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Biomedical subjects

C Griscelli

Publications and source records attributed to C Griscelli.

At least 127 records · Page 7Linked to original sources
PubMed1988

Xp21 DNA microdeletion in a patient with chronic granulomatous disease, retinitis pigmentosa, and McLeod phenotype.

The clinical, biochemical, and molecular analysis of a patient with chronic granulomatous disease (CGD), retinitis pigmentosa (RP), and McLeod phenotype and of his parents demonstrated the X-linked transmission of these three traits in this family and a deletion of the entire X-CGD gene of the patient DNA. All but one other DNA markers tested, including those in Xp21, were present. These findings strongly suggest that the McLeod locus and at least one XL RP gene are closely linked to the X-CGD locus in the Xp21 region of the human X chromosome.

Child, Preschool↗
PubMed1988

The effect of RU 41740 on the in vitro maturation of human B-cells.

We have tested the effect of a Klebsiella pneumoniae extract, RU 41740, and its lipopolysaccharidic fraction (LPS-LAP) on the in vitro activation of human B-cells. Two models have been used: the polyclonal activation induced by pokeweed mitogen and the specific antibody production to mannan, a polysaccharide extracted from the cell wall of Candida albicans. We have shown that RU 41740, and especially its lipopolysaccharidic fraction, significantly increases the production of immunoglobulins and specific antibodies. This effect is mediated by T-lymphocytes, since preincubation of isolated T-cells, but not of non-T-cells, resulted in the same effect. Together with the known enhancing effect of LPS-LAP on T-cell proliferation, these data strongly suggest that LPS-LAP increases the production of B-cell-activating lymphokines by T-cells.

Adjuvants, Immunologic↗
PubMed1988

Analysis of the membrane glycoproteins of platelets in the Wiskott-Aldrich syndrome.

We have examined the plasma membrane glycoproteins of platelets from three unrelated patients with the Wiskott-Aldrich syndrome. Single- or two-dimensional SDS-polyacrylamide gel electrophoresis was performed. Glycoproteins were located by staining for carbohydrate, or by autoradiography when the platelets had been surface-labelled with 125I prior to solubilization. In one patient a slight decrease in the 125I-labelling intensity of GP Ib, GP Ia and a 125I-labelled polypeptide of Mr 168,000 were noted. For the two other patients the glycoprotein profiles were indistinguishable from those of normal subjects. These results clearly indicate that abnormalities in platelet membrane glycoproteins are not a common trait among Wiskott-Aldrich patients, and thus cannot be regarded as primary defects in this disease.

Adolescent↗
PubMed1988

Treatment of severe Epstein-Barr virus-induced polyclonal B-lymphocyte proliferation by anti-B-cell monoclonal antibodies. Two cases after HLA-mismatched bone marrow transplantation.

We treated two children who developed Epstein-Barr virus-induced polyclonal B-cell proliferation after HLA-mismatched bone marrow transplantation for congenital immunodeficiency with two monoclonal anti-B-cell antibodies. Lymphoproliferative syndrome occurred between 50 and 60 days after bone marrow infusion, and was diagnosed by the presence of spontaneously growing B cells containing Epstein-Barr-nuclear antigen in the blood and bone marrow. The mouse monoclonal anti-B-cell antibodies used were a CD21-specific antibody recognizing the CR2 receptor on B cells (BL13, IgG1) and a CD24-specific antibody binding B cells at all steps of differentiation (ALB9 IgG1). Both antibodies were given intravenously (0.2 mg/kg/body weight.d for 10 days). All clinical and biological manifestations resolved within 3 weeks of treatment. Recurrence was not seen at 18- and 15-month follow-ups. T-cell function developed normally; B-cell function remained partially deficient in one patient 21 months after bone marrow transplantation. These results suggest that monoclonal anti-B-cell antibodies could be useful in controlling severe polyclonal lymphoproliferative syndrome in profoundly immunodeficient patients after bone marrow transplantation.

Antibodies, Monoclonal↗
PubMed1988

The antibody spectrum in individuals with defect expression of HLA class II and the LFA-1 glycoprotein family genes.

HLA class II antigens and the LFA-1 (lymphocyte function-associated type 1) glycoprotein family are cell surface structures of central importance in many lymphocyte reactions. Specific antibodies are normally restricted to particular IgG subclasses. In order to study the mechanism of isotype restriction we have analysed specific IgG1, IgG2, IgG3 and IgG4 antibodies directed against a number of different protein and polysaccharide antigens in individuals with HLA class II or LFA-1 deficiency. HLA class II deficiency resulted in decreased total IgG2, IgG4 and IgA in 4/4 patients, whereas total IgM and IgG were low in 2/4. In HLA class II deficiency the levels of specific antibodies directed against protein as well as polysaccharide antigens were frequently low. Virtually normal total as well as specific antibody levels were found in individuals with both severe and moderate forms of LFA-1 deficiency. There was no clear evidence for an abnormal subclass pattern of specific antibodies with a shift from one subclass to an isotype which is normally not used, in any of the patient groups investigated.

Adult↗
PubMed1988

[Immunodeficiencies and lymphoma].

