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Biomedical subjects

M C Bene

Publications and source records attributed to M C Bene.

At least 19 recordsLinked to original sources

Coexpression of CD40 and class II antigen HLA-DR in Graves' disease thyroid epithelial cells.

In Graves' disease, thyroid epithelial cells abnormally express HLA-DR Class II molecules in the vicinity of lymphocyte infiltrates, suggesting that lymphocyte proliferation is sustained by the appropriate presentation of antigenic material. The ability of thyroid epithelial cells to provide the necessary second signals has however not been documented. The expression of HLA-DR, CD40, CD40L, CD80, and CD28 was investigated on thyroid samples from 30 patients (Graves' disease, n = 16; benign toxic adenoma, n = 8; multinodular goiter, n = 6). Apoptotic cells were searched for using the TUNEL method. CD40 appeared to be coexpressed with HLA-DR in Graves' disease patients samples and in two control samples also containing lymphoid infiltrates. Almost no apoptotic cells were found. These data suggest that thyroid epithelial cells from Graves' disease patients have the ability to successfully present autoantigens. The near absence of apoptotic cells in surrounding lymphoid infiltrates is in keeping with this efficient provision of a rescue second signal.

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

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

Serum anti-dextran antibodies in IgA nephropathy.

Abnormally high humoral responses have been described in IgA nephropathy (IgAN), towards antigens commonly involved in infectious events or food intolerance. Here we report a comparative analysis of humoral responses to a common environmental antigen, dextran B 512, present both in nonpathogenic microorganisms and normal diet. Dextran-specific IgG, IgA and IgM were assayed using an ELISA method in serum samples from 121 patients with IgAN, 40 controls and 32 patients with biopsy-proven renal diseases different from IgAN. Among the latter, 17 were transplant recipients. Anti-dextran IgG antibodies were found significantly (p < 0.05) more frequently and at higher levels in IgAN patients than in patients with other renal diseases. Anti-dextran IgA were at significantly (p < 0.05) higher levels in IgAN patients than in controls or untransplanted NIgAN patients. However, similarly elevated levels of anti-dextran IgA were found in IgAN patients and transplanted patients with other renal diseases. These data confirm that IgA and IgG responses towards common antigens are elevated in IgAN, possibly as a consequence of the pathogenesis of this disease rather than because of renal impairment. Moreover, since the same degree of dysregulation was noted in the control group of transplanted patients whose initial diagnosis was not IgAN, these data favour the hypothesis of a global dysregulation of the IgA system in IgAN, yielding enhanced humoral immune responses to possible pathogens and diet antigens.

Adult

Proposals for the immunological classification of acute leukemias. European Group for the Immunological Characterization of Leukemias (EGIL).

Criteria for the immunological classification of acute leukemias are proposed by a recently established European group designated EGIL. The main aims of EGIL are to establish guidelines for the characterization of acute leukemias based on marker expression and provide a uniform basis for the diagnosis of the various types of these hemopoietic malignancies which should be helpful for future multinational clinical and laboratory investigations. Within the two major types (B and T cell lineage) of acute lymphoblastic leukemia (ALL), several groups are delineated according to the degree of cell differentiation. Within the acute myeloid leukemias (AML), only three subtypes as defined by the FAB classification: M0-AML, M6-AML and M7-AML, can be unequivocally defined by immunological markers; prospective studies are undertaken to see whether characteristic immunological profiles are associated with particular AML subtypes defined by specific cytogenetic abnormalities. Criteria for the definition of biphenotypic acute leukemia (BAL) are devised and a scoring system is outlined aimed to distinguish BAL from those acute leukemias with expression of a marker from another lineage. In addition, an uncommon subset of acute leukemias with no evidence of lymphoid or myeloid differentiation is recognized and the useful panel of markers to investigate and establish the cell nature of the acute leukemias is outlined. EGIL will focus in the future on testing the reproducibility of the proposed guidelines, particularly those for BAL, assessing their clinical value within a framework of multicentric trials and setting up uniform methodological criteria.

Acute Disease

Immunohistological analysis of macrophages, B-cells, and T-cells in the mouse lung.

