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Biomedical subjects

D C Heiner

Publications and source records attributed to D C Heiner.

At least 37 records · Page 2Linked to original sources

IgG subclass deficiencies: identifying and treating patients at risk.

IgG subclass deficiencies can increase the risk of pulmonary infections or other severe recurrent infections. Various groups of patients were studied in an attempt to learn more about (1) measuring the IgG subclass levels (particularly IgG4 levels) of possible high-risk patients; (2) identifying those patients who are at risk of developing recurrent infections, and (3) treating these patients once they have been identified. Individual cases are presented, and associations of isolated subclass deficiencies are examined with respect to infection. Replacement therapy with plasma or intravenous immunoglobulin (IVIG) to increase titers of deficient or absent subclasses is suggested.

Dysgammaglobulinemia↗

Class and subclass antibodies to Haemophilus influenzae type b capsule: comparison of invasive disease and natural exposure.

Recently, the role of immunoglobulin G (IgG) subclasses in the immune responses to organisms with polysaccharide capsules, particularly Haemophilus influenzae type b, has been of interest. We developed assays to measure IgG2- and IgG4-specific antibodies to the polyribosylribitol phosphate (PRP) polysaccharide antigen of H. influenzae type b and demonstrated that these assays were subclass specific. Relative levels of subclass-specific antibody were assayed in serum from 30 Alaskan Eskimo children who had invasive H. influenzae type b disease and 30 healthy controls that were matched for age and village of residence. We also measured total PRP antibody and total serum IgG4. The group with invasive H. influenzae type b disease had a significantly higher mean level of IgG4-specific PRP antibody than did the controls (P = 0.0006). However, we found no significant difference between cases and controls for IgG2-specific PRP antibody, total IgG4, or total PRP antibody. The data suggest that IgG4-specific PRP antibody is elicited by invasive H. influenzae type b disease, independent of age. The IgG4 subclass thus may be a critical determinant of the immune response to invasive infection caused by H. influenzae type b, especially for young infants who generally have a weak immune response to this organism.

Age Factors↗

IgG and IgG subclass specific antibody responses to diphtheria and tetanus toxoids in newborns and infants given DTP immunization.

To evaluate immune responses to diphtheria and tetanus toxoids in infants we used enzyme-linked immunosorbent assays to detect total IgG and specific IgG-1, IgG-2, IgG-3, and IgG-4 antibody. One group of infants received a newborn dose and subsequently received the usual three doses of DTP. A second group of infants received only the routine dosage at 2, 4, and 6 months of age. In sera acquired at birth, 6, and 9 months of age, there were no statistically significant differences between the two vaccine groups in IgG antibody responses to diphtheria or tetanus, or in IgG subclass tetanus-specific antibody responses. In individual children, tetanus-specific subclass responses were similar in pattern to that for total IgG tetanus antibody, i.e. each IgG subclass response appeared to be regulated by similar mechanisms in that child, but the regulation differed between children. In contrast to a prior study of pertussis immunity, maternally acquired antibody did not significantly affect immune responses to diphtheria or tetanus toxoid by 9 months of age. There was no discernible tolerance due to early tetanus or diphtheria immunization or to high levels of maternally acquired antibody.

Antibodies, Bacterial↗

Immunologic and clinical correlates of bronchial challenge responses to Bermuda grass pollen extracts.

We have studied 26 patients with asthma who had positive skin tests for Bermuda grass pollen antigen (BGP) with history, immunologic assays, and bronchial challenge with BGP. In these patients IgE anti-BGP RAST titers were higher in those with positive, 6.8 +/- 4.4% (mean +/- SEM) compared to those with negative bronchial challenges, 2.7 +/- 0.4% (p less than 0.02). Historical data did not predict bronchial challenge response. IgG4 anti-BGP RAST was not different in patients with positive and negative challenges but was markedly increased, 15.3 +/- 11.9%, in patients who had previously had BGP immunotherapy when compared to untreated patients, 3.6 +/- 5.1% (p less than 0.01). IgE anti-Bermuda grass appears to be the major contributor to susceptibility to BGP bronchial challenge. IgG4 anti-Bermuda grass is apparently unrelated to the sensitivity to challenge but appears to be a significant component of the immunologic response to immunotherapy.

