Impaired immunity: a view of current stigmata and disease evaluation.
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Autoimmune Diseases↗
Biomedical subjects
S D Litwin
Publications and source records attributed to S D Litwin.
Characteristics of suppressor cell activity appearing in cocultures of two individuals with immunodeficiency with thymoma.
Suppressor cell activity in two individuals (S1 and S2) with immunodeficiency with thymoma (ID-THY) was studied in peripheral blood mononuclear cells in pokeweed mitogen-stimulated single culture and cocultures. Secreted Ig was measured by radioincorporation and immunoprecipitation after 5-7 days. Control cocultures of normal/normal cells showed, in most cases, a percentage observed to expected ratio (% O/E) of cpm Ig near 100%. However, augmentation (% of O/E > 150) was often encountered, whereas suppression (% O/E < 50) was found only once in forty-two cocultures. In ID-THY/normal cell cocultures the degree of suppression by ID-THY cells varied widely when the same or different cocultivants were retested. This finding could be explained in part by an inverse correlation between the amount of secreted Ig produced by normal cells in single culture and the degree of suppression of the same normal by ID-THY cells in cocultures. A panel of normal cells were all suppressed when a range of S1 or S2/normal cell ratios were tested, weighing against genetic differences in suppressibility in the above system. ID-THY cells failed to block Ig secretion of human lymphoblastoid line cells, suggesting that the mechanism of suppression was related to a block in differentiation rather than interference with Ig synthesis per se. An experiment using cocultivants separated by a Millipore membrane showed that suppression was mediated by a humoral factor.
Adult↗
Effect of glucocorticoids on fetal immunoglobulin production after premature rupture of membranes.
Cord blood IgA and IgM levels were measured in newborns of mothers with prematurely ruptured membranes (PRM) who had also received prenatal glucocorticoid treatment to accelerate fetal lung maturity. Previous data show that some newborns of mothers with PRM had elevated IgA and/or IgM levels. This increase was also found in the present glucocorticoid-treated group, indicating that glucocorticoid therapy did not appear to alter fetal humoral immune response at all.
Betamethasone↗
The relationship between prematurely ruptured membranes and fetal immunoglobulin production.
Cord blood and maternal sera were studied in a series of 227 cases of prematurely ruptured membranes (PRM) with respect to: (1) fetal immunoglobulin (lg) synthesis associated with PRM, (2) the interrelationship between different lg classes during infection, and (3) the relationship between lg values and the duration of PRM prior to the onset of labor. A preliminary report from this laboratory, which indicated that a humorla fetal immune response occurred in some but not all cases of PRM, and that significant increases in either IgA or IgM could be found, was confirmed. There was both clinical and immunologic evidence of one peak of infection one to 12 hours after onset of PRM and another after 72 hours after onset of PRM, suggesting that some patients were infected before the clinical onset of PRM symptomatology. Increased IgA and/or IgM was found in 16.3% of infants with clinical evidence of infection. This was comparable to the 18.5% of patients with PRM who had elevated IgA and/or IgM without clinical evidence of infection. Further, there was no correlation between the severity of infection and the presence of lg elevation. Based on the data in the present series, lg determination in cord blood cannot be used to distinguish cases of PRM with and without fetal infection.
Bacteria↗
Life history of mouse sperm protein. Intratesticular stages.
A basic protein fraction, migrating as a single band in acetic acid-urea gel, distinct from histones, was isolated from mouse sperm collected from vasa deferentia and caudae epididymides and was used to immunize female rabbits. The presence of antibodies to the mouse sperm protein (MSP) in the rabbit antisera was demonstrated by a cytoimmunofluorescence procedure using the cells of origin of the antigenic protein, the mature mouse sperm. The specificity of the antisera was verified by fluid and gel precipitation tests and by crossed immunoelectrophoresis. The latter procedure demonstrated the presence of two antigen-antibody systems, consonant with earlier reports that the basic chromosomal protein of mouse sperm is heterogeneous. MSP antigen in situ was recognized by the specific antibodies of the rabbit antisera only after the smear of mature sperm was treated with either of two reducing agents: 2-mercaptoethanol or dithiothreitol. However, when the immunofluorescence procedure was applied to untreated smears of mouse testicular cells, spermatids of all stages from 1 to 14-15 were positive, while spermatocytes, stage 16 spermatids and spermatozoa were negative. After treatment of testes smears with reducing agent, only spermatocytes remained negative. Those observations indicate the following: (a) MSP is immunogenic in a heterologous species; (b) its antigenic sites are detectable in spermatozoa and spermatids of all stages, but not in primary spermatocytes; (c) those antigenic sites become masked at about stage 15 of spermiogenesis and may be unmasked by treatment with a reducing agent. The interpretation is made, therefore, that one or more components of MSP are assembled at the beginning of spermiogenesis and undergo an alteration in the final intratesticular stage of spermatid maturation. That alteration may be presumed to be the formation of disulfide linkages between the cysteine residues.