BACKGROUND: Numerous studies have described the anatomy of the large lymphoid aggregates of bronchus-associated lymphoid tissue (BALT) in rabbits and rats. Less work has been performed on other immunocompetent areas of the respiratory tract, and available data again mostly describe rabbit or rat tissues. Little is known therefore of the microanatomy of the mouse lung immune system. METHODS: We report a study, devised in order to establish the immunohistological characteristics of normal healthy mice lungs, performed on whole lungs from 22 mice of various strains and/or ages. Snap frozen tissues were serially sectioned and analysed using histochemistry and immunohistological techniques. Scattered macrophages, IgA plasma cells, B and T cells were enumerated in each sample. RESULTS: The largest population was that of macrophages. B-cells were numerous in all mice but 3 adults. T-cells were always present, L3T4+ often more numerous than Lyt2+ cells. Small lymphoid aggregates, composed of B or T cells (L3T4+ and Lyt2+) were seen in all mice, in the vicinity of a bronchiole and a vein. In 12/22 mice, a peculiarly elongated para-esophageal lymph node with large peripheral B-cell nodules and medullary T-cells was observed. In the five strains of mice studied, large variations were noted, affecting all the cell types studied, and related either to age or strain. CONCLUSION: Besides providing a qualitative description and quantitative analysis of immunocompetent cells, this work reports age and strain-related variations in these cells' distribution. These data could be relevant for studies involving the analysis of mice respiratory immune responses to environmental antigens.

Aging

Comparative immunohistochemical characteristics of human choroid plexus in vascular and Alzheimer's dementia.

Autoimmune alterations are indirectly supported in Alzheimer's disease by the demonstration of circulating antibodies directed to the epithelial basement membrane (BM) of the choroid plexus. We used immunohistochemical methods to compare the characteristics of choroid plexuses obtained postmortem from 15 patients. Six had a diagnosis of Alzheimer's disease, five had multi-infarct dementia (MID), and one suffered from mixed dementia. Similar tissue from three age-matched, non-demented controls was studied as well. Age-related psammoma bodies, lipofucsin, and flattened epithelial cells were present in all cases. Specific alterations were evident in Alzheimer's disease patients only. These were comprised of pseudolinear deposits of immunoglobulin (Ig)G and coarse deposits of C1q along the thickened and segmented epithelial BM, and were associated with IgM in five cases. Although no lymphoid infiltration was demonstrated, MHC Class II+ macrophages were observed in the plexus stroma, and numerous epithelial cells were class II+. These observations suggest that immune alterations, possibly of autoimmune origin, may be involved in Alzheimer's disease, leading to severe lesions of the choroid plexus. Such anomalies could be responsible for some of the alterations of cerebrospinal fluid (CSF) production or composition noted in this disease.

Aged

Antibody-producing cells in peripheral blood and tonsils after oral treatment of children with bacterial ribosomes.

The efficacy of ribosomal preparations as mucosal immunostimulants was examined in the peripheral blood and tonsils of 14 children, before and after 28 days of oral treatment with D-53, a preparation of ribosomes from Klebsiella pneumoniae, Streptococcus pneumoniae, Haemophilus influenzae and Streptococcus pyogenes. Tonsils from 10 untreated children were used as controls. Immunofluorescence and ELISAspot were performed to analyse variations in the numbers of immunoglobulin-containing and immunoglobulin-secreting B-cells. Both isotypic and antigenic specificities of these two types of cells were investigated. Significant differences were observed after treatment in the peripheral blood as well as between tonsils from treated and untreated children. In the peripheral blood a significant increase in immunoglobulin-secreting cells directed against antigenic specificities of D-53 was the major change. In tonsils, higher numbers of specific immunoglobulin-containing and secreting cells, and higher numbers of IgA-secreting cells were induced in treated children. These data support the efficacy of D-53 as an oral immunostimulant.

Administration, Oral

Microparticle-enhanced nephelometric immunoassay of anti-thyroid peroxidase autoantibodies in thyroid disorders.

Crude thyroid peroxidase extracted from human thyroid microsomes was covalently bound onto polyacrylic and polyfunctional copolymerized microparticles. We observed agglutination of the thyroid peroxidase-microparticle conjugate with 13 monoclonal antibodies (mAbs) specific for epitopes on four different antigenic domains of human thyroid peroxidase (TPO; EC 1.11.1.7), after addition of anti-mouse immunoglobulins. We quantified agglutination by measuring with a specially designed nephelometer the light scattered by the conjugates. This allowed us to develop a microparticle-enhanced nephelometric immunoassay for human anti-TPO autoantibodies (aAbs) with defined epitopic specificity, based on the ability of aAbs to inhibit mAb-induced agglutination. Applied to patients with autoimmune thyroid diseases, this assay confirmed the polyclonality of anti-TPO aAbs and their preferential reactivity toward epitopes located on the A and B antigenic domains of the TPO molecule. The same specificities seem to be present in patients with Hashimoto thyroiditis or Graves disease.

