IMMUNOLOGICAL FEATURES OF DOWNS-SYNDROME - A REVIEW

Young patients with Down's syndrome (DS) have high rates of infections , malignancies and autoimmune phenomena. Therefore, DS may be consider ed as a model of precocious, abnormal ageing of the thymus-dependent s ystem in man. In DS children less than 6 years of age, the levels of s erum immunoglobulins did not differ from healthy controls, but after t hat age, considerable hyper-IgG and -IgA were found. Furthermore, high levels of IgG1 and IgG3 have been found, whereas a progressive declin e of IgG2 and IgG4 with age has been observed. The frequency of hepati tis B virus carriers even in the youngest age group is much higher amo ng DS children. It has been reported that an IgG response was detectab le in 75% of controls after HBsAg vaccination as compared to the 16.6% of DS patients. The presence of autoantibodies against human thyroblo bulin did show a positive association with HB Virus Ag carriers, but o nly in the oldest DS subjects. Natural antibodies against intestinal a ntigens are low, while in the presence of cow's milk, abnormally high titres against casein and betalactoglobulin were present. High levels of IgG antibodies against gliadin have been observed. In spite of a no rmal percentage of CD3- and CD2-positive lymphocytes, a high proportio n of cells express low-avidity receptors for sheep erythrocytes. Altho ugh the proportion of CD4+ T-lymphocyte helper-cells is normal, a mark ed imbalance in the CD4+ subpopulations has been documented. The perce ntage of suppressor-cytotoxic CD8+ lymphocytes is markedly increased. The responses to phytoemagglutinin and concanavalin A are within the n ormal range in the first decade of life and decline progressively ther eafter. A recent study reported defective proliferative response to al lo-mixed lymphocyte culture, with decreased expression of the membrane CD25, low secretion of interleukin 2 in the supernatant and depressed allo-specific cytotoxic activity. Defective production of interferon alfa and gamma in DS has been described in vivo and in vitro. Recently , it has been reported that the absolute number of TCR alfa, beta+ cel ls was considerably lower for DS subjects than for controls, while DS subjects had a markedly higher proportion of cells expressing TCR gamm a and delta. Therefore, it can be concluded that, while the primary im mune defect seems to be greatest in the cellular compartment, even the humoral immunity in DS subjects undergoes a precocious ageing, as has already been shown for the T-cell compartment.