Thymus transplantation for complete DiGeorge syndrome: European experience.

BACKGROUND: Thymus transplantation is a promising strategy for the treatment of athymic complete DiGeorge syndrome (cDGS). METHODS: Twelve patients with cDGS underwent transplantation with allogeneic cultured thymus. OBJECTIVE: We sought to confirm and extend the results previously obtained in a single center. RESULTS: Two patients died of pre-existing viral infections without having thymopoiesis, and 1 late death occurred from autoimmune thrombocytopenia. One infant had septic shock shortly after transplantation, resulting in graft loss and the need for a second transplant. Evidence of thymopoiesis developed from 5 to 6 months after transplantation in 10 patients. Median circulating naive CD4 counts were 44 × 106/L (range, 11-440 × 106/L) and 200 × 106/L (range, 5-310 × 106/L) at 12 and 24 months after transplantation and T-cell receptor excision circles were 2,238/106 T cells (range, 320-8,807/106 T cells) and 4,184/106 T cells (range, 1,582-24,596/106 T cells). Counts did not usually reach normal levels for age, but patients were able to clear pre-existing infections and those acquired later. At a median of 49 months (range, 22-80 months), 8 have ceased prophylactic antimicrobials, and 5 have ceased immunoglobulin replacement. Histologic confirmation of thymopoiesis was seen in 7 of 11 patients undergoing biopsy of transplanted tissue, including 5 showing full maturation through to the terminal stage of Hassall body formation. Autoimmune regulator expression was also demonstrated. Autoimmune complications were seen in 7 of 12 patients. In 2 patients early transient autoimmune hemolysis settled after treatment and did not recur. The other 5 experienced ongoing autoimmune problems, including thyroiditis (3), hemolysis (1), thrombocytopenia (4), and neutropenia (1). CONCLUSIONS: This study confirms the previous reports that thymus transplantation can reconstitute T cells in patients with cDGS but with frequent autoimmune complications in survivors.

Breast milk cytokine and IgA composition differ in Estonian and Swedish mothers-relationship to microbial pressure and infant allergy.

The immune system of the neonate is influenced by maternal immunity during pregnancy and lactation. An altered microbial exposure, possibly underlying the increase of allergic diseases in affluent societies, may affect maternal breast milk immune composition. Secretory IgA (SIgA), IL-4, IL-10, IL-13, IFN-[gamma], TGF-[beta]1, and TGF-[beta]2 were analyzed with ELISA in colostrum and 1-mo mature milk from mothers from Estonia (n = 39) and Sweden (n = 60), the two geographically adjacent countries with different living conditions and allergy incidence. The IL-10 and IFN-[gamma] levels were higher in colostrum from Estonian than Swedish mothers, whereas the opposite was true for TGF-[beta]2. In mature milk, higher SIgA and IFN-[gamma] levels but lower TGF-[beta]1 and TGF-[beta]2 levels were observed in Estonian than Swedish mothers. Interestingly, in Sweden but not Estonia, the TGF-[beta]1 and TGF-[beta]2 levels correlated inversely with environmental endotoxin concentrations, whereas positive correlations to microbial load were observed for IL-4, IL-10, and IFN-[gamma]. High colostral IL-13 levels were associated with allergic sensitization during infancy in Sweden. In conclusion, Estonian mothers have lower breast milk levels of TGF-[beta], particularly TGF-[beta]2, but higher levels of SIgA, IL-10, and IFN-[gamma] than Swedish mothers, possibly because of differences in microbial load.