Animals↗
Immunodeficiency with thymoma: failure to induce Ig production in immunodeficient lymphocytes cocultured with normal T cells.
Blood mononuclear cells of two individuals having immunodeficiency with thymoma (ID-THY) were cocultured with normal mononuclear cells or treated mononuclear cell fractions in an attempt to correct an imbalance of regulatory cells postulated to be responsible for the failure of pokeweed mitogen-induced Ig synthesis in vitro. Treatment included abrogation of suppressor cell activity by irradiation or incubation with prednisilone in vitro. T cell help was provided by cocultivating lymphocytes of related and unrelated persons, and in some cases autologous treated cells. Ig secretion failed to be induced by any experimental maneuver suggesting that the primary problem in the above ID-THY cells was related to defective or deficient B cells rather than an imbalance of T regulatory cells. Prednisilone treatment in vitro decreased suppressor cell activity in allogeneic cocultures of two ID-THY persons (S1 and S2) but not of an individual (S3) with variable immunodeficiency suggesting heterogeneity of suppressor cells.
Animals↗
The effect of fetal age, birth weight, and sex on cord blood immunoglobulin values.
In order to determine the role played by fetal "factors" in fetal immunoglobulin levels, cord blood samples from 176 normal infants were analyzed for the relationship between immunoglobulin concentration and the gestational age, birth weight, and the sex of the fetus. Cord blood IgM and IgG both increased with gestational age until term, while IgA, its subclasses IgA, and IgA2, and IgD were unaffected by gestational age. IgM and IgG were higher in fetuses weighing 2,000 grams or more, while IgA, IgA, and IgA2 were not influenced by birth weight. Cord blood immunoglobulin values were the same in male and female infants. The interrelationship between cord blood immunoglobulin class and subclass concentrations was examined in two ways: (1) The correlation coefficient r for paired samples was calculated between immunoglobulin concentrations in individual cord sera. (2) Student's test for the mean was used to compare subgroups of the entire sample populations, divided into high, intermediate, and low immunoglobulin values. IgM and IgG, and IgM and IgD were correlated. The data obtained indicate the need to consider the gestational age and birth weight of a neonate in the use of cord blood immunoglobulin values to evaluate the possibility of fetal infection.
Birth Weight↗
Detectability and pattern of immunoglobulins in normal amniotic fluid throughout gestation.
Immunoglobulin (Ig) M, IgA, and IgD class and IgA, and IgA2 subclass levels were detected in normal amniotic fluid throughout gestation with a hemagglutination-inhibition assay: IgG was measured by single radial immunodiffusion. In 161 tested samples, IgA, IgA, IgA2, and IgG were measurable in all cases; IgM was measurable in 99.4 per cent and IgD, in 90.6 per cent of the fluids. IgA, IgG, and IgD concentrations increased toward midpregnancy and thereafter decreased to term in a pattern similar to that for amniotic fluid total protein. IgM, on the other hand, remained relatively constant through week 35 of gestation; thereafter, it increased to term. There was no correlation in this normal group between amniotic fluid and cord blood levels of Ig class or subclass at term. Mean IgA values were 2.2 times higher in amniotic fluid than in cord serum. This was in sharp contrast to IgM, which was 16 times higher, IgG, which was 66 times higher, and IgD, which was 2.4 times higher in cord serum than in amniotic fluid. The inverse data for IgA as compared to other Ig classes suggest that amniotic fluid IgA may be partially derived from IgA in fetal gastrointestinal and pulmonary secretions. Determination of the concentration of the different Ig classes (and eventually subclasses) in amniotic fluid may be useful in diagnosis of intrauterine infections, malformations, and immunodeficiencies.
Amniotic Fluid↗
Fetal immunoglobulin production following prenatal glucocorticoid treatment.
In order to accelerate fetal lung maturation 46 pregnant women were given either dexamethasone or betamethasone intramuscularly during 3 consecutive days during 29--36 weeks of gestation. At birth, the infants appeared to have intact humoral immune function in that they could produce normal amounts of immunoglobulins in utero, and 2 fetuses responded with increased synthesis of IgA or IgM following premature rupture of the membranes. The clinical course did not show any increased incidence of puerperal or neonatal illness attributable to intrauterine infection.
Betamethasone↗
Fetal immunoglobulin synthesis following maternal immunosuppression.
Cord blood levels of immunoglobulin (Ig) A, IgM, IgD, and IgG classes and IgA and IgA subclasses were determined in the offspring of seven mothers who received azathioprine and/or prednisone during the entire pregnancy. Five of these women received the immunosuppressive therapy following kidney transplantation, and two received immunosuppressive therapy because of disseminated systemic lupus erythematosus. The fetuses appeared to have intact humeral immune function in that they had normal cord blood immunoglobulin concentrations and in one case responded with increased synthesis of IgA and IgM following premature rupture of the membranes.
