Humoral immunity in DiGeorge syndrome.

OBJECTIVE

To assess humoral immunity after immunization and natural infection in patients with clinical manifestations of the DiGeorge anomalad.

DESIGN

Retrospective review of cases.

SETTING

Ambulatory immunology clinic of a tertiary care teaching hospital.

PATIENTS: The 13 patients had a symptom complex including congenital heart disease, characteristic facies of the DiGeorge anomalad, possible hypocalcemia, and thymic hypoplasia or aplasia. Molecular and cytogenic studies of 12 patients demonstrated that all had 22q11 microdeletions.

METHODS

Serial studies included lymphocyte population enumeration by flow cytometry, lymphocyte proliferation assays with the mitogens phytohemagglutinin and pokeweed mitogen and Staphylococcus aureus, and immunoglobulin quantitation. Specific antibody studies included virus neutralization assays for poliovirus antibodies, and enzyme-linked immunosorbent assay for diphtheria, tetanus, measles, rubella, varicella-zoster virus (VZV), and cytomegalovirus (CMV) antibodies. Avidity of rubella, VZV, and CMV antibodies was tested by enzyme-linked immunosorbent assay modified to include a mild protein denaturant in the first wash after incubation with sera.

RESULTS

All patients had a CD3+ cell count greater than 0.500 x 10(9)/L and a CD4+ cell count greater than 0.350 x 10(9)/L). One patient had low proliferation responses to S. aureus, and one to phytohemagglutinin and pokeweed mitogen. Immunoglobulin levels, compared with those in age-related control subjects, were normal except that two patients had transient, borderline low IgG levels and two had elevated IgA levels. Specific antibody tests showed (No. of patients with positive results/No. tested) the following: diphtheria (13/13); tetanus (13/13); poliomyelitis caused by polio virus type 1 (5/9), type 2 (9/9), and type 3 (8/9); measles (11/13); rubella (11/13); and infection with VZV (5/5) and CMV (7/13). There were no significant differences in antibody avidity results between patients and control subjects for rubella (mean avidity index, 83.5 +/- 8.79 vs 85 +/- 17.6), VZV (81.6 +/- 3.98 vs 65.1 +/- 12.38), or CMV (69.3 +/- 22.31 vs 73.3 +/- 12.46).

CONCLUSIONS

Patients with "partial" DiGeorge anomalad, defined by clinical and immunologic criteria, can be immunized and for the most part can generate good antibody responses.