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Biomedical subjects

A Morell

Publications and source records attributed to A Morell.

At least 55 records · Page 3Linked to original sources
PubMed1990

Immunomodulation by intravenous immunoglobulin.

In 1980, it was observed in a child with idiopathic thrombocytopenic purpura (ITP) that intravenous administration of pooled human immunoglobulin-G (IVIG) was followed by a rapid increase of the platelet count. Prompted by this finding, a pilot study and two prospective multicenter studies on children with ITP were organized. Efficacy of this new treatment for ITP was soon confirmed worldwide. In addition to the immediate effect, long-term observations following administration of IVIG suggested the occurrence of modulation of the immune response. Also, concomitant with studies on the mechanism of action of IVIG, the use of IVIG in the treatment of patients with other immune-related disorders was explored.

Adjuvants, Immunologic↗
PubMed1990

Serum immunoglobulin levels and natural antibodies to Haemophilus influenzae in hemodialysis patients: evidence for IgG subclass imbalances.

Humoral immune parameters were studied in 13 patients with end-stage renal failure on maintenance hemodialysis. Serum IgA, IgM and IgG concentrations were comparable to control values from 14 healthy blood donors. IgG subclass analysis revealed significantly increased IgG1 levels in the patients when compared to controls (p less than 0.01). In 3 patients, IgG2 deficiency was found, in one case associated with low IgG3 level. Concentrations and subclass composition of naturally occurring antibodies to Haemophilus influenzae type b (Hib) polysaccharide (PS) were measured using an indirect ELISA. In patients IgM and IgG, including IgG1 and IgG2 antibodies to Hib, presented no difference from controls. Subclass analysis of Hib specific IgG antibodies revealed that IgG2 accounted for a substantial amount of the anti-Hib PS antibody response in controls as well as in patients. We conclude that patients on maintenance hemodialysis present imbalances of immunoglobulin levels. However, the antibody response to certain PS antigens could remain unaffected by renal failure.

Aged↗
PubMed1989

Ig allotype-linked regulation of class and subclass composition of natural antibodies to group A streptococcal carbohydrate.

To determine the importance of genes located in or near the Ig constant regions in regulating the human antibody response, we correlated Ig allotypic markers with total Ig concentrations and natural antibody concentrations to the streptococcal group A carbohydrate (A-CHO) in 193 healthy adult blood donors. The major correlations between Ig allotypes and total Ig and specific antibody concentrations were observed with the Gm(f;n;b) haplotype. When compared with Gm(f;n;b) negative individuals, Gm(f;n;b) positives had significantly higher concentrations of total IgG2 (p less than 0.001) and IgG2 anti A-CHO (p less than 0.05), lower concentrations of total IgG1 (p less than 0.001) and IgG1 anti A-CHO (p less than 0.001), and lower concentrations of total IgM (p less than 0.001) and IgM anti A-CHO (p less than 0.05). We conclude that individuals with the Gm(f;n;b) haplotype respond preferentially with IgG2 rather than IgG1 subclass antibodies. This increased capacity to respond with IgG2 antibodies may be reflected in the magnitude of the total antibody response when the IgG2 subclass comprises a major proportion of the response, as occurs in the adult response to many polysaccharide Ag.

Adult↗
PubMed1989

A marker and putative pathoantigen of Hodgkin's cells.

A galactose-specific lectin, recently described by our laboratory, is immunologically demonstrable on the surface of neoplastic cells derived from patients with Hodgkin's disease. This Hodgkin's lectin is shown to be functionally and antigenically related to the galactose-N-acetylgalactosamine-specific lectin of the hepatocyte (HBP). Poly- and monoclonal antibodies against either the cytoplasmic tail or the cell-surface binding site of HBP recognize the Hodgkin's lectin as a 55 Kd protein. Expression of the 55 Kd antigen appears to be restricted to Hodgkin's disease involved tissues and cells of the monocyte/macrophage lineage. The putative identification of the Hodgkin's lectin as an ectosialyltransferase unique to Hodgkin's cells is supported by inhibition of enzymatic activity by anti-HBP antibodies. Cultured Hodgkin's cells, in analogy to purified HBP, agglutinate T-lymphocytes mediated by the Hodgkin's lectin. This cell-to-cell interaction results in the incorporation of sialic acid into lymphocyte surface asialoglycans as well as in the stimulation of lymphocyte proliferation. The function of the Hodgkin's lectin as lymphocyte agglutinant in vitro suggests its role as an immunomodulator contributing to the immunodeficiencies associated with Hodgkin's disease.

