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J C Brouet

Publications and source records attributed to J C Brouet.

At least 145 records · Page 8Linked to original sources

Autoantibodies to nuclear lamin B in a patient with thrombopenia.

We report the characterization of novel nucleus specific autoantibodies in the serum of a patient with systemic lupus erythematosus. Immunofluorescent staining of cycling cells and absorption experiments localized the antigen to the nuclear envelope. Two-dimensional gel electrophoretic analysis of immunoprecipitated nuclear proteins show the antigen to be an acidic polypeptide (IP approximately 5.4) of 68 kDa molecular mass. It has been identified as lamin B, one of the three major nuclear envelope polypeptides of mammalian cells. Antibodies shown to be polyclonal immunoglobulin Gs, were directed against determinant(s) of the protein that have apparently been conserved during evolution. They do not appear to be related to other autoantibodies present in the serum (anti-DNA and anti-platelet). The nuclear specificity shown by these antibodies further demonstrates the antigenicity of proteins related to intermediate filament proteins in patients with autoimmune disorders.

Adult↗

Heterogeneity of responsiveness of chronic lymphocytic leukemic B cells to B cell growth factor or interleukin 2.

We compared the proliferative responses of purified human leukemic B cells from 12 cases of chronic lymphocytic leukemia to highly purified B cell growth factor (BCGF) and recombinant interleukin 2 (rIL 2) spontaneously, and in a coactivation assay using anti-mu monoclonal antibodies. Heterogeneity of response to one or the other lymphokine was observed from case to case. Spontaneous responses were observed to BCGF in one case, to rIL 2 in 3 cases and to both lymphokines in one other case. Costimulation with anti-mu monoclonal antibody induced a proliferative response to BCGF in 3 additional cases and to rIL 2 in 4 cases. Interestingly, cells from BCGF-responsive cases also proliferated in response to rIL 2. The leukemic B cells from 4 chronic lymphocytic leukemia patients were unresponsive. Cells from 5 cases expressed IL 2 receptors, although rIL 2 induced a direct proliferative response in only 3 of these cases. Expression of the B cell activation antigen B5 was associated to BCGF responsiveness.

Antigens, Neoplasm↗

Spontaneous recurrent fetal wastage and autoimmune abnormalities: a study of fourteen cases.

Case records of 14 women with spontaneous recurrent fetal wastage were analyzed. Venous and/or arterial thrombosis developed in nine patients and vasospastic symptoms in eight. Every patient had some kind of autoantibodies: prothrombin activation inhibitor was present in seven cases, anticardiolipin in five, and, antimitochondrial antibodies in two. Antinuclear antibodies were present in seven cases, and significant titer of antibodies to single-stranded DNA in nine cases. With a mean follow up of 6.5 years no patient developed systemic lupus erythematosus. It is suggested that such women have a peculiar form of vasculitis.

Abortion, Habitual↗

Cytogenetic studies in four cases of alpha chain disease.

Cytogenetic studies were performed in four cases of alpha chain disease. Chromosomal abnormalities were found in the lymphoid cells of the mesenteric lymph nodes of three patients, two of whom had not reached the stage of overt malignant lymphoma. In two instances, a rearrangement of 14q32, resulting from a t(9;14)(p11;q32) and a t(2;14)(p12;q32) was observed. One case showed complex rearrangements including t(5;9). No abnormalities were found in the intestinal tumor of the fourth case with immunoblastic lymphoma. It is concluded that alpha chain disease is a clonal proliferation with frequent alteration of chromosome #14 at band q32 resulting from translocations that differ from those observed in the vast majority of other non-Hodgkin lymphomas.

Chromosome Aberrations↗

Differentiation by interleukin 2 of a subpopulation of human B cells.

We demonstrate here that purified recombinant interleukin 2 (IL-2) induces a sizeable population of highly purified spleen B cells, by both negative and positive (cell-sorting) selection to differentiate polyclonally into plasma cells. This effect is seen at concentrations of IL-2 that are optimal for T-cell growth (1-5 U/ml) and is inhibitable by anti-Tac monoclonal antibody. In contrast, peripheral blood B cells show no or minimal terminal differentiation. When spleen B cells were separated into small and large cells, only the latter responded to IL-2; since this state of activation is achieved in vivo, these data support the possibility that IL-2 may be a physiological mediator in B-cell differentiation.

B-Lymphocytes↗

Characterization of a monoclonal antibody recognizing a monomorphic determinant of the alpha chain of class II DQ antigens.

We have characterized a monoclonal antibody (L2) specific for a determinant of Human DQ class II antigens. After immunoprecipitation and immunofluorescence analysis performed on a panel of DR homozygous cell lines and HLA deleted mutants, it behaves like a monomorphic anti-DQ reagent and does not react with the products of the various DR alleles. On immunoblotting, it reacts with an epitope of the DQ alpha chain.

Antibodies, Monoclonal↗

Interleukin 2-induced proliferation of leukemic human B cells.

