Selective defect in the antibody response to type b in children with recurrent infections and normal serum IgG subclass levels

Ambrosino, Donna M.; Umetsu, Dale T.; Siber, George R.; Howie, G; Goularte, T A; Michaels, Richard H.; Martín, Paloma; Schur, Peter H.; Noyes, J; Schiffman, Gerald

doi:10.1016/0091-6749(88)90887-1

Cited by 85 publications

(29 citation statements)

References 26 publications

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“…Selective antipolysaccharide antibody deficiency is associated with a variable clinical spectrum of recurrent and/or severe respiratory tract infections [7,24]. Bronchiectasis develops because respiratory pathogens are not handled adequately due to this humoral immunodeficiency, which results in permanent damage of lung tissue.…”

Section: Discussionmentioning

confidence: 99%

Impaired pneumococcal antibody response in bronchiectasis of unknown aetiology

Kessel

Velzen‐Blad²,

Bosch³

et al. 2005

Eur Respir J

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As a defective anti-polysaccharide response can exist in the absence of an immunoglobulin deficiency, a series of 26 patients with bronchiectasis of unknown aetiology was vaccinated with a 23-valent pneumococcal polysaccharide vaccine. All patients suffered from recurrent respiratory tract infections.When measuring total antibody levels to pneumococcal serotypes 3, 4 and 9, a normal polysaccharide antibody response was found in 22 patients. However, only 11 of these subjects showed a normal pneumococcal antibody response within the IgA and/or IgG2 subclass, and thus could be classified as true responders, while 15 patients did not respond in either the IgA class or in the IgG2 subclass.When analysing differences between the responder (n511) and nonresponder (n515) groups, the latter demonstrated higher frequencies of respiratory tract infections and more severe lung pathology, as revealed by the presence of more bronchi visualised in the peripheral third of the lung by high-resolution computed tomography scanning. Moreover, nonresponders needed extensive lung surgery more often in order to control their disease (number of resected segments eight versus five).In conclusion, an important fraction of patients presenting with idiopathic bronchiectasis is associated with a selective anti-polysaccharide response deficiency and this subgroup appears to represent a more severe clinical phenotype. Therefore, it can be regarded as a separate clinical entity with possible therapeutic targets.In order to identify IgA and IgG2 anti-polysaccharide nonresponders, all patients presenting with bronchiectasis of unkown aetiology should be immunised with a pneumococcal polysaccharide vaccine, and IgA and IgG2 isotype responses should be evaluated as well as the total antibody response.

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Section: Discussionmentioning

confidence: 99%

Impaired pneumococcal antibody response in bronchiectasis of unknown aetiology

Kessel

Velzen‐Blad²,

Bosch³

et al. 2005

Eur Respir J

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“…The first description of such a patient was published in 1987 (3). A considerable number of other reports followed (4,15,21,29). Therefore, several vaccines are being developed based on the expectation that the immunogenicity of the polysaccharide antigens is improved by linking them to a protein carrier (conjugate vaccine) (24).…”

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confidence: 99%

Immunogenicity and Tolerance of a 7-Valent Pneumococcal Conjugate Vaccine in Nonresponders to the 23-Valent Pneumococcal Vaccine

et al. 2000

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There is still a lack of effective vaccination strategies for patients with a deficient antibody response to bacterial polysaccharide antigens. In an open trial, we evaluated the immunogenicity and tolerance of a new 7-valent pneumococcal conjugate vaccine in 22 infection-prone nonresponders to pneumococcal polysaccharide vaccine and 21 controls. In the patient group, nonresponsiveness was confirmed by repeated vaccination with a 23-valent pneumococcal polysaccharide vaccine. The study protocol provided two doses of the pneumococcal conjugate vaccine, given 4 to 6 weeks apart, for both groups. The antibody response was determined before each vaccination and on follow-up by an enzyme-linked immunosorbent assay and compared to the response in a functional opsonophagocytosis assay. Patients showed a significantly lower postvaccination immune response for all serotypes than did controls. The postvaccination response was serotype dependent. A median titer of >1 g/ml in patients was recorded only for serotypes 4, 9V, 14, and 19F, which are known to be more immunogenic than serotypes 6B, 18C, and 23F. In the patient group, 70% responded to serotype 19F (Pnc 19F), 65% responded to Pnc 14 and 4, 60% responded to Pnc 9V, 55% responded to Pnc 18C, 50% responded to Pnc 23F, and 25% responded to Pnc 6B. In the control group >95% of individuals showed a titer of >1 g/ml to every serotype. The vaccine was tolerated well, and no major side effects have been reported. The new pneumococcal conjugate vaccine is clearly more immunogenic in previous nonresponders than is the 23-valent pneumococcal vaccine. Immunization with a pneumococcal conjugate vaccine should be considered as a strategy to protect high-risk patients.