Antibodies, Anti-Idiotypic↗

A common pathway for chemical-induced tissue injury and immune responses leading to hypersensitivity and/or carcinogenesis.

A common requirement for chemical-induced allergy, carcinogenesis and certain forms of liver injury appears to be the ability of the chemical to react with protein and/or nucleic acid to form covalent conjugates. Tests to detect immune responses to such conjugates can provide useful information concerning the propensity of an individual to convert normally innocuous chemicals to immuno-reactive forms under physiological conditions and may provide an indicator of the risk for developing one of the above disorders. They will enable offending substances and their active metabolites to be identified, the status of diseases which they induce determined, and the degree to which exposure has been avoided monitored. Very few studies have been published relating to this important problem. Implications of this approach are discussed.

Animals↗

IgD in human colostrum.

Simultaneous colostrum (C) and plasma samples (P) from 14 women, 1 to 5 days postpartum, were examined. Total IgD and specific IgD antibodies to beta-lactoglobulin, bovine serum albumin, Bermuda grass, and alpha-gliadin were measured by solid phase radioimmunoassay. The geometric mean concentrations of IgD were 35.8 (range 2.2-410) micrograms/dl for colostrum and 591.3 (range 72-4100) micrograms/dl for plasma. Six subjects had a specific IgD antibody C/P ratio more than 10-fold greater than the total IgD C/P ratio, suggesting enhancement of antibody to a specific antigen in the mammary gland. All six had C/P ratios suggestive of local enhancement of IgD antibody to Bermuda grass, and two met this criterion for enhancement of IgD antibodies to beta-lactoglobulin, bovine serum albumin, or alpha-gliadin. Specimens for these studies were obtained during the peak grass pollen season. Seventeen additional subjects were studied to compare total IgD in colostrum and plasma with total IgG and serum albumin. The mean C/P ratio for IgD (0.055 +/- 0.015) exceeded the C/P ratio for total IgG (0.015 +/- 0.003) or total albumin (0.020 +/- 0.002). For 14 of 17 subjects the colostrum/plasma ratio for IgD exceeded the C/P ratio for albumin or IgG. Data were transformed logarithmically and correlation coefficients calculated. For albumin versus IgG in colostrum, there was a strong correlation, r = 0.865, p = 0.001. This was different from albumin versus IgD, r = 0.489, p = 0.046 and from IgD versus IgG, r = 0.556, p = 0.020. These analyses support a different mechanism of entry of IgD into milk compared to IgG or albumin.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibody Formation↗

Increased serum IgG4 levels in acute Epstein-Barr viral mononucleosis.

Changes in serum IgG4 levels during heterophil-positive infectious mononucleosis were recorded. Pre-illness serial acute and convalescent specimens were evaluated. Mean IgG4 levels increased by 75% during acute infectious mononucleosis, reached a peak 21/2 to 3 weeks post-onset, and declined to baseline by 60 days. IgG4 peaked independently of other immunoglobulin classes.

Adolescent↗

Experience with an elemental diet (Vivonex).

Six patients with intractable atopic dermatitis completed this study which consisted of a baseline week, 1 to 2 weeks on an elemental diet, then sequential specific food additions. Symptom/sign scores, total eosinophil counts, and IgE and IgG4 radioimmunoassays for wheat alpha-gliadin, bovine serum albumin, beta-lactoglobulin, and egg white were carried out as part of the protocol. Symptom/sign scores improved in five of six patients, some dramatically. Total eosinophil counts generally dropped after a week on the elemental diet and then increased as foods were added to the diet. The elemental diet used (Vivonex) appears to be beneficial in the management of at least some adult patients who have severe atopic dermatitis.

Adolescent↗

Significance of immunoglobulin G subclasses.

