Impaired polysaccharide responses in immunodeficient patients: relevance to bone marrow transplant patients

Abstract

Bone marrow transplant patients are at increased risk for pneumococcal and H. influenzae type b (HIB) infections. These polysaccharide encapsulated bacteria are also pathogens for young healthy children. In healthy children age related susceptibility has been associated with poor response to polysaccharides and low serum IgG2 subclass antibody concentrations. Of note, immune reconstitution following bone marrow transplantation has been characterized by slow return of both the response to polysaccharides and IgG2 serum concentrations. Thus immune reconstitution following bone marrow transplantation is similar to the maturation that occurs in healthy children. In addition to transplant patients, we have identified five groups of immunodeficient patients who are at increased risk for polysaccharide encapsulated pathogens. IgG2 subclass deficient patients were shown to have impaired responses to polysaccharide antigens. We have also defined "Selective Antibody Deficiencies" which are individuals with normal IgG subclass concentrations but poor responses to polysaccharide antigens. Next, patients who developed HIB disease in spite of immunization (i.e. HIB vaccine failures) were demonstrated to have lower serum IgG2 and IgG4 subclass concentrations compared to controls. Finally, Native Americans (an ethnic group with an increased incidence of pneumococcal and HIB infections) were shown to be poor responders to polysaccharide antigens and have significantly lower concentrations of serum IgG2 and IgG4 as compared to controls. New HIB polysaccharide vaccines linked to protein antigens (conjugate vaccines) have been developed that are more immunogenic in healthy young children. In addition, these conjugate vaccines have resulted in protective responses in each of the newly described immunodeficient groups. We therefore now propose to evaluate bone marrow transplant patients' response to HIB conjugate vaccine.(ABSTRACT TRUNCATED AT 250 WORDS)