Primary immunodeficiencies (ID) lead to a high incidence of cancer, particularly of lymphomas. The risk excess varies according to the type of ID. Cellular IDs carry a very high risk, tumoral IDs have an intermediate risk while deficiencies of non-specific immunity bear no risk. Acquired IDs are also associated with an increased risk of lymphomas. The physiopathogeny of ID-associated lymphomas remains unknown, although several hypotheses have been proposed, including a defective immunological surveillance, repeated viral and antigenic stimulations and DNA repair anomalies.

DNA Repair↗
PubMed1987

Specific interleukin-1 inhibitor in serum and urine of children with systemic juvenile chronic arthritis.

Interleukin-1 (IL-1) activity and inhibition were studied in serum and urine from nine patients with systemic juvenile chronic arthritis (S-JCA). In afebrile patients IL-1 activity was normal or high. Serum from two afebrile S-JCA patients taken during a period of severe disease activity had an enhancing effect on the activity of exogenous IL-1. Secondary amyloidosis subsequently developed in one of these patients. In contrast, in febrile patients' serum and urine IL-1 activity was low, apparently reflecting the presence of a strong inhibitor of IL-1 activity measured by the inhibition of prostaglandin E2 production by synovial cells. This inhibition was greatest at the time of peak temperature, suggesting the possibility of feedback regulation during fever. This novel identification in S-JCA of a specific IL-1 inhibitor that competes at the IL-1 receptor level may be an important step in the understanding of the pattern of fever and the evaluation of disease in patients with S-JCA.

Adolescent↗
PubMed1987

Idiotypy of human anti-Candida albicans antibodies: recurrence, presence of a cross-reactive autoanti-idiotypic-like activity, and role in the induction of specific in vitro antibody response.

Rabbit anti-idiotypic antibodies (L12) were raised against human anti-mannan of Candida albicans (CA) antibodies isolated from the serum of a normal donor. The absorbed anti-idiotypic antiserum bound to donor anti-CA mannan antibodies but not to control immunoglobulins. Binding was inhibited by CA mannan but not by other polysaccharide antigens. L12 was shown to cross-react with anti-CA mannan-isolated antibodies or with anti-CA antibody-containing sera from individuals unrelated to the donor. IgG fraction isolated from the donor serum was repeatedly absorbed on CA mannan Sepharose to remove anti-mannan antibodies. This IgG fraction (named autoanti-idiotypic fraction) blocked, in a dose-dependent fashion, the binding of rabbit anti-idiotype to donor anti-CA mannan antibodies. Moreover, this CP-depleted IgG fraction cross-reacted with public idiotypic determinants of unrelated anti-CA mannan antibodies. Finally, L12 induced sensitized lymphocytes to produce anti-CA mannan antibodies in vitro in the absence of antigen.

Antibodies, Anti-Idiotypic↗
PubMed1987

Graft vs graft reaction resulting in the elimination of maternal cells in a SCID patient with maternofetal GVHd after an HLA identical bone marrow transplantation.

In a young girl with a severe combined immunodeficiency, the presence of circulating maternal T lymphocytes was proven by HLA typing. Manifestations of skin graft vs host disease were associated with the persistence of maternal cells. The patient received an HLA identical bone marrow transplantation from her brother without any conditioning. The bone marrow transplantation was quickly followed by a transient and dramatic increase in skin lesions associated with fever and the finding of a high number of circulating lymphocytes and eosinophils. Lymphocytes were shown to be of donor origin and exerted a spontaneous cytotoxic activity toward maternal cells. This activity progressively disappeared within 90 days, whereas maternal cells were no longer detected in patient's blood, and skin graft vs host disease was resolved within 8 wk. Cytotoxic activity was proven to be mediated by donor T lymphocytes specific for the mother's HLA antigens. The cytotoxic activity was demonstrated to be specific for the HLA class I molecules of the mother not shared with her daughter (HLA A1, B17) as shown by the use of a series of HLA typed cells as targets. In addition, cold K562 target cells did not block the cytotoxic activity, and the kinetics of the cytotoxic activity did not correlate with that of natural killer activity emergence after the bone marrow transplantation. Patient's serum did not contain antibodies toward maternal specific HLA class I antigen. Cytotoxic activity was totally blocked by anti-T3 monoclonal antibodies and partially by anti-T8 and anti-T4. It is thus likely that donor origin cytotoxic T lymphocytes were promptly activated after bone marrow transplantation and provoked the elimination of the maternal graft after a transient exacerbation of graft vs host disease manifestations. This observation represents one of the first examples of the possible role in vivo of allogeneic cytotoxic lymphocytes in humans.

Bone Marrow Transplantation↗
PubMed1987

LFA-1 beta-chain synthesis and degradation in patients with leukocyte-adhesive proteins deficiency.