Antigens, Neoplasm↗
PubMed1989

Interferon gamma-treated human macrophages display enhanced cytolysis and generation of reactive oxygen metabolites but reduced ingestion upon Fc receptor triggering.

Human monocyte-derived macrophages treated with recombinant IFN-gamma (rIFN-gamma) and control cells were assessed for three distinct effector functions, all mediated by Fc receptors. rIFN-gamma-primed macrophage displayed markedly reduced phagocytosis of IgG antibody-coated erythrocytes. In contrast, antibody-dependent cytotoxicity towards IgG-antibody-coated erythrocytes and IgG-antibody-coated erythrocyte-induced generation of reactive oxygen metabolite production were increased. The decreased phagocytosis was observed microscopically, as well as in a spectrometric and a radiometric phagocytosis assay. Evidence is presented that the observed impairment in phagocytosis is not the result of increased extracellular lysis or intracellular catabolism of IgG-antibody-coated erythrocytes and that it is not observed with particles ingested in an Fc receptor-independent manner. Enhanced production of reactive oxygen metabolites was detected most clearly by measurement of luminol-dependent chemiluminescence. Antibody-dependent cellular cytotoxicity was shown to proceed also under conditions impeding phagocytosis, and rIFN-gamma-treated macrophage exerted enhanced antibody-dependent cellular cytotoxicity under these conditions too. In all three assays, functional alterations were optimally expressed after a treatment with 500 U/ml for 46 hr. Analysis at the single-cell level revealed that the IFN-gamma-induced alterations were expressed by all macrophages and not the property of distinct macrophage subpopulations. This and earlier studies suggest that the modulation of Fc receptor-mediated macrophage effector functions by IFN-gamma is in part a post-receptor-binding event.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1989

Quantitative assessment of human neutrophil chemiluminescence induced by opsonized Escherichia coli K-12.

The interaction of opsonized E. coli K-12 bacteria and polymorphonuclear leukocytes (PMN) was quantified, using luminol-enhanced chemiluminescence (CL) as a parameter of PMN stimulation. On a double-logarithmic scale light emission depended on the opsonin concentration used during pre-opsonisation. The most potent CL-inducing agent was fresh human serum, and its stimulatory activity depended on an intact complement (C) system. Both inactivation of C by heating or blocking the classical C pathway with EGTD decreased the CL-inducing potency by a factor of 8 to 16. Hypogammaglobulinemic heated serum mediated little CL. IgG for intravenous use mediated CL generation, but reduction/alkylation and sulphitolysis reduced the stimulatory power. Evidence is presented that the anti-K-12 antibodies within commercial IgG and IgM used for substitution do not improve the stimulatory power of IgG-deficient, IgM- and C-sufficient serum, unless very high Ig concentrations are substituted.

Agammaglobulinemia↗
PubMed1989

Idiopathic thrombocytopenic purpura (ITP): immunomodulation by intravenous immunoglobulin (IVIg).

ITP is a destructive thrombocytopenia. Platelets are coated with antibodies and these opsonized platelets are rapidly removed by phagocytes. On the other hand, therapeutic application of antibody concentrates (IVIg) rapidly raise platelet counts, and in some patients, sustained platelet recovery has been observed. The mechanism of action of IVIg is far from being clear. Several possible mechanism of action of IVIg treatment have been described. The immediate effect of IVIg seems to be a decrease in (unspecific) Fc mediated mononuclear phagocytosis, the long term effect might be a change in the complex network of the regulatory function of the immune response. Both types of interactions seem to play a keyrole in the immunomodulation. The various possible modes of actions evoke investigation of IVIg in a wide range of diseases with similar ineffective immune response. Controlled clinical studies have to be done to prove or disapprove the use of IVIg in other indications.

Autoimmune Diseases↗
PubMed1989

[Serum immunoglobulin concentrations in patients following bone marrow transplantation and preventive administration of high-dose nonspecific or normal-dose CMV-specific immunoglobulin].