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“…Interpretation of the results may be difficult. Although patients with congenital immunodeficiencies, such as common variable immunodeficiency (1, 7), selective immunoglobulin G (IgG) subclass deficiency (2,8), and selective antibody deficiency with normal immunoglobulins (2), often have low levels of serum antibodies, many subjects with normal immune function also have low levels of serum-specific antibodies. A physiological delay of the immune response, especially to polysaccharide capsular antigens, a lack of immunization and, in addition, a decrease in specific antibody titers with time (11,18) determine the outcome of serumspecific antibody measurements.…”

mentioning

confidence: 99%

Levels of Antibodies Specific to Tetanus Toxoid,Haemophilus influenzaeType b, and Pneumococcal Capsular Polysaccharide in Healthy Children and Adults

Schauer

Stemberg

Rieger

et al. 2003

Clin Vaccine Immunol

114

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Antibody levels specific for capsular polysaccharides of Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) and for tetanus toxoid were measured in serum samples of 386 age-stratified subjects. The study group consists of healthy adult blood donors and hospitalized children undergoing elective surgery, excluding individuals with a history of infection. In children, anti-tetanus toxoid antibody levels displayed two peaks of 1.20 IU/ml (20.4 mg/liter) and 1.65 IU/ml (28.1 mg/liter) related to the schedule of routine childhood immunization in the first year and at 8 years of age. Eighty percent of the antibodies are of the immunoglobulin G1 (IgG1) isotype. For pneumococcal capsular polysaccharide (PCP), the specific antibody levels represent the acquisition of natural immunity. The initial concentration of 9.2 mg/liter was low in infancy (0.5 to 1 years of age) and remained low until 3 to 4 years of age (14.6 mg/liter). During this period PCP antibodies were almost 100% of the IgG2 subclass. Thereafter, IgG anti-PCP antibody titers increased steadily to adult levels (59.5 mg/liter). The data are intended to provide reference ranges to aid in the interpretation of specific antibody determinations in the clinical setting.Serum-specific antibody levels are widely used as indicators of immune competence (25,31). Interpretation of the results may be difficult. Although patients with congenital immunodeficiencies, such as common variable immunodeficiency (1, 7), selective immunoglobulin G (IgG) subclass deficiency (2, 8), and selective antibody deficiency with normal immunoglobulins (2), often have low levels of serum antibodies, many subjects with normal immune function also have low levels of serum-specific antibodies. A physiological delay of the immune response, especially to polysaccharide capsular antigens, a lack of immunization and, in addition, a decrease in specific antibody titers with time (11, 18) determine the outcome of serumspecific antibody measurements. Furthermore, in recent years the routine vaccination schedule has changed. In particular, Haemophilus influenzae type b (Hib) conjugate was introduced (36). Moreover, routine enzyme-linked immunosorbent assay (ELISA) test kits became available that allow specific antibodies to be assigned to IgG subclasses. The present study was designed to establish the pattern of specific antibody responses to polysaccharide and protein antigens in a large cohort of healthy subjects from Germany. MATERIALS AND METHODSSubjects. The subjects of the present study were 313 clinically healthy children (214 males and 99 females) from 6 months to 18 years of age who were admitted to the hospital for minor surgery. Informed consent was obtained from the parents. The adult subjects were 73 healthy blood donors (36 males and 37 females) ranging from 20 to 61 years of age. Only subjects who were free of recurrent infections or inflammation, as assessed by a standardized questionnaire, and whose C-reactive protein concentrations were within the normal limit were incl...

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Selective defect in the antibody response to type b in children with recurrent infections and normal serum IgG subclass levels

Cited by 85 publications

References 26 publications

Impaired pneumococcal antibody response in bronchiectasis of unknown aetiology

Impaired pneumococcal antibody response in bronchiectasis of unknown aetiology

Immunogenicity and Tolerance of a 7-Valent Pneumococcal Conjugate Vaccine in Nonresponders to the 23-Valent Pneumococcal Vaccine

Levels of Antibodies Specific to Tetanus Toxoid,Haemophilus influenzaeType b, and Pneumococcal Capsular Polysaccharide in Healthy Children and Adults

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