PURPOSE OF THE STUDY.
To better characterize humoral immunity in patients with DiGeorge syndrome.
An international cohort of 1023 patients with DiGeorge syndrome was used in this investigation. This included data from 21 countries and 40 different contributors, including 662 records from the US Immunodeficiency Network, 381 from the European Society for Immunodeficiencies, 327 from the Children’s Hospital of Philadelphia, and fewer than 50 patients per institution from the remaining contributors.
The investigators defined a low serum immunoglobulin G (IgG) value as <500 mg/dL and a low CD3+ count as <500 cells/mm3 to stratify patients for the Pearson analysis. For patients with data from multiple points in time, data from the oldest age were used. Correlation coefficients were calculated using the Pearson method and linear regression analyses were performed within Prism. All P values were computed as 2-tailed.
The cohort consisted of 1023 patients with DiGeorge syndrome. The mean age was 5.5 years and median age was 3.0 years; 855 patients had immunoglobulin data available. Overall, 19% (150 total) of patients had IgG levels <500 mg/dL; 6.2% (28 total) of patients older than 3 and 5.6% (19 total) older than 5 years had levels of IgG <500 mg/dL. A total of 7 patients had undetectable IgA levels (IgA = 0 mg/dL); ages ranged from 4 to 15 years with the mean age of 8.7 years. A total of 10 patients (1.3%) had measurable IgA levels <5 mg/dL; all were older than 3 years. Twenty-seven percent of patients (216 total) had IgM levels <40 mg/dL; 23% (104 total) of patients older than 3 years had IgM levels <40 mg/dL.
The investigators found that 3% of patients with DiGeorge syndrome were receiving immunoglobulin replacement therapy and 6% of patients older than 3 years had hypogammaglobulinemia. The investigators concluded that DiGeorge syndrome, which is typically thought of as a T-lymphocyte disorder, was associated with significant humoral immune deficiency.
There has been a growing body of evidence that B-lymphocyte functional deficit and hypogammaglobulinemia are associated with more severe infections in DiGeorge syndrome. This investigation directly addresses this clinical issue and is the largest report to date of immunoglobulin levels in this patient population. The investigators clearly identified limitations of their registry approach to collect data. For example, the definition of DiGeorge syndrome was not uniform, the data sets were incomplete, and there may have been ascertainment bias in the overall analysis. Although imperfect, this registry approach was helpful in identifying an unexpectedly high frequency of humoral immune deficiency in patients with DiGeorge syndrome. A reasonable clinical strategy, as mentioned by the investigators, would be to measure IgG, IgA, and IgM levels and diphtheria and tetanus titers in immunized patients with DiGeorge syndrome with recurrent sinopulmonary infections. If humoral immunity is determined to be insufficient, additional beneficial therapies, such as immunoglobulin replacement therapy, should be considered.
- Copyright © 2013 by the American Academy of Pediatrics