The immune deficiency of the 22q11.2 deletion syndrome (formerly called DiGeorge or velocardiofacial syndrome (DS)), is due to impaired development of the thymus gland; therefore, the majority of the studies have focused on T cell numbers and function. Furthermore, a subgroup of patients with partial (p)DS appears to be at higher risk for relevant infectious and autoimmune complications. The number and function of dendritic cells (DCs) in the 22q11.2 DS has not been investigated, although these cells represent the most important family of professional antigen-presenting cells, able to efficiently prime naïve, memory and effector T cells and are responsible for activating also natural killer T (NKT) cells. Therefore, we have enumerated circulating DCs in 13 patients with partial 22q11.2 DS, directly from whole blood using a four-colours flow cytometric method. DCs are also examined for the expression of CD85k antigen because it is down-regulated following DC activation and up-regulated in tolerogenic DCs, leading to the induction of T reg cells. We report a significant decrease in the absolute number of total DCs compared to age-matched healthy controls, which affects both myeloid and plasmacytoid DC (mDC and pDC) subsets. In particular, 9 out of 13 patients have a total DC number under -1SD of control mean. Interestingly, the patient with the lowest mDC value suffered from metastatic thyroid cancer. The mean fluorescence intensity (MFI) of CD85k on mDCs is significantly higher in patients compared to controls, reaching in 7 patients values higher than +2SD of the mean of the controls. We suggest that the reduction of DCs could contribute to the immunodeficiency of this syndrome; additional investigations are necessary to dissect the heterogeneity observed in this population in order to early detect the subgroup of patients at higher risk of infections, tumours and/or autoimmune disorders.

Numerical alterations of dendritic cell subsets in the peripheral circulation of patients with partial 22q11.2 deletion syndrome

LEGITIMO, ANNALISA;CONSOLINI, RITA
2013

Abstract

The immune deficiency of the 22q11.2 deletion syndrome (formerly called DiGeorge or velocardiofacial syndrome (DS)), is due to impaired development of the thymus gland; therefore, the majority of the studies have focused on T cell numbers and function. Furthermore, a subgroup of patients with partial (p)DS appears to be at higher risk for relevant infectious and autoimmune complications. The number and function of dendritic cells (DCs) in the 22q11.2 DS has not been investigated, although these cells represent the most important family of professional antigen-presenting cells, able to efficiently prime naïve, memory and effector T cells and are responsible for activating also natural killer T (NKT) cells. Therefore, we have enumerated circulating DCs in 13 patients with partial 22q11.2 DS, directly from whole blood using a four-colours flow cytometric method. DCs are also examined for the expression of CD85k antigen because it is down-regulated following DC activation and up-regulated in tolerogenic DCs, leading to the induction of T reg cells. We report a significant decrease in the absolute number of total DCs compared to age-matched healthy controls, which affects both myeloid and plasmacytoid DC (mDC and pDC) subsets. In particular, 9 out of 13 patients have a total DC number under -1SD of control mean. Interestingly, the patient with the lowest mDC value suffered from metastatic thyroid cancer. The mean fluorescence intensity (MFI) of CD85k on mDCs is significantly higher in patients compared to controls, reaching in 7 patients values higher than +2SD of the mean of the controls. We suggest that the reduction of DCs could contribute to the immunodeficiency of this syndrome; additional investigations are necessary to dissect the heterogeneity observed in this population in order to early detect the subgroup of patients at higher risk of infections, tumours and/or autoimmune disorders.
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11568/522867
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