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Published on: December 10, 2013
Circulating polyribophosphate in Hemophilus influenzae, type b meningitis. Correlation with clinical course and
Insights
Polyribophosphate, released during Hemophilus influenzae type b infections, was measured in children with meningitis. Impaired clearance of this antigen correlated with severe symptoms and reduced antibody response, suggesting immune system deficiencies.
Area of Science:
- Pediatric Infectious Diseases
- Immunology
- Microbiology
Background:
- Hemophilus influenzae type b (Hib) meningitis releases polyribophosphate (PRP) into circulation.
- Understanding PRP clearance is crucial for managing Hib infections and immune responses.
Purpose of the Study:
- To quantify PRP in serum and cerebrospinal fluid of children with Hib meningitis.
- To investigate the relationship between PRP levels, clearance, clinical course, and antibody response.
Main Methods:
- Radiolabeled antigen-binding inhibition assay used for PRP quantification.
- Serial serum and CSF samples analyzed from 45 children with Hib meningitis.
- Radioimmunoassay employed to detect antipolyribophosphate antibody responses.
Main Results:
- PRP detected in acute serum and CSF; unbound form persisted 1-30 days post-therapy.
- Acid-labile PRP complexes found in serum up to 145 days.
- Prolonged antigenemia linked to protracted fever, neurological symptoms, and focal complications.
- 79% of patients developed antipolyribophosphate antibodies; intensity correlated with antigen clearance efficiency.
- Impaired antigen clearance associated with low antibody magnitude and potential immune deficiencies.
Conclusions:
- Antigen clearance mechanisms significantly influence humoral immune response development and intensity.
- Deficiencies in the PRP clearance system may occur in infants and children.
- Findings suggest a link between PRP clearance efficiency and the severity of Hib meningitis and subsequent immune response.
Abstract:
In systemic infections caused by Hemophilus influenzae, type b, the capsular polysaccharide, polyribophosphate, is released into the circulation. Polyribophosphate was quantitated in serial serum and cerebrospinal fluid samples from 45 children with H. influenzae, type b meningitis by means of a radiolabeled antigen-binding inhibition assay. Polyribophosphate was regularly found in acute serum and cerebrospinal fluid samples and could be detected in unbound form for periods of 1-30 days after initiation of effective therapy. Complexes of polyribophosphate dissociable with acid and pepsin were detected in serum samples from 17 patients, in one case for a period of 145 days after hospitalization. Polyribophosphate levels and patterns of clearance were studied in relation to hospital course and antibody response. Patients with prolonged antigenemia had protracted fevers and severe neurological symptoms during hospitalization, frequently with focal complications.Antipolyribophosphate antibody responses were detected during the first 100 days of convalescence by radioimmunoassay in 79% of the patients studied, including 60% of the children 1 yr or less in age. The intensity of antibody response although clearly related to the age of the patient, was more reliably predicted by the efficiency of antigen clearance. Antibody responses were uniformly of low magnitude in patients with prolonged antigenemia, irrespective of age. Paients who failed to develop antibody to polyribophosphate after meningitis also exhibited impaired antigen clearance. These studies suggest that mechanisms necessary for clearance of polyribophosphate may influence the development and intensity of the humoral immune response and raise the possibility of developmental deficiencies in the clearance system in infants and children.
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