The proliferative responses of purified leukemic human B cells from nine B cell chronic lymphocytic leukemias to recombinant interleukin 2 (IL-2), spontaneously, and after preactivation by Staphylococcus aureus Cowan I (SAC) or anti-mu antibodies were studied. Three patterns of response were observed: (a) no response (three cases); (b) a moderate spontaneous response enhanced by anti-mu (one case); (c) a high proliferative response after preactivation by anti-mu and/or SAC (five cases). IL-2 could also trigger normal B cells, purified from spleen, to proliferative after preactivation by anti-mu or SAC. These results provide evidence that IL-2 is a lymphokine that acts physiologically on both B and T cells.

Antibodies, Anti-Idiotypic↗

Distribution of class IIDQ antigens on normal and leukemic lymphoid cells.

The distribution of DQ as well as DR antigens was examined on lymphoid and monocytic cells at different stages of differentiation. In the B cell series, both immature and differentiating (under Staphylococcus aureus or pokeweed mitogen stimulation) B cells often lacked DQ molecules; among surface IgM+ and IgD+ cells, both DQ and DR molecules were detected except on cells from 30% of the lymphoid malignancies studied. T cells expressed DQ molecules only after stimulation; a DQ-DR+ phenotype was observed in a large number of cells after allogeneic stimulation, in certain antigen-specific T cell lines as well as in T cell lymphomas, suggesting that class II antigens had a distinct pattern of regulation. In the monocytic lineage, DQ molecules were expressed by most lymph node monocytes and only a low percentage (20%) of circulating monocytes.

Antigens, Neoplasm↗

The association of chronic lymphocytic leukaemia and multiple myeloma: a study of eleven patients.

We present haematological and immunological data obtained in 11 patients with the rare association of chronic lymphocytic leukaemia (CLL) and multiple myeloma (MM). CLL occurred before MM in six cases and both diseases were diagnosed simultaneously in five. With regard to CLL, no peculiar clinical feature was found; in six patients, MM was characterized by extra-osseous lesions. A significant remission (3-7 years) was obtained in three patients. In six patients, CLL and plasma cells synthesized Ig molecules with different light chains, probably indicating the coexistence of two distinct clonal proliferations. In two cases where monoclonal Ig synthesized by both types of cells had the same type of light chains, studies with anti-idiotypic antibodies showed that the two proliferations were also distinct. The pathophysiology of this rare association is discussed in the light of these findings and of data from the literature.

Aged↗

Associated chronic lymphocytic leukemia and multiple myeloma: origin from a single clone.

We investigated the clonal relationship of malignant cells in a patient affected with both chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). CLL cells and malignant plasma cells synthesized IgG1 kappa and IgA kappa molecules, respectively; these monoclonal Ig shared idiotypic determinants, providing evidence that a single clonal disease occurred in this patient. Furthermore, when leukemic CLL cells were driven to differentiate in vitro to immunoblasts and plasma cells, a switch from IgG to IgA occurred in a significant percentage of cells that were double producers. These data suggest that, in some circumstances, CLL leukemic B cells may reach a more mature state, leading to the occurrence of clinical MM.

B-Lymphocytes↗

Immunologic markers of Burkitt's lymphoma cells.

Lymphocyte markers were studied on fresh cells from 30 patients with Burkitt (L3) leukaemia and cell lines derived from endemic and non-endemic Burkitt's lymphoma (BL) patients. We observed day-to-day variations of lymphocyte marker expression by cultured lines and, occasionally, differences between fresh and cultured cells. In L3 leukaemia, a wide range of phenotypes, including pre-B cell and mature monoclonal IgM + IgD positive B-cell phenotypes, was observed. Most often, the cells expressed high-density monoclonal surface IgM without IgD and lacked IgG Fc, complement and Epstein-Barr virus receptors. Blast cells from rare patients featured monoclonal IgG or IgA instead of IgM. Cases with light chains of the lambda type were more frequent than those with kappa chains. Monoclonal immunoglobulins were found in serum or urine from eight of 20 patients studied. These results are compared with data from the literature on endemic and non-endemic BL and discussed with respect to the maturation stage reached by the cells. In the study of both fresh and cultured cells, we demonstrated a correlation between variant chromosomal translocations and light-chain types, the cells from patients with a t(2;8) translocation expressing kappa and those with a t(8;22) expressing lambda chains, with one exception Vimentin expression was absent or weak in most BLs studied (lines or fresh cells) and in cells from patients with Langer-Giedion syndrome, in contrast to most other lymphomas and leukaemias and normal lymphoblastoid cell lines.

Burkitt Lymphoma↗

Expression of vimentin intermediate filament cytoskeleton in acute nonlymphoblastic leukemias.