Ten consecutive bone marrow transplant recipients were assigned alternatively to receive either a high dose polyspecific intravenous immunglobulin (HDIVIG) 0.5 g/kg weekly X 14, or a conventional dose of a CMV specific intravenous immunglobulin (CMVIG) 0.1 g/kg every three weeks. Before and after each application we determined the levels of total IgG, IgG subclasses, IgG 1, IgG 2, IgG 3, IgG 4, total IgA and IgM and of specific IgG and IgM antibody concentrations against endotoxin, lipid A, streptococcus A, hemophilus, EBV and CMV. In the HDIVIG, total IgG rose from 11 (median, range 2-11) g/l to 25 (22-32) g/l by day 89, in the CMVIG group, IgG dropped from 11 (10-15) g/l to 9 (6-12) g/l. In the same period the mean levels of IgG subclasses expressed as % of normal plasma pool increased in the HDIVIG group in all subclasses, not in the CMVIG group. The differences were significant, however, only for IgG 1 and IgG 2. IgG-antibodies against CMV, EBV, endotoxin, streptococcus and hemophilus did increase significantly in the HDIVIG group, but not in the CMVIG group. No increase was seen in both groups in lipid A antibodies and in specific IgM antibodies. Each application of CMVIG induced a transient increase of anti-CMV antibodies. We conclude that HDIVIG induces reproducibly an increase of specific and non-specific IgG antibodies. No attempt was made to assess clinical outcome. However, these results provide a rational basis for further therapeutic studies.

Adult↗
PubMed1989

[New indications for the use of immunoglobulins].

In the present review we discuss new clinical indications for IVIG therapy. Presently, clinical studies are under way to examine the effect of IVIG in uncommon diseases such as intractable epilepsy in children, myastenia gravis and necrotizing hemorrhagic enteritis. These considerable efforts in clinical research will most likely lead to new established indications for the use of IVIG.

Autoimmune Diseases↗
PubMed1989

Neutrophil chemiluminescence induced by opsonized group A streptococcal particles: an effective probe of intravenous immunoglobulin preparations.

We compared the capacity of eight different intravenous immunoglobulin (IVIG) preparations to opsonize streptococcal group A particles and to induce luminol-enhanced chemiluminescence in neutrophil granulocytes. Antibodies to the streptococcal group A carbohydrate (A-CHO) antigen exposed on the particles were present in all preparations at high concentrations. In some preparations, anti-A-CHO consisted predominantly of either immunoglobulin G1 (IgG1) or IgG2, whereas in others, both IgG subclasses were equally represented. Dilutions of the IVIGs and of a normal IgG reference preparation were adjusted for their anti-A-CHO content, incubated with streptococcal particles, and exposed to neutrophil granulocytes isolated from normal blood. The various IVIGs differed in their capacity to elicit chemiluminescence signals. Some preparations, particularly those consisting of chemically modified IgG molecules, showed little activity, whereas others were comparable to the reference preparation. We concluded that to some extent such differences could be related to the IgG subclass composition of the antibody. However, of greater importance were the manufacturing procedures by which both the antigen-binding fragment and crystallizable fragment portions, and thus the functional integrity of the IgG molecules, were more or less severely affected.

Humans↗
PubMed1988

Intravenous immune globulin in symptomatic paediatric human immunodeficiency virus infection.

Seven paediatric patients with symptomatic human immunodeficiency virus (HIV) infection were prospectively studied for 6-24 months after the start of intravenous immune globulin (IVIG) therapy. There was substantial clinical benefit during IVIG treatment with marked reduction of febrile and infectious episodes, normalization of physical and psychomotor development, and absence of mortality. The immunologic monitoring revealed some discrete objective improvements. The results of this study favourably compare to previous reports. It is concluded that IVIG should be standard therapy for symptomatic childhood HIV infection.

AIDS-Related Complex↗
PubMed1988

Primary immunodeficiencies in Switzerland: first report of the national registry in adults and children.

