Increased spontaneous, tumor necrosis factor receptor- and CD95 (Fas)-mediated apoptosis in cord blood T-cell subsets from Turner's syndrome

Abstract

Increased spontaneous as well as TNF-a-induced and CD95-mediated apoptosis were observed in CD4+ and CD8+ T cells from the cord blood of a patient with Turner's syndrome as compared to normal cord blood. Increased apoptosis was associated with an increased expression of TNFR-1, TNFR-2, and CD95L and decreased expression of cIAP1 and FLIP L . No significant difference was observed in the expression of Bcl-2 family members (Bcl-2, Bax) between Turner's syndrome cord blood and normal cord blood lymphocytes. This study demonstrates that increased apoptosis of T-cell subsets in Turner's syndrome occurs via the death receptor pathway and may play a role in the pathogenesis of immunological defects associated with Turner's syndrome.

Epidemiological, endocrine and metabolic features in Turner syndrome

“…The basis for the grossly increased risk of autoimmunity in Turner syndrome (also including celiac disease (280), and diabetes (see above)) is unaccounted for, and a genetic basis seems probable. A recent study shows increased tumor necrosis factor receptor-and CD95-mediated apoptosis in cord blood T-cells (CD4 þ and CD8 þ cells) (281), and earlier studies found minor deficiencies of humoral and cellular immunity (114, 245, 282 -286), and it may be that these more or less discrete deficiencies in combination explain the increased risk of autoimmunity. GH treatment does not increase the frequency of auto-antibodies, although the percentage of antithyroid auto-antibodies did increase during treatment; however, no control group was included, and the number of patients with antithyroid antibodies does increase with age (287).…”

Heterogeneous loss of the Y chromosome in leukocyte lineages of donor origin after stem cell transplantation

“…[5][6][7] Moreover, monosomy X in T cells would be related to an increased spontaneous as well as death receptor-meditated apoptosis. 8 In addition, monosomy X T cells and monocytes of these patients showed a decreased sensitivity to insulin-like growth factor I (IGF-1) and growth hormone, and therefore a decreased monocyte-stimulated T lymphocyte proliferation. 9 On the other hand, studies aimed to identify specific genes responsible for the Turner syndrome phenotype suggest that many characteristic features are caused by haploinsufficiency of specific genes for which a diploid dosage would be required for their normal function.…”

Allogeneic stem cell transplantation from donors with mosaic Turner syndrome

“…Loss of specific genes located on the Xchromosome are thought to be responsible for a range of disorders, including osteoporosis, hypothyroidism, diabetes mellitus (DM), cardiovascular and gastrointestinal diseases, ophthalmic disorders, as well as various immunological defects. 1,2 We report two cases of allogeneic stem cell transplantation (SCT) in which 45,X/46,XX stem cells derived from donors with mosaic TS were used.…”

“…3 Various immunological disturbances have been detected in patients with TS, including decreased numbers of circulating T-lymphocytes. 2,4 Consequently, the study of immune recovery of the donor's 45,X T cells following SCT is particularly interesting, because it might influence infectious complications, antitumor activity, the development and the extent of acute and chronic GVHD, as well as the process of engraftment of hematopoietic stem cells. It is also not clear if 45,X hematopoietic stem cells would respond normally to immunosuppression.…”

“…To investigate the origin of 45,X cells, the donor's constitutional karyotype was evaluated, confirming a mosaic TS 45,X[15]/46,XX [5]. The disease relapsed at 9 months and cytogenetic analysis revealed 45,X [8]/46,X,t(X;22)(p11.3; q12),t(2;16)(p11;q11) [2]/46,XX [16]. A second allograft was performed from the same donor in second remission after total body irradiation-based conditioning and attenuated GVHD prophylaxis.…”