 7 years) evolution, were analysed in 156 patients (66 adults and 90 children) with acute lymphoblastic leukemia (ALL), according to the expression of CD34. Eighty-three patients had CD34+ and 73 patients CD34- blasts at diagnosis. In adults, CD34+ ALL was more often of B-lineage (p = .003). White blood cell counts were higher both in children with CD34-B-lineage ALL (p = .02) and adults with CD34-T-lineage ALL (p - .05). Adult patients with CD34-T-lineage ALL were older (p = .04) and had more frequent splenic or liver enlargement (p = .02). Children with CD34+ ALL had a significantly (p = .04) longer event-free follow-up than CD34- children. Survival curves showed that after induction of remission, relapses were less frequent during the first 2 years for patients with CD34+ B-lineage ALL. After 2 years, however, event-free survival curves of CD34+ and CD34- patients merged. Thus it seems that CD34+ has no significant benefit for ALL patients.

Adolescent↗

Light chains of immunoglobulins in human secretions.

Immunoglobulin kappa light chains are predominant in normal human serum and a kappa/lambda ratio of 1.7 to 2 has been reported. However, little is known of the partition of light chains in secretions. The levels of IgA, kappa and lambda were assayed by nephelometry in a series of secretions and in normal human serum. Although kappa chains remained predominant, the different secretions studied could be classified according to their kappa/lambda ratio. In saliva (P < 0.001), nasal fluid (P = 0.01) and tears (P = 0.04) the kappa/lambda ratio was significantly lower than in serum. Conversely, higher kappa/lambda ratios were obtained in gastric juice (P = 0.005) and hepatic bile (P = 0.004) and no significant difference was noted between serum and gall bladder bile (P = 0.62). The lower ratios were all observed in fluids produced by glands surrounded by lymphoid tissue included in the mucosae-associated lymphoid tissue. These data strengthen previous observations that suggest a preferential production of lambda chains in human mucosae.

Adult↗