The defective membrane expression of the adhesive protein family (LFA-1, Mo1 and p150,93) on leukocytes from certain patients with recurrent bacterial infections was shown to be secondary to the absence of synthesis of mature beta chain that is common to all three antigens (Springer et al., 1984, Lisowska-Grospierre et al., 1986). In all patients, studies of beta-chain biosynthesis that lead to this conclusion were performed using the monoclonal anti-beta chain antibody to isolate the beta subunit. Since this antibody detects the mature form of beta chain only, the potential presence of a precursor or of an abnormal beta chain in the patient's cells could not be tested. The availability of the polyclonal antibody to the purified beta subunit allowed us to re-examine the biosynthesis of the LFA-1 subunits in 3 affected children. In all 3 patients, the absence of membrane expression of the LFA-1, CR3 and p150,95 proteins was confirmed. The LFA-1 alpha-chain precursor of 170 kDa was detected in the lysates of PHA blasts of two children, but was not detected in the third. The beta-chain precursor of 85 kDa was isolated by the polyclonal anti-beta chain antiserum from the cytoplasm of phytohemagglutinin and Epstein-Barr virus-induced blasts of one patient. The same antibody precipitated some peptides of smaller mol. wt. from the cell lysates of 2 other patients. These results suggest that in this disorder the membrane nonexpression of the adhesive proteins is probably due to the structural abnormality of beta chain which, although synthesized, is rapidly degradated.

Antibodies, Monoclonal↗
PubMed1987

A monoclonal antibody (HML-1) defining a novel membrane molecule present on human intestinal lymphocytes.

A monoclonal antibody, HML-1, was produced by fusion of NSI myeloma cells with spleen cells of a mouse immunized with isolated human intestinal intraepithelial lymphocytes (IEL). Immunofluorescence studies of isolated cells, as well as immunoperoxidase staining of tissue sections, indicated that HML-1 labeled all the various subsets of human intestinal IEL, approximately 40% of lamina propria T cells, 30% mesenteric lymphoblasts and some lymphocytes in other mucosae, particularly IEL. Conversely, it revealed only rare cells in all other lymphoid compartments. Analysis by polyacrylamide gel gradient electrophoresis showed that HML-1 precipitated two major noncovalently bound components of approximate mol. masses of 105 and 150 kDa from human IEL. HML-1 thus defines a novel human membrane antigen present on a subpopulation of lymphocytes preferentially associated with epithelia, and particularly with the intestinal epithelium. The characteristics of this human antigen are very similar to those of an antigen we had previously described in the rat. The possible functional role of this novel class of lymphocyte membrane antigens as well as the nature of the mechanism that triggers their expression remain to be elucidated.

Adult↗
PubMed1987

Prenatal diagnosis of severe combined immunodeficiency with defective synthesis of HLA molecules.

The immunodeficiency associated with a defective expression of HLA molecules is an autosomal recessive disorder leading to death during childhood. We have performed prenatal diagnosis for six fetuses at risk for this disease by membrane immunofluorescence on blood lymphocytes and monocytes, using specific monoclonal antibodies for HLA class I and II molecules. Two pregnancies have been found to be affected. The diagnosis has been confirmed on each abortus by the study of the membrane expression of HLA class I and II molecules on blood lymphocytes and monocytes, and on thymic and splenic cells. The four other cases were found to be normal both during pregnancy and after birth. The detection of the defect as early as the 20th week of gestation allows selective termination.

Female↗
PubMed1987

Close linkage of random DNA fragments from Xq 21.3-22 to X-linked agammaglobulinaemia (XLA).

Linkage analysis of 15 families affected by X-linked agammaglobulinaemia (XLA) showed close linkage with three probes located towards the centre of the long arm of the X chromosome. No cross-overs were found using pXG12 (DXS94) lod 6.6 or S21 (DXS17) lod 4.4. One cross-over was found with 19.2 (DXS3). This confirms and extends a previous linkage study (Kwan et al. 1986) which demonstrated linkage with S21 and 19.2. Of the families 14 were informative for either pXG12 or S21 and these probes should thus be of great diagnostic value. No evidence of heterogeneity was found in the XLA families but several cross-overs within this region were detected in a family with the X-linked hyper-IgM syndrome confirming this disease as a separate clinical entity.

Agammaglobulinemia↗
PubMed1987

Mannan-specific and mannan-induced T-cell suppressive activity in patients with chronic mucocutaneous candidiasis.

We have studied T- and B-cell responses to antigens of Candida albicans in 18 patients suffering from chronic mucocutaneous candidiasis. We have shown that in vitro production of antibody to one of these antigens, mannan, was absent during the active phase of the disease and that this absence was consequent to the activation of specific CD8(+) and CD8(-) suppressor T lymphocytes. Such activation was also observed when control T lymphocytes were incubated in the presence of monocytes and a high concentration of mannan. This suppressive effect was specific to antigens of Candida albicans, was radiosensitive, and was not consequent to the secretion of prostaglandin E2. It appeared as well that the induction of these suppressor T cells was HLA-DQ restricted. The suppressor T-cell activity induced by antigens of Candida albicans in vitro is thus comparable to the suppressor T-cell activity observed in vivo in patients affected with chronic mucocutaneous candidiasis. Defective handling of mannan by monocytes could result in the accumulation of mannan, resulting in the activation of specific T suppressor cells and in the consequent cellular immunodeficiency specific to Candida albicans. Successful treatment of the candidiasis resulted in complete correction of the immune abnormalities.

Adolescent↗