IgG subclasses differ from one another both immunochemically and functionally. An isolated absence of a certain specific subclass may or may not be associated with disease. However, an absence of serum IgG4 as measured by a sensitive radioimmunoassay is usually, if not always, associated with severe recurrent pyogenic infections, usually of the respiratory tract. IgG2 and IgG4 deficiencies tends to occur together, often in association with deficiencies of immunoglobulin A (IgA) and/or immunoglobulin E (IgE). The properties of IgG1 are similar to those of IgG3 and those of IgG2 appear to resemble those of IgG4 in certain respects. Specific combined deficiencies tend to be associated with certain diseases. Some patients with deficiency of an immunoglobulin G (IgG) subclass appear able to compensate and to avoid clinical disease whereas others are not. Overlap zones exist in the lower ranges of serum concentrations in which both healthy and immunoincompetent subjects are found. It is important to consider the concentration of each IgG subclass present in a gamma globulin preparation or in plasma used for replacement therapy. If specific antibody deficiencies exist, it may be critical that the preparation used for replacement contains goodly amounts of the missing antibodies.

Ataxia Telangiectasia↗

Immunoglobulin G and M composition of naturally occurring antibody to type III group B streptococci.

Human sera were examined by an enzyme-linked immunosorbent assay for immunoglobulin G (IgG) and IgM antibodies to purified type III polysaccharide of group B streptococci. The antigen-binding capacity of a reference human serum was determined by a radioimmunoassay, and the total antibody content was determined by quantitative precipitation. The serum was then depleted of IgM and IgA to determine the effect on the antigen-binding capacity. Duplicate samples of 81 sera were tested by the enzyme-linked assay in comparison with reference standard serum. Although levels of IgG antibody were greater in subjects who had carried type III streptococci during pregnancy, concentrations of this antibody were generally low. Only 2 of 28 sera (7%) from parturient subjects and 7 of 25 sera (28%) from adult volunteers contained greater than or equal to 1 microgram of IgG antibody per ml; the mean levels were 0.13 and 0.53 micrograms/ml, respectively. In contrast, 19 of 28 maternal sera (68%) and 22 of 25 (88%) volunteer adult sera contained greater than or equal to 1 microgram/ml of IgM antibody; mean levels were 1.33 and 1.54 micrograms/ml, respectively. The cord serum levels of IgG antibody were almost identical to maternal serum concentrations, whereas IgM antibody was essentially undetected.

Antibodies, Bacterial↗

Enzyme-linked immunosorbent assay for the diagnosis of cerebral cysticercosis.

Central nervous system cysticercosis is common in countries where Taenia solium occurs in pigs and the level of hygiene and sanitation is low. The clinical presentation may include epileptic seizures, focal neurological deficits, hydrocephalus, or aseptic meningitis. The disease is frequently seen in California residents of Hispanic origin. It sometimes occurs in whites from homes that employ Hispanic cooks. Diagnosis is often difficult. Computerized tomography scan and brain biopsy are the most reliable diagnostic procedures, but each has its limitations. We have found that a radioimmunoassay improves our diagnostic capability, and more recently we have adapted this to an enzyme-linked immunosorbent assay that is equally sensitive and specific and, in addition, obviates the need for radioactive materials. Details of the enzyme-linked immunosorbent assay procedure and its application to the diagnosis of central nervous system cysticercosis form the basis of this report.

Animals↗

Sequential changes of the five immunoglobulin classes and other responses in infectious mononucleosis.

Serum total IgG, IgA, IgM, IgD, and IgE concentrations, heterophil antibody titer, Epstein-Barr virus (EBV)-specific antibodies titer, and hematologic changes were studied longitudinally in 19 patients with EBV-induced infectious mononucleosis who were followed up for 1.5-34 months. In 9 patients, the changes in these variables were compared with baseline data on a pre-illness serum sample. All 5 immunoglobulins (Ig) showed a significant rise during the acute illness followed by a drop during convalescence, and a gradual 'normalization' within several months to a year. On the average, IgE peaked to 276% during the first week, IgM to 176% at about 10 days, IgA to 154% at 15-20 days, IgG to 135% at 10-15 days, and IgD to 141% during the first 2 months after onset. IgE and IgM levels were significantly suppressed during convalescence by an average of about 40 and 25% of pre-illness level, respectively. A relationship was noted between Ig rise and the increase in circulating atypical lymphocytes. The data clearly demonstrate the polyclonal nature of Ig production during the acute phase of EBV-induced mononucleosis, with a striking and early reactivity of IgE.

Acute Disease↗