Martha Sun

The Development of Respiratory Syncytial Virus-Specific IgE and the Release of Histamine in Nasopharyngeal Secretions after Infection

We studied the development of respiratory syncytial virus (RSV)-specific IgE and the release of histamine in nasopharyngeal secretions from 79 infants with various forms of respiratory illness due to RSV. RSV-IgE was measured by an enzyme-linked immunosorbent assay; specificity was confirmed by appropriate blocking experiments. Histamine content in the secretions was determined by fluorimetric methods. RSV-IgE was detectable in only one of 19 patients with RSV infection without wheezing, but was detectable in the majority of 60 patients with wheezing (P less than 0.01). Titers of RSV-IgE were significantly higher in patients with wheezing (P less than 0.05). Histamine was detectable in secretions of some patients with all forms of illness but was detected significantly more often (P = 0.05) and in higher concentrations in patients with wheezing. Peak titers of RSV-IgE and concentrations of histamine correlated significantly with the degree of hypoxia (P less than 0.001). Formation of RSV-specific IgE and release of histamine may adversely affect the outcome of RSV infection.

Predictive value of respiratory syncytial virus-specific IgE responses for recurrent wheezing following bronchiolitis

To determine whether the magnitude of the respiratory syncytial virus (RSV)-specific IgE response at the time of an episode of RSV bronchiolitis in infancy accurately predicts the development of subsequent wheezing episodes, we observed 38 infants prospectively from the time of an episode of infantile bronchiolitis through 48 months of age. Peak RSV-IgE titers were measured at the time of the bronchiolitis episode using an ELISA procedure. Notation was made of both the number of subsequent wheezing episodes reported by parents and the number documented by a physician. Subsequent wheezing was documented by a physician in 20% of infants who did not develop an RSV-IgE response at the time of the bronchiolitis episode and in 70% of those with the highest responses (P less than 0.025). These results suggest that the magnitude of the RSV-IgE response at the time of RSV bronchiolitis is a useful prognostic indicator for recurrent wheezing.

Role of parainfluenza virus-specific IgE in pathogenesis of croup and wheezing subsequent to infection

In order to determine the role of parainfluenza virus-specific IgE antibody production and release of histamine in the pathogenesis of lower respiratory disease caused by parainfluenza virus infection, we studied 84 infants and children at the time of parainfluenza virus infection. Parainfluenza virus-IgE antibody was detected in samples of nasopharyngeal secretions by means of an enzyme-linked immunosorbent assay, and histamine content of nasopharyngeal secretions was determined by a fluorometric technique. Virus-specific IgE responses appeared earlier and were of greater magnitude in patients with croup, wheezing, and croup with wheezing caused by parainfluenza virus infection than in patients with parainfluenza virus-induced upper respiratory illness. Histamine was detectable in nasopharyngeal secretions of patients with parainfluenza virus-related croup significantly more often than in patients with upper respiratory illness caused by parainfluenza virus. These observations suggest a role for immunologic mechanisms in the pathogenesis of severe forms of respiratory illness caused by parainfluenza virus infection.

The antibody response to primary and secondary infection with respiratory syncytial virus: Kinetics of class-specific responses

Serum antibody responses to primary and secondary infections with respiratory syncytial virus were determined in 67 hospitalized infants. Responses in IgG, IgM, and IgA immunoglobulin fractions were assayed using an indirect immunofluorescent technique. Infection was confirmed by identification of RSV antigen in nasopharyngeal secretions using indirect immunofluorescence, and by recovery of the virus in tissue culture. IgM specific antibody response was commonly observed within a few days of onset of primary infection and persisted from two to ten weeks. Increases in titer of virus-specific IgG and IgA were observed in infants aged 6 months or more at the time of infection than in younger infants. At one year after primary infection, IgA and IgM specific antibody was undetectable, and IgG antibody was absent or present in low titer. Subsequent reinfection result ed in accelerated antibody response in all three classes of serum immunoglobulin. High titers of RSV-specific IgG, IgM, and IgA antibody were detectable at five and seven days after reinfection. These observations may explain the relatively mild nature of clinical illness associated with RSV reinfections in childhood.

Respiratory Syncytial Virus-Specific IgE Responses following Infection: Evidence for a Predominantly Mucosal Response

ABSTRACT: In order to determine whether IgE production occurs predominantly at mucosal or systemic sites, we studied the production of respiratory syncytial virus (RSV)- specific antibody in serum and nasopharyngeal secretions (NPS) from 41 patients with RSV infection using an enzyme- linked immunosorbent assay. RSV-IgE was found in higher titer in samples of NPS than in simultaneously obtained serum specimens at all phases of illness. Despite the excess dilution incurred in the collection process, RSVIgE was frequently detected in NPS specimens while it was undetectable in serum. In 20 selected subjects, ratios of RSV antibody in NPSrserum were 2.00 for RSV-IgE, 2.42 for RSV-IgA, and 0.01 for RSV-IgG. Also the geometric mean value of ratios of RSV-IgE:RSV-IgG was 1.74 in NPS and 0.05 in serum, while the geometric mean value of ratios of RSV-IgA:RSV-IgG were 1.85 in NPS and 0.09 in serum. These data suggest that IgE production occurs predominantly at mucosal surfaces.

Defective Regulation of Immune Responses in Croup Due to Parainfluenza Virus

ABSTRACT: In order to determine if defects in regulation of immune responses play a role in the pathogenesis of croup, we studied 37 infants and children with either croup or upper respiratory illness alone due to parainfluenza virus (PV). PV-specific IgE responses were determined by an enzyme-linked immunosorbent assay, cell-mediated immune responses to PV antigen were studied by in vitro lymphocyte transformation assays, and suppressor cell function was determined by addition of histamine to lymphocyte transformation assays. In comparison to patients with upper respiratory illness alone, patients with croup had increased production of PV-specific IgE antibody, increased lymphoproliferative responses to PV antigen, and diminished histamine-induced suppression of lymphocyte transformation responses to PV. These results suggest that a defect in suppressor function exists among croup patients. Similar defects have been demonstrated in bronchiolitis and atopic diseases, providing an immunologic link between the three illnesses.

1090 THE DEVELOPMENT OF RESPIRATORY SYNCYTIAL VIRUS (RSV) SPECIFIC IgE AND THE RELEASE OF HISTAMINE IN NASOPHARYNGEAL SECRETIONS FOLLOWING RSV INFECTION: POSSIBLE ROLE IN THE PATHOGENESIS OF BRONCHOSPASM

A group of 20 infants and children with acute infection with RSV were tested during the first week of illness for the appearance of RSV specific IgE and the presence of histamine in their nasopharyngeal secretions. The IgE antibody activity was determined by an enzyme linked immunosorbent assay (ELISA), using purified RSV and peroxidase-conjugated monospecific rabbit antisera to human IgE. The histamine concentrations were determined by the fluoremetric method. RSV specific IgE was detected in nasopharyngeal secretions of 57% of all infected subjects. 75% of patients with bronchiolitis associated with wheezing and 30% of RSV infected subjects without wheezing possessed RSV specific IgE in the nasopharyngeal secretions. Histamine activity was observed in the nasopharyngeal secretions of all RSV infected subjects Significantly, however, the individual and mean histamine content in the secretions of patients with bronchiolitis or wheezing was higher (P<0.01) than in subjects without any clinical bronchospasm. These observations suggest the development of RSV specific IgE and histamine release in the respiratory tract of many RSV infected subjects. It appears that the magnitude of IgE mediated histamine production in the respiratory tract may determine the form of clinical illness and the degree of bronchospasm during acute infection with RSV.