Development of specific T-cell responses to Candida and tetanus antigens in partial DiGeorge syndrome

Background

Partial DiGeorge syndrome (pDGS) presents with thymic hypoplasia and a variable decrease in T-cell numbers. Although lymphocyte proliferation to mitogens is generally preserved, it is uncertain whether the development of specific cellular immunity in pDGS is similarly preserved.

Objective

We sought to study the development of antigen-specific T-cell responses in patients with pDGS with regard to their initial CD3 T-cell counts.

Methods

A retrospective review of 93 patients with pDGS followed at Texas Children's Hospital Allergy and Immunology Clinic from 1991 to 2006 was performed. Serial lymphocyte proliferation to Candida and tetanus antigens was longitudinally analyzed. Antigen-specific lymphoproliferation was compared with initial patient CD3 T-cell counts of less than the 10th percentile (n = 63), the 10th to 50th percentile (n = 20), and greater than the 50th percentile (n = 10) of age-matched normal control values. Tetanus-specific IgG levels and the number of tetanus immunizations were also studied.

Results

The median CD3 T-cell counts at baseline in all 3 groups were as follows: 10th percentile, 1188 cells/mm³ (range, 168-3272 cells/mm³); 10th to 50th percentile, 2816 cells/mm³ (range, 1484-4155 cells/mm³); greater than 50th percentile, 4246 cells/mm³ (range, 2573-6481 cells/mm³). Thirty-one (46%) of 68 patients with pDGS who received at least 3 tetanus vaccines had persistent Candida and tetanus-specific cellular immunity, and 24 (35%) did not have immunity to either antigen. Most (22/24) of these patients had CD3 T-cell counts at presentation of less than the 10th percentile of normal values. Protective tetanus-specific IgG titers (>0.10 IU/mL) were detected in all patients tested from the age of 2 to 85 months (n = 72).

Conclusion

Some patients with pDGS with low CD3 T-cell counts might not have specific Candida and tetanus cellular immunity.

Key words: Partial DiGeorge syndrome, 22q11 deletion, velocardiofacial syndrome, T-cell deficiency, tetanus immunity, Candida species immunity

Abbreviations used: ConA, Concanavalin A, cpm, Counts per minute, DGS, DiGeorge syndrome, DTaP, Diphtheria, tetanus, and pertussis, LPA, Lymphocyte proliferation assay, pDGS, Partial DiGeorge syndrome, PHA, Phytohemagglutinin