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Biomedical subjects

I Quinti

Publications and source records attributed to I Quinti.

At least 55 records · Page 3Linked to original sources

Presence of maternal antibodies to human immunodeficiency virus 1 envelope glycoprotein gp120 epitopes correlates with the uninfected status of children born to seropositive mothers.

The present study demonstrates that maternal antibodies to certain epitopes of human immunodeficiency virus 1 (HIV-1) proteins are associated with a defined outcome for at-risk pregnancies of HIV-infected women. An initial retrospective analysis of antibodies to synthetic peptides and recombinant proteins representing env, pol, and gag regions of HIV-1 was carried out. Sera studied were from 33 children who were born to HIV-infected mothers and whose clinical outcome was known at the time of analysis. Sera, collected within the first 6 months of life, of uninfected at-risk children were found to selectively contain maternal antibodies to certain peptides containing epitopes of the HIV envelope glycoprotein gp120. To confirm the predictive role of maternal antibodies to defined HIV-1 epitopes, a prospective analysis was then performed on sera from 21 HIV-seropositive mothers and their infants, whose clinical and immunological status was then followed up for a period of at least 15 months. As expected, antibodies to the same envelope protein peptides were detected almost exclusively in sera from mothers of uninfected children. Our data suggest that antibodies against select epitopes of HIV envelope protein gp120 might play an important role in preventing mother-to-child transmission of HIV-1 infection. Accordingly, site-directed serology might be used to predict the outcome of an at-risk pregnancy of an HIV-infected woman.

Amino Acid Sequence↗

IgG anti-IgE from atopic dermatitis induces mediator release from basophils and mast cells.

IgG antibodies containing anti-IgE activity isolated from a patient with atopic dermatitis (H-aIgE) induced mediator release from human basophils and mast cells isolated from skin and lung tissues. The release of histamine was calcium- and temperature-dependent and did not involve cytotoxicity. There was an excellent correlation (r = 0.88; p less than 0.001) between the maximum percent histamine release from human basophils induced by rabbit anti-IgE (R-aIgE) and H-aIgE. H-aIgE was approximately 30 times more potent than R-aIgE in inducing mediator release from human basophils, skin, and lung mast cells. H-aIgE specifically desensitized human basophils to a subsequent challenge with both H-aIgE and R-aIgE. Lactic acid removal of IgE from human basophils blocked the releasing activity of both R-aIgE and H-aIgE. Passive sensitization with hyperimmune sera or purified IgE myeloma restored the response of basophils to both R-aIgE and H-aIgE. IgE purified from three different myeloma patients concentration-dependently blocked the histamine releasing activity of both R-aIgE and H-aIgE.

Adolescent↗

Intestinal permeability and antigen absorption in rheumatoid arthritis. Effects of acetylsalicylic acid and sodium chromoglycate.

Intestinal permeability was measured using cow's milk beta-lactoglobulin absorption (BLG) as a permeability marker in 14 patients with active and inactive rheumatoid arthritis (RA) under three different conditions: after a washout period, after treatment with acetylsalicylic acid (ASA) associated with disodium chromoglycate (DSCG), and with ASA only. No intolerance to cow's milk was present and serum IgE levels were in the normal range in 12 of 14 patients. IgG anti-IgE were present in 7 of 13 patients tested. When off treatment the intestinal permeability to BLG in RA patients was not increased as compared to controls, but we found a significative difference between active and inactive RA. ASA administration strongly increased BLG absorption, not prevented by DSCG pretreatment. In normal controls treated with a single dose of ASA we obtained similar results. Our results suggest that prolonged treatment with nonsteroidal anti-inflammatory drugs induces an increase of food antigen absorption, apparently not related to anaphylaxis mediator release, with possible clinical effects.

Adult↗

Acquisition of Ig isotype diversity after bone marrow transplantation in adults. A recapitulation of normal B cell ontogeny.