Autoantibodies

CD2 + CD19 + acute lymphoblastic leukaemia in 16 children and adults: clinical and biological features. Groupe d'Etude Immunologique des Leucémies (G.E.I.L.).

A small population of CD2 + CD19 + lymphoid cells have been suggested to be common lymphoid progenitors. CD2 + CD19 + biphenotypic ALL account for less than 2% of ALL. We analysed the clinical and laboratory features of a series of 16 patients with CD2 + CD19 + ALL. The incidence of tumoural syndrome was comparable to a previously published series of pre B-ALL but significantly different from that of T-ALL. The mean age of the 11 children of this series was 101 +/- 46 months, and differed significantly from that of children with pre B-ALL (P < 0.01). Complete remission was obtained for all patients except two adults. Only three relapses have been observed. Regardless of the presence of CD2 +, the 16 ALL could be classified as pre B-ALL, according to the nomenclature used by the GEIL. Nine samples could be analysed by Southern blotting. Seven had rearranged IGH genes, usually on both chromosomes. IGK rearrangement was observed in three cases. Only one case had rearranged both TCRG and TCR beta. The patterns observed here and those reported previously follow that of the pre B-ALL which confirms the engagement of most CD2 + CD19 + biphenotypic ALL in the B-lineage.

Adult

Prophylactic use of ganciclovir for allogeneic bone marrow transplant recipients.

Ganciclovir which has proved effective in the treatment of cytomegalovirus (CMV) infection was given prophylactically to 40 bone marrow transplant (BMT) patients pre and post-transplant in seropositive patients and post-transplant in seronegative patients with a seropositive donor. All patients were transfused with screened blood products and 33 received CMV hyperimmune globulin. They were compared with an historical control group consisting of 39 patients who had received significantly more unscreened blood products (p = 0.01) and less HLA-mismatched marrow transplants (p = 0.05). Toxicity of ganciclovir was hematological-neutropenia was responsible for cessation of the drug in seven patients and transfusion requirements were significantly higher in the ganciclovir group. Non-hematological toxicity did not occur in any patient. Only one patient (2.5%) experienced symptomatic CMV infection and no patient developed CMV pneumonitis. In contrast, in the control group, 23 (59%) patients had clinical symptoms of CMV infection (p < 0.0001) and 4 (10%) experienced CMV pneumonitis (p < 0.01). Ganciclovir significantly reduced the incidence of positive CMV antigenemia (7.5% in the treated group vs 72% in the control group; p < 0.01). However, ganciclovir delivery did not result in an improved overall survival due to a higher rate of regimen-related deaths and chronic GVHD mostly in patients transplanted from an HLA-mismatched donor. The prophylactic administration of ganciclovir abrogates CMV pneumonitis and considerably reduces the incidence of CMV infection in BM recipients at high risk of developing this disease after transplantation.

Adolescent

Peripheral B cells with intracytoplasmic mu chains in HIV infection.

Besides the major alteration of T lymphocytes, B-cell anomalies have been reported in HIV infection, related to late stages of B-cell maturation, and considered to result from the dysregulation of T/B interactions. Because T cells are also involved in the control of lymphopoiesis and/or because of specific alterations of the B lineage, anomalies of B-cell maturation could occur in HIV-infected patients. We investigated the presence of immature pre-B lymphocytes, characterized by cytoplasmic mu chains, in 35 peripheral blood samples from healthy controls, 82 from HIV-positive/non-AIDS patients, and 45 from AIDS patients. Significant numbers of such cells were observed in 48% of HIV-seropositive patients and in 40% of the patients with AIDS disease. The presence of pre-B cells correlated with higher numbers of CD8+ and/or CD57+ cells and of peripheral lymphocytes. These data suggest that B-cell dysregulation in HIV infection may lead to the abnormal release of immature B cells in the peripheral blood. This observation may be interpreted as a sign of bone marrow activity.

Acquired Immunodeficiency Syndrome