Antibody response to bordetella pertussis infection / Gunilla Zackrisson.

Tese (doutor) - University of Göteborg, 1989

The aims of this project were to develop an ELISA for determination of antibodies to pertussis toxin (PT), to evaluate antibody determinations against PT and filamentous hemagglutinin (FHA) with ELISA for diagnosis of pertussis, to study the IgG subclass composition of PT antibodies after natural disease and vaccination, to relate presence or absence of antibo-dies to PT and FHA to a history of clinical pertussis in non-vaccinated children, and to study IgA antibodies in saliva in patients with pertussis. ELISA for determination of serum antibodies to PT using fetuin for pre-coating resulted in improved specificity, high reproducibility and sensitivity. Significant antibody responses to PT of IgG, IgM and/or IgA classes were observed in 83% (143/172) of patients with clinical pertussis, while 80% (126/158) responded against FHA in at least one antibody class. When the serological results for PT and FHA were combined, 93% of patients with symptoms of whooping cough could be diagnosed as having pertussis. Culture alone was positive in 58%. A combination of both culture and serology resulted in a laboratory diagnosis in 97% of patients with clinical pertussis. The IgG antibodies to PT were mainly of the IgG1 subclass and to a certain extent IgG3 in patients with pertussis. IgG1 was also predominant in healthy individuals. In children vaccinated with a detoxified PT, the main subclass in addition to IgG 1 was IgG4. The prevalence of serum antibodies to PT and FHA in 266 non-vaccinated children aged 0-4 years increased with age. Of the 4-year-old children, 74% had antibodies to one or both antigens. There was a good correlation between the presence of antibodies to PT and FHA and a history of whooping cough. However, subclinical or atypical infections, resulting in an anti-body response to PT and FHA, appear to be fairly common. Follow-up 2-4 years later indicated that PT antibodies but not FHA antibodies alone may be protective against pertussis. ELISA was more sensitive than a neutralisation test for detecting low levels of antibodies to PT in the healthy children. IgA antibodies to FHA and PT in saliva developed in the majority of patients with pertussis. All samples obtained within 5 days of onset of symptoms lacked detectable antibodies to both FHA and PT. Of the samples obtained 6 to 49 days after onset of symptoms, 72% had detectable FHA antibodies while only 40% had measurable PT antibodies. Only about one -third of the patients had 4-fold increases in IgA antibodies to FHA and about one fourth in IgA antibodies to PT in saliva in paired samples. The majority of healthy adults had measurable IgA antibodies to FHA in saliva, several with high titres. Thus, determination of saliva antibodies is of less diagnostic value than determination of serum antibodies against the two antigens.