To gain insight into the prolonged susceptibility to infections noted after allogeneic bone marrow transplantation (BMT), multiple parameters of the humoral immune system were serially monitored in ten bone marrow recipients. IgM B cells appeared in the circulation 2 to 4 mo after engraftment. During the first 6 mo, the IgM B cells expressed low levels of CD21 (C3d/EBV receptors) and were largely CD38+. IgG and IgA B cells were also found to coexpress surface IgM and IgD, indicating that they may be involved in a process of isotype switch. These features are characteristic of neonatal B cells. To explore the pattern of Ig isotype switch, the emergence of plasma cell precursors for each of the four IgG subclasses was examined by culturing blood lymphocytes with PWM or LPS and enumerating bone marrow plasma cells. A marked IgG2 and IgG4 plasma cell deficiency and a relative increase in IgG1 and IgG3 plasma cells were detected both in vitro and in vivo. Serum IgG2 and IgG4 levels were deficient for more than 18 mo after BMT, elevated IgG1 levels accounting for the normal or increased levels of total IgG. The data suggest that a selective unresponsiveness to polysaccharide Ag and IgG2 subclass deficiency may contribute to the late bacterial infections in BMT recipients. These features of gradual development of the humoral immune system in adults undergoing successful marrow engraftment reproduce some of the maturational steps that occur during normal B cell ontogeny over the first 1 to 2 yr of life.

Adolescent↗

Agenesis of the corpus callosum, combined immunodeficiency, bilateral cataract, and hypopigmentation in two brothers.

We describe 2 brothers with a malformation syndrome consisting of agenesis of the corpus callosum, cutaneous hypopigmentation, bilateral cataract, cleft lip and palate, and combined immunodeficiency. The clinical history of both patients was characterized by severe psychomotor retardation, seizures, recurrent severe respiratory infections, and chronic mucocutaneous candidiasis. The children died of bronchopneumonia at age 2 and 3 years, respectively. Immunological investigations showed, in one sib studied, skin anergy to recall antigens, profound depletion of T4+ lymphocytes, and serum IgG2 deficiency. Necropsy showed agenesis of the corpus callosum, hypoplasia of the cerebellar vermis, and profound hypoplasia of the thymus and of the peripheral lymphoid tissue. The distinctive features of these sibs appear to define a previously undescribed hereditary MCA/MR syndrome. The clinical and pathological findings seem to indicate, as a pathogenetic mechanism, a defect involving the embryonic organization of the central nervous system and of the immune system.

Abnormalities, Multiple↗

Studies on the in vitro effects of auto-anti-IgE. Inhibition of total and specific serum IgE detection by a human IgG autoantibody to IgE.

We isolated a human IgG anti IgE autoantibody by affinity chromatography on a myelomatous IgE (N.D.) coated Sepharose column, from the serum of a patient with atopic eczema, and probed its ability to inhibit IgE recognition by heteroantisera to IgE used in commonly available assays for serum total and specific IgE determinations (Paper radio-immunosorbent test--PRIST and Phadezym radioallergosorbent test--RAST, both from Pharmacia, Uppsala--Sweden). Our results indicate that IgG anti IgE decrease total IgE results by 10-90% according to its weight ratio to IgE molecules present in samples devoid of endogeneous anti-IgE. Sera with high content of specific IgE to house dust mite (RAST class 3 or 4) are less affected by this autoantibody, but RAST class 2 may be significantly lowered when purified IgG anti IgE is added. These data imply that anti IgE can affect both total and specific IgE determinations.

Allergens↗

IgG subclasses to food antigens.

Involvement of sub-classes of IgG that are specific for food allergens in anaphylactoid reactions and some manifestations of atopy no longer needs to be shown. Accordingly, sub-classes of IgG specific for ovalbumin (OVA) and beta-lactoglobulin (BLG) were compared in healthy subjects and those who presented with an intolerance or food allergy to OVA and BLG to decide whether a restrictive diet was necessary. The four sub-classes of IgG1, IgG2, IgG3 and IgG4 were isolated in all the groups. IgG4 was highest in the allergic subjects and the IgG sub-class values were modified by the diet differently in each group. Unfortunately, the small number of subjects does not allow the formation of a definite conclusion to this study.

Antigens↗

Evaluation of the presence of RF-like activities in immunoglobulin preparations for intravenous use. I. IgG anti-IgE in intravenous Ig.

We have studied the IgG anti-IgE antibody content of 8 IgG preparations for intravenous administration that we use in our Day Hospital as replacement therapy for patients with hypogammaglobulinemia. In all preparations we found the presence of both IgE and IgG anti-IgE as monomers and oligomers after fractionation with ultracentrifugation on sucrose gradient. This RF-like activity seem to be an essential constituent of low m.w. aggregates, disappearing at acid pH. We suggest that its presence could be responsible for the enrichment of IgE in Ig preparations for therapeutic use and perhaps for immediate and long-term adverse reactions.