This first report of a Swiss registry includes 313 patients with primary immunodeficiency syndromes (PIDS) who were observed between January 1975 and January 1985. Diagnosis of specific PIDS was made according to WHO criteria. The most frequent disorders were IgA deficiency (33%) and common variable immunodeficiency (22%), followed by selective deficiency of other immunoglobulin isotypes (9%), severe combined immunodeficiency (9%), infantile sex-linked agammaglobulinemia (7%), and Wiskott-Aldrich syndrome (6%). Frequencies of other types of PIDS varied between 0.3 and 4%. Half of the patients were in the pediatric age group. Male patients predominated (63%). In addition to respiratory and urogenital tract infections, autoimmune disorders were observed in 14 patients with IgA deficiency or common variable immunodeficiency. IgA deficiency was, furthermore, associated with atopic and neurological disorders. A comparison with other national registries revealed some differences: the frequency of severe combined immunodeficiency was high (incidence, 24.3 cases per 10(6) live births), and that of ataxia teleangiectasia was particularly low (1.4 per 10(6) live births) in Switzerland. Frequencies of the three major PIDS groups of (i) predominantly antibody defects, (ii) predominantly cell-mediated defects, and (iii) PIDS associated with other major defects agreed with those reported in the other European studies.

Adolescent↗
PubMed1988

Monomeric and dimeric IgG1 as probes for assessing high-affinity and low-affinity receptors for IgG on human monocyte-derived macrophages and on activated macrophages.

From a panel of IgG1 myeloma proteins, only one was found to interact with human monocyte FcR in a manner similar to that of polyclonal IgG. This protein was used in binding studies involving human macrophage Fc receptors. A monomeric fraction depleted of dimeric and polymeric IgG1 was crosslinked with bis-diazonium benzidine, and a fraction highly enriched in cross linked IgG1 dimers was radiolabeled. Labeled monomeric and dimeric IgG were allowed to interact with monocytes that had matured to macrophages in vitro. The association with macrophages at 4 degrees C, in the presence of cytochalasin B, reached a plateau after 6 hr. The dissociation induced by excess unlabeled IgG followed similar kinetics as the association, but 20-30% of the bound IgG could not be dissociated. Under equilibrium conditions, evidence for a single FcR population binding monomeric IgG was obtained, the Kd being in the range of 12-42 nM. In contrast, the binding of dimeric IgG was more consistent with a model assuming two populations of binding sites when appropriate curve-fitting calculations were applied. The high-affinity FcR population had a Kd in the range of 0.8-3.5 nM, whereas the Kd of the low-affinity FcR population was in the range of 28-85 nM. When macrophages had been pre-treated with recombinant interferon-gamma, the expression of high-affinity sites was increased by a factor of 1.5-3, but the number of low-affinity sites was not augmented. Cytofluorographic analyses confirmed the increased expression of high-affinity FcR, binding fluoresceinating murine IgG2a. The expression of CD16, a low-affinity FcR expressed on neutrophils, NK cells and macrophages, as well as the expression of the complement receptor type III was little influenced by the rIFN-gamma pretreatment.

Antibody Affinity↗
PubMed1988

Prophylactic and therapeutic use of immunoglobulin for intravenous administration in patients with secondary immunodeficiencies associated with malignancies.

Failure of host defense systems associated with malignancies may be attributable to the tumor, to cytoreductive therapy or to combined endogenous and iatrogenic influences. Management of the resulting increased susceptibility to infections may require supplementation of antibiotic therapy with additional forms of treatment, including passive immunization with antibodies. This review discusses the use of immunoglobulin preparations for intravenous administration (IVIG) in patients with secondary immunodeficiencies associated with neoplasia. A suitable model for evaluating the prophylactic effect of IVIG is chronic lymphocytic leukemia. Many observations suggest that IVIG reduces the frequency of acute respiratory infections. Another malignant condition with decreased serum levels of polyclonal immunoglobulins and high frequency of infections is multiple myeloma. A crossover study recently demonstrated that IVIG significantly (P less than 0.01) reduced the frequency of respiratory tract infections in these patients. Furthermore the prophylactic effect of IVIG was evaluated in patients with small cell carcinoma of the lung. In a randomized prospective trial it was noticed that IVIG applied during intensive chemotherapy and irradiation courses significantly (P = 0.04) reduced the frequency of infections. Evidence for a therapeutic effect of IVIG was obtained in adult tumor patients and in children with leukemia or non-Hodgkin's lymphoma who developed severe varicella-zoster virus infections. The treatment effectively controlled fever, skin lesions and neuralgia and prevented progression of the infection. Therapeutic usefulness of IVIG in bacterial infections is still based on anecdotal evidence. Experimental data suggest that in addition to effects mediated by specific antibodies, nonspecific interactions of IgG molecules with Fc-receptors on macrophages may be clinically important.

Anti-Bacterial Agents↗