Since vimentin intermediate filament (IF) expression in hemopoietic cells varies with the cell lineage as well as the state of differentiation of the cells, we studied the vimentin cytoskeleton by direct immunofluorescence and electron microscopy in 50 cases of acute nonlymphocytic leukemias. We found that malignant cells tend to reproduce the vimentin organization characteristic of their normal cellular counterpart. Thus, in M2 and M3 leukemias (French-American-British classification), vimentin was often reduced to a juxtanuclear bundle of filaments contrasting with the rich filamentous network expressed by M4 or M5 leukemias. In erythroblastic leukemias (M6) and megakaryoblastic leukemias, both identified by the expression of lineage-specific antigens, the absence of vimentin IFs could be correlated with the level of differentiation reached by the blasts. M1 leukemias displayed an abnormal pattern of vimentin organization with aggregated filaments giving a ring-like structure. However, no abnormality of the vimentin polypeptide could be detected by two-dimensional electrophoresis. These results show that the expression of the vimentin IF cytoskeleton may be a useful marker of differentiation in the study of leukemic cells.

Acute Disease↗

Characterization of a human monoclonal IgM with antibody activity to dsDNA.

We report here the characterization and fine specificity of a human monoclonal IgM lambda reacting with double stranded DNA. The purified IgM and its Fab fragment bind to DNA in the Farr or Crithidia lucilae assays as well as in an immunoenzymatic test. In the latter case, binding was inhibited by native DNA, by DNA alternative co-polymers and by some homopolymers only, but not by monodeoxyribonucleotides and ribonucleotides. Since cardiolipin and phosphatidic acid were good inhibitors, these data suggest that the monoclonal IgM reacts with the sugar phosphate backbone of deoxyribonucleic acids. Interestingly, the patient was affected with both Waldenström's macroglobulinaemia and pernicious anaemia without any symptoms of systemic lupus erythematosus.

Aged↗

[Intestinal involvement and exudative enteropathy in Waldenström's macroglobulinemia].

The case of a 60 year old man in whom diarrhea, steatorrhea and protein losing enteropathy developed one year after the diagnosis of Waldenström's macroglobulinemia is reported. Histological study of multilevel peroral biopsies of the small bowel mucosa showed the following features: a) lymphangiectasia, b) intralymphatic and interstitial deposits composed of lipids and immunoglobulin M of the kappa type (as demonstrated by specific histoimmunofluorescence), c) a mild lymphoplasmocytoid infiltrate, corresponding to the location of Waldenström's macroglobulinemia. The patient died six months later, in spite of improvement of his digestive tract functional abnormalities by a low-fat diet. Sixteen cases of small intestinal involvement have been reported during the course of Waldenström's macroglobulinemia, of which only one showed features similar to those found in our case. Lymphangiectasia appear to be due to mesenteric lymph node involvement by the tumoral process, and/or to increased blood viscosity; in turn the lymphangiectasia seem to be responsible for steatorrhea and plasma protein losses, since in our case both lipids and the immunoglobulin M-kappa were shown to cross the villous epithelium by immunohistochemistry.

Humans↗

[Peripheral neuropathy in Waldenstrom's macroglobulinemia. Antibody activity of monoclonal immunoglobulin M directed against vimentin].

In two patients with Waldenström's macroglobulinaemia complicated with peripheral neuropathy, purified monoclonal immunoglobulin M showed antibody activity specifically directed against vimentin, a major polypeptide of mesenchymal cell cytoskeleton and therefore in Schwann's cell. The neuropathy was of the sensory-motor type. It was improved in one case by plasma exchanges combined with chemotherapy. The relevance of this original antibody activity to the pathogenesis of neuropathy is discussed.

Antibodies, Monoclonal↗

Antivimentin autoantibodies in angioimmunoblastic lymphadenopathy.

We evaluated the prevalence and specificity of smooth-muscle autoantibodies in 20 serum samples obtained from patients with angioimmunoblastic lymphadenopathy. Smooth-muscle antibodies in high titers were detected in 75 per cent of the samples. No such antibodies were found in 30 normal control serum samples or in 10 samples from patients with non-Hodgkin's lymphoma and 1 of 12 from patients with other types of polyclonal hypergammaglobulinemia were positive. The antibodies were polyclonal and belonged to the IgM, IgG, and IgA classes. They reacted with vimentin, the major polypeptide of the intermediate-filament cytoskeleton of mesenchymal cells. The pattern of tissue reactivity and absorption experiments both show that these antibodies recognize special antigenic determinants of the vimentin polypeptide that are shared by vimentin and other classes of intermediate-filament proteins - namely, keratin and desmin. The frequency of this unusual autoantibody activity in angioimmunoblastic lymphadenopathy suggests that, like hypergammaglobulinemia and a positive Coombs' test, it may represent a useful serologic marker for the disease.

Autoantibodies↗

[Lymphocyte subpopulations in hemophilic patients].

Monoclonal antibody analysis of peripheral blood T-cell subsets was performed in 23 multitransfused haemophiliacs, 5 children and 10 adults. Although none of the patients exhibited symptoms of acquired immune deficiency, 5 of them showed an abnormally low proportion of T-cells with reversal of the OKT4 (helper/inducer) to OKT8 (cytotoxic/suppressor) ratio. No evidence of cytomegalovirus infection was found. A search for antibodies to human leukaemia virus antigen P24 gave negative results. The relationship between this abnormality and transfusions is discussed.

Adolescent↗