Adult↗
Differentiation of human lymphocytes by pokeweed mitogen in vitro: studies in normal and in immunodeficient subjects.
Immunoglobulin (Ig) synthesis and secretion by peripheral blood lymphocytes activated by pokeweed mitogen (PWM), and by phytohemagglutinin (PHA) was measured in normal individuals and in subjects with primary immunodeficiency. Unstimulated cultures demonstrated stable, low Ig synthesis of all major Ig classes; PWM showed a peak of Ig synthesis at day 5; PHA cultures demonstrated a late peak of ig production at day 9. Three cases of common variable immunodeficiency showed different patterns of data when the percentage of B cells in blood and Ig production in vitro were used as parameters. Two persons with immunodeficiency and thymoma showed decreased Ig production in vitro, and had suppressor cells capable of blocking Ig production by normal lymphocytes in co-cultivation experments.
Aged↗
Prenatal diagnosis of congenital rubella.
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Adolescent↗
Lymphocytes suppressing both immunoglobulin production and erythroid differentiation in hypogammaglobulinaemia.
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Agammaglobulinemia↗
Prenatal diagnosis of congenital rubella.
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Adolescent↗
IgD and the fetal immune response.
IgD was detected in 84% of cord sera at term by an inhibition-of-hemagglutination test, in contrast to low incidences reported earlier. Cord blood IgD and maternal serum IgD values were unrelated to each other, consistent with a fetal origin of the IgD. The cord blood IgD failed to correlate, either directly or inversely, with cord blood IgA or IgM, suggesting that its presence does not reflect fetal synthesis of specific antibody but rather may be developmental.
Antibody Formation↗
Partially restricted antitoxins of tetanus and diphtheria in man.
Antibodies of restricted specificity have been identified in the human in response to certain antigens. The present study analyzed tetanus and diphtheria antitoxins isolated from selected human sera and suggested a restricted response in antibody production to each of these antigens. Purified antibodies from eight serum specimens with elevated hemagglutination titers to tetanus and four to diphtheria yielded only IgG proteins in concentrations of 160-500 microgram/ml. Although some of the tetanus specimens were derived from cord sera and tetanus immunoglobulin, none of the total group had antibodies of the IgA and IgM classes. Utilizing immunoelectrophoresis against heavy chain subclasses, genetic markers, and kappa and lambda quantitations, a predeliction for the kappa IgG1 subclass was established for both tetanus and diphtheria antibodies. The lambda light chains were present in diminished quantities, IgG2 heavy chains were absent, and the IgG3 and IgG4 chains were variably identified.
Antibody Specificity↗
Fetal immune response following congenital toxoplasmosis.
Serum concentrations of IgA, its subgroups IgA1 and IgA2, IgM, IgG, and IgD were determined in a group of 14 mothers who contracted toxoplasmosis during pregnancy and their 14 offspring. Four newborns developed toxoplasmosis, 10 did not. The 4 infants with congenital toxoplasmosis had evidence of increased immunoglobulin synthesis in utero in sharp contrast to the 10 offspring of toxoplasmosis-infected mothers who failed to develop the disease. Three of these 4 affected children had elevated IgM levels; all 4 had significantly increased IgA values. The use of IgA subclass IgA1 and IgA2 was not helpful in distinguishing infants with congenital toxoplasmosis from unaffected infants. The present series is consistent with other studies from this laboratory, indicating that the fetal immune response to intrauterine infection may include IgA as well as IgM.
Adult↗
Fetal immune response following prematurely ruptured membranes.
Concentrations of immunoglobulins (Ig)A1, and IgA2, IgD, IgE, IgG, and IgM have been determined in cord blood, amniotic fluid, and maternal serum in a group of patients with a history of prematurely ruptured membranes (PRM) prior to the onset of labor and in a control group of patients undergoing normal delivery and without a history of infection during pregnancy. IgA and IgD were determined by sensitive hemagglutination-inhibition tests; IgG and IgM, by radial immunodiffusion; IgE, by a radioimmunoassay. There was evidence for an immune response in 10 of 16 cases of PRM: five of 16 had increased IgA but normal IgM; three of 16 had increased IgA and IgM; two of 16 had high IgM and normal IgA in cord blood. In patients with significantly increased levels of either IgA or IgM or both, there was a decreased level of IgD. These changes are most likely the result of the immune response to ascending infection from the maternal genitals. The sensitive testing method employed could demonstrate the presence of IgD in 53 per cent of normal cord blood samples and 72 per cent of amniotic fluid samples obtained at term. IgE was found in all normal cord blood and amniotic fluid samples tested. By concentrating the amniotic fluid up to 180-fold, IgM was demonstrated in all normal samples tested. The potential importance of IgA determinations in cord blood in addition to IgM determination for detection of intrauterine infections is stressed.
Amniotic Fluid↗