Distribution of primary immunodeficiency diseases diagnosed in a pediatric tertiary hospital.

BACKGROUND: Advances in immunologic techniques in recent years have led to increased recognition of primary immunodeficiency disorders, with IgA deficiency the most common phenotype reported by most registries. There have also been reports of increased associated incidence of autoimmunity, allergy, and other diseases. OBJECTIVES: We wished to determine the percentage of different primary immunodeficiency disorders seen in a pediatric tertiary hospital and to determine the association of primary immunodeficiency disorders with other diseases that are not part of classic immunodeficiency disorders. METHODS: We performed a retrospective review of the patients referred to our allergy/immunology clinic for immunologic evaluation of recurrent infections during an 8-year period. We also reviewed pathology reports with postmortem diagnosis of immunodeficiencies not identified while patients were alive. RESULTS: Of the 91 patients with primary immunodeficiency disorders evaluated, the majority had predominantly antibody deficiencies (67%). The most common phenotype was specific antibody deficiency with normal immunoglobulins (23.1%), defined as inability to mount an adequate response to pneumococcal polysaccharides followed by IgG2 subclass deficiency (17.6%). These two phenotypes were diagnosed mostly in the last 2 years of the survey. Associated diseases, found in 40% of patients, were mostly allergic conditions followed by syndromic/chromosomal disorders. CONCLUSION: The study reveals that specific antibody deficiency with normal immunoglobulins followed by IgG2 subclass deficiency was the most frequently diagnosed primary immunodeficiency disorder in our patient population. It also indicates that immunodeficiency disorders should be considered in patients with other abnormalities like allergic and syndromic/chromosomal disorders that present with recurrent infections.

Lead screening among low-income children in Galveston, Texas.

The objective of this study was to report results of a lead-screening program for low-income children living in Galveston, Texas. We obtained blood lead by graphite furnace spectrophotometry on 1,571 children aged 6 months to 8 years. Nineteen percent of children had blood lead levels > or = 10 mcg/dL. Risk factors included African-American ethnicity, young age, and residence in old housing. Follow-up was accomplished in only 50% of children with low-level toxicity. Lead screening is an important public health measure in communities with old houses. For screening to be successful, caregivers need to devote additional effort to follow-up.

Response to a heptavalent conjugate Streptococcus pneumoniae vaccine in children with recurrent infections who are unresponsive to the polysaccharide vaccine.

OBJECTIVE: To determine whether children with recurrent respiratory infections who failed to respond to the conventional polysaccharide vaccine would respond to a pneumococcal conjugate vaccine. METHODS: Children referred to our clinic for recurrent respiratory infections who had no known primary or secondary immunodeficiencies were immunized with a 23-valent pneumococcal polysaccharide vaccine. IgG antibodies to pneumococcal serotypes 1, 3, 4, 6B, 9V, 14, 18C, 19F and 23F were determined by enzyme-linked immunosorbent assay before and 4 to 6 weeks after immunization. An adequate IgG antibody response to an individual serotype was arbitrarily defined as a postimmunization antibody titer > or =1.3 microg/ml or at least 4 times the preimmunization value. Immunization with an experimental CRM197-heptavalent pneumococcal conjugate vaccine was offered to patients without an adequate response to 4 or more vaccine serotypes (nonresponders). Post-conjugate immunization antibody concentrations were measured 4 to 6 weeks later. RESULTS: In nonresponder patients (n = 17) geometric mean post-conjugate immunization (C) serum antibody concentrations (microg/ml) compared with post-polysaccharide (PS) concentrations were: (serotype, C vs. PS) 4, 1.11 vs. 0.30 (P = 0.000227); 6B, 0.46 vs. 0.20 (P = 0.017267); 9V, 0.82 vs. 0.29 (P = 0.002163); 14, 1.88 vs. 0.27 (P = 0.000615); 18C, 0.98 vs. 0.32 (P = 0.021962); 19F, 1.24 vs. 0.34 (P = 0.002844); and 23F, 0.87 vs. 0.16 (P = 0.000194). In responder patients (n = 67), after 1 dose of the polysaccharide vaccine, geometric mean antibody concentrations were: 4, 1.05; 6B, 0.96; 9V, 1.55; 14, 1.65; 18C, 1.62; 19F, 1.30; and 23F, 1.02. CONCLUSIONS: Our results show that a pneumococcal conjugate vaccine is capable of inducing an IgG response in patients with recurrent infections who had failed to mount an adequate response to the polysaccharide vaccine. Conjugate vaccines may be of value in the management of children with recurrent pneumococcal respiratory infections.

Influence of age on the response to Streptococcus pneumoniae vaccine in patients with recurrent infections and normal immunoglobulin concentrations.

BACKGROUND: A deficient antibody response to polysaccharide antigens is determined by measuring the response to the 23-valent pneumococcal polysaccharide vaccine. However, the diagnosis of this specific antibody deficiency is hampered by the lack of sufficient data and standardized testing of the response to pneumococcal polysaccharides. METHODS: All patients evaluated in our allergy/immunology clinic for recurrent respiratory infections between 1995 and 1997 without immunoglobulin, IgG subclass, or other known primary or secondary immunodeficiency were included in this analysis. IgG antipneumococcal serotypes 1, 3, 4, 6B, 9V, 14, 18C, 19F, and 23F were determined by a modified ELISA protocol. An adequate IgG antibody response to an individual serotype was arbitrarily defined as a postimmunization antibody titer of 1.3 microg/ml or greater or at least four times the baseline value. RESULTS: A total of 113 patients fulfilling the criteria for inclusion in this analysis were divided into five age groups. The geometric means for preimmunization and postimmunization pneumococcal antibody titers for all serotypes increased with age. For post-immunization antibody concentrations, there was a sharp increase in the specific antibody concentrations in adults in comparison with all pediatric age groups ranging in age from 7 months to 16 years. Similarly, the number of serotypes to which there was an adequate response also increased with age. CONCLUSION: We conclude that the definition of what constitutes an adequate response to pneumococcal immunization needs further definition. It is clear, however, that age has an important influence on the intensity of the response to most pneumococcal polysaccharides. Correlation studies between antibody concentrations in different IgG subclasses, functional studies, and protection studies against mucosal and invasive pneumococcal infections are in progress, and these should contribute to a refined definition of a normal response. The availability of a standardized method for the measurement of IgG antibodies against relevant pneumococcal serotypes is an important step toward this goal.