thymic-factor--circulating and Down-Syndrome

Plasma levels of TSH, T4, T3, and reversal T3 (rT3) were measured in 51 children with trisomy of the chromosome 21 and in 15 controls. Levels of TSH were higher in children with DS than in controls and rT3 levels were decreased. However, T3 and T4 levels were in the normal range. Plasmic zinc and thymulin, a zinc-dependent thymic hormone, were also decreased. After dietary supplementation with ZnSO4, levels of plasmic zinc, thymulin, TSH and rT3 were restored. A follow up of DS children one year after the cessation of zinc therapy showed that plasma levels of zinc decreased and TSH lightly increased. Zinc deficiency may play a crucial role in the pathogenesis of thyroid gland disfunction which leads to the autoimmune hypothyroidism often observed in this syndrome.

Topics: Down Syndrome; Female; Follow-Up Studies; Humans; Male; Sulfates; Thymic Factor, Circulating; Thyroid Hormones; Thyrotropin; Thyroxine; Triiodothyronine; Triiodothyronine, Reverse; Zinc; Zinc Compounds; Zinc Sulfate

Retrospective analysis of five Down's syndrome (DS) patients who presented with recurrent infection revealed that all had initial low thymulin levels. Three patients had low cellular zinc levels that normalized after zinc replacement. Contrary to previous studies, thymulin levels were persistently low in four of five DS patients despite maintaining or achieving normal cellular zinc levels. A primary thymic epithelial defect may be responsible for the persistent thymulin deficiency in DS patients.

Topics: Adult; Child; Child, Preschool; Down Syndrome; Female; Humans; Male; Retrospective Studies; Thymic Factor, Circulating; Zinc

The effect of 4 months of oral zinc supplementation on immune functions in non-institutionalized young female and male Down's syndrome (DS) subjects was studied. Along with plasma levels of zinc, the immune parameters, measured before and after zinc treatment, were plasma levels of thymulin, the percentage and the absolute number of circulating white blood cells, total lymphocytes, lymphocyte subpopulations, the mitogen-induced lymphocyte proliferation, the production of interleukin-2, and the activity of stimulated granulocytes. Some immune parameters were significantly influenced by zinc treatment. In particular, a normalization of thymulin and zinc plasma levels were found in these subjects after zinc supplementation. At the end of the clinical trial, in vitro lymphocyte proliferation and polymorphonuclear activity also increased and reached normal values. Zinc administration exerted a positive clinical effect in these children, since a reduced incidence of infections was found.

Topics: Administration, Oral; Adolescent; Child; Down Syndrome; Female; Humans; Immunity, Cellular; Incidence; Infection Control; Interleukin-2; Leukocytes; Lymphocytes; Male; Respiratory Tract Infections; Sex Factors; Thymic Factor, Circulating; Zinc

Eighteen non-institutionalized Down's syndrome (DS) children (mean age: 7.0 +/- 10/12 years) with a history of respiratory tract, auditory and skin infections, low plasma levels of a nonapeptide thymic hormone, i.e. Serum Thymic Factor (STF), high plasma levels of inactive zinc-unbound STF molecules, and reduced absolute number of circulating T-lymphocytes, were given an oral non-pharmacological supplementation of zinc sulphate (1 mg Zn++/kg body weight/day for 2 months; two cycles, 10 months apart) and monitored immunologically before and after each cycle. A dramatic increase of plasma STF level and concomitantly an almost complete disappearance of inactive STF molecules was observed after each cycle. The absolute number of circulating T-lymphocytes was significantly increased by zinc treatment. The marginal zinc deficiency was also corrected without any appreciable influence on copper plasma levels. A reduction of recurrent infections and an improvement in school attendance after zinc supplementation were recorded. These beneficial effects of zinc supplementation were also noted in those DS children who did not show an apparent zinc deficiency, as assessed by measuring zinc plasma level. The reduced number of circulating B lymphocytes and the impaired lymphocyte responsiveness to phytohaemagglutinin and concanavalin A were not restored. On the whole, these findings suggest that there exists a defect in the bio-availability and/or in the utilization of zinc in DS. This alteration, of unknown origin, can be underestimated on the simple basis of the zinc plasma level and can be corrected with moderate nutritional zinc supplementation.

Topics: Child; Copper; Down Syndrome; Female; Humans; Immunologic Deficiency Syndromes; Leukocyte Count; Male; Opportunistic Infections; Sulfates; Thymic Factor, Circulating; Thymus Hormones; Zinc; Zinc Sulfate

Normal individuals aged over 50 and most young Down's syndrome (DS) subjects had markedly reduced concentrations of circulating thymic hormone (facteur thymique sérique, FTS). Plasma from these two groups contained factors capable of inhibiting biological activity of FTS in vitro. Addition of zinc sulphate to plasma samples from DS subjects or the older individuals induced concentrations of FTS comparable to those observed in young healthy people and completely prevented FTS-inhibitory activity. These findings suggest that biologically active circulating thymic hormone is bound to zinc. The decline in thymic hormone activity in older individuals and DS subjects may be the result of changes in the mechanism of zinc-dependent activation of FTS molecules, which are probably associated with marginal zinc deficiency rather than with a primary failure of the thymus. Addition of zinc salt to plasma samples unmasks the presence of inactive FTS molecules.

Topics: Adolescent; Adult; Aged; Aging; Child; Child, Preschool; Down Syndrome; Humans; Immunologic Deficiency Syndromes; Infant; Infant, Newborn; Middle Aged; Molecular Weight; Sulfates; T-Lymphocytes; Thymic Factor, Circulating; Thymus Gland; Thymus Hormones; Zinc; Zinc Sulfate

The immune competence of the T lymphocyte system was studied in 28 noninstitutionalized subjects with Down's syndrome (DS) and were compared with sex- and age-matched healthy controls. The ability of enriched T lymphocytes to respond to 3 different T cell stimulants revealed a selective impairment of T lymphocyte subset(s). Subjects with DS showed normal responsiveness in allogeneic mixed lymphocyte reactions, but their response to phytohemagglutinin and in autologous mixed lymphocyte reactions was severely impaired. Non-T cells from DS subjects stimulated equally well both normal and DS allogeneic T lymphocytes. The blood concentration of serum thymic factor in the majority of DS subjects was much lower than that found in age-matched healthy controls. These data support the hypothesis that a deficiency of the T-dependent regulatory system is an intrinsic feature of DS and confirm the precocious aging of the immune system in these subjects.

Topics: Adolescent; Adult; Aging; Child; Down Syndrome; Female; Humans; Immunologic Deficiency Syndromes; Lymphocyte Culture Test, Mixed; Male; Phytohemagglutinins; T-Lymphocytes; Thymic Factor, Circulating; Thymidine; Thymus Hormones

The activity of thymus-dependent serum factor SF was significantly lower in 18 children wit Down's syndrome (DS) than in 14 matched controls. The percentage of circulating T lymphocytes forming E-rosettes was also low in DS. Together with the previous finding of immature of T lymphocytes in peripheral blood, the present data suggest that the basic immune defect of DS is failure in differentiation of peripheral post-thymic precursors to fully immunocompetent T lymphocytes resulting from lack of thymic hormonal factors.

Topics: Child, Preschool; Down Syndrome; Humans; Immunologic Deficiency Syndromes; Infant; Rosette Formation; Thymic Factor, Circulating; Thymus Hormones; Trisomy