Immunological features of Down's syndrome: a review

ABSTRACT Young patients with Down's syndrome (DS) have high rates of infections, malignancies and autoimmune phenomena. Therefore, DS may be considered as a model of precocious, abnormal ageing of the thymus‐dependent system in man. In DS children less than 6 years of age, the levels of serum immunoglobulins did not differ from healthy controls, but after that age, considerable hyper‐IgG and ‐IgA were found. Furthermore, high levels of IgGl and IgG3 have been found, whereas a progressive decline of IgG2 and IgG4 with age has been observed. The frequency of hepatitis B virus carriers even in the youngest age group is much higher among DS children. It has been reported that an IgG response was detectable in 75% of controls after HBsAg vaccination as compared to the 16–6% of DS patients. The presence of autoantibodies against human thyroblobulin did show a positive association with HB Virus Ag carriers, but only in the oldest DS subjects. Natural antibodies against intestinal antigens 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 normal percentage of CD3‐ and CD2‐positive lymphocytes, a high proportion of cells express low‐avidity receptors for sheep erythrocytes. Although the proportion of CD4+ T‐lymphocyte helper‐cells is normal, a marked imbalance in the CD4+ subpopulations has been documented. The percentage of suppressor‐cytotoxic CD8+ lymphocytes is markedly increased. The responses to phytoemagglutinin and concanavalin A are within the normal range in the first decade of life and decline progressively thereafrer. A recent study reported defective proliferative response to allo‐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+ cells was considerably lower for DS subjects than for controls, while DS subjects had a markedly higher proportion of cells expressing TCR gamma and delta. Therefore, it can be concluded that, while the primary immune 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.