Antibodies, Anti-Idiotypic↗

Evaluation of the presence of RF-like activities in immunoglobulin preparations for intravenous use. II. IgG and IgA anti-IgG in intravenous Ig.

IgG- and IgA-rheumatoid factor like activities have been found in 4 out of 8 i.v. Ig preparations and in 1 i.m. Ig studied as control. In 2 i.v. Igs as well as in the 1 i.m., these RF-like activities were both present. These RF-like activities seem to be essential constituents of low m.w. aggregates, disappearing at acid pH. Their presence could perhaps be responsible for the enrichment of IgA in Ig preparations for therapeutic use and theoretically for the side-effects occurring "in vivo" after injection.

Antibodies, Anti-Idiotypic↗

Hypogammaglobulinemia with hyper-IgM, severe T-cell defect, and abnormal recirculation of OKT4 lymphocytes in a girl with chronic lymphadenopathy.

We describe here one 8-year-old girl with an unusual form of immunodeficiency, characterized by hypogammaglobulinemia with hyper-IgM, severe T-cell defect, and chronic lymphadenopathy. Patient's B cells failed to produce IgG or IgA in vitro following stimulation with either pokeweed mitogen or Epstein-Barr virus, suggesting an intrinsic B-cell defect. Abnormal T-cell function was demonstrated by impaired in vivo delayed type hypersensitivity, reduction of mitogen-induced proliferation and interleukin 2 production, reduction of interferon-gamma production, and marked decrease of circulating OKT4+ cells. The latter cells were found in normal proportion in the patient's lymph node tissue. This finding suggests that the decrease of OKT4+ cells in peripheral blood was due to the abnormal recirculation of these cells. The identity of this syndrome with the infantile form of the acquired immunodeficiency syndrome was apparently ruled out by the failure to demonstrate HTLV-III-related sequences in patient's lymphocytes or virus-specific serum antibodies.

Agammaglobulinemia↗

Circulating IgG autoantibodies to IgE in atopic syndromes.

Sera from nonatopic healthy donors and patients with hyper-IgE syndrome, allergic respiratory disease, i.e., allergic rhinitis and asthma, and atopic dermatitis were assayed for the presence of IgG and IgM antibodies to IgE. The assay used was based on an ELISA method that measured the binding of IgG or IgM in test sera to myeloma IgE (PS)-coated microtiter wells. The levels of IgG anti-IgE but not of IgM anti-IgE were elevated in patient sera of all three categories tested. The same sera failed to demonstrate increased levels of IgG anti-IgM or IgG anti-IgA. Significant IgG anti-IgE activity remained after absorption of patient sera over pooled human IgG F(ab')2 Sepharose. The IgG anti-IgE activity appeared to be directed toward the Fc portion of IgE because absorption of positive sera over IgE (ADZ) Sepharose but not over myeloma IgG Sepharose completely removed their reactivity with IgE (PS) and because sera from atopic individuals but not from normal subjects contained IgG anti-IgE activity against the protein backbone of the Fc portion of IgE synthesized from a fragment of the cloned gene of human myeloma IgE (ND) heavy chain. Regression analysis demonstrated a weak but significant correlation (r = 0.31; p less than 0.05) between serum IgE levels and IgG anti-IgE activity. Fractionation of sera from the three patient categories by gel filtration over Sepharose 6B revealed that IgG anti-IgE activity was present both as monomeric IgG and in IgE containing immune complexes (IC). Intermediate molecular size IC (between 7S and 19S) were present in all three patient groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody Specificity↗

IgG anti-IgE in circulating immune complexes in the hyper-IgE syndrome.

We fractionated, by gel chromatography, sera with high IgE content from atopic subjects and five cases with the hyper-IgE syndrome, and measured the presence of IgE in high molecular weight (HMW) fractions. Two out of four asthmatics and four out of five hyper-IgE had HMW IgE. The same serum fractions gave positive results for conglutinin binding IgG (all six) and IgA (three cases) as well as C1q binding complexes (five cases). IgG auto-antibodies to IgE were also detected together with IgE in HMW fractions. Anti-F(ab)'2 activity was present in five cases (one of them negative for IgG anti-IgE). Our data indicate that complexes made of IgE and IgG anti-IgE are present mainly in patients with chronic allergic symptoms and most frequent in cases of hyper-IgE syndrome.

Antibodies↗