Immunological features of Down's syndrome: a review
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L Nespoli1, G R Burgio, A G Ugazio
1Department of Pediatrics, University of Pavia, Italy.
Insights
Down syndrome (DS) in children is linked to immune system abnormalities, suggesting premature immune aging. Research shows altered immunoglobulin levels and impaired responses to infections and vaccinations in DS patients.
Area of Science:
- Immunology
- Genetics
- Pediatrics
Background:
- Down syndrome (DS) is associated with increased susceptibility to infections, malignancies, and autoimmune disorders.
- DS may serve as a model for accelerated immune system aging, particularly the thymus-dependent system.
- Previous research indicates altered immune profiles in young DS patients.
Purpose of the Study:
- To investigate the specific immunological abnormalities in young patients with Down syndrome.
- To characterize the immunoglobulin profiles, antibody responses, and T-cell subset distributions in DS.
- To explore the relationship between immune dysfunction and increased disease risk in DS.
Main Methods:
- Serum immunoglobulin levels (IgG, IgA, IgG subclasses) were measured.
- Antibody responses to Hepatitis B virus (HBV) vaccination were assessed.
- T-lymphocyte populations (CD3, CD2, CD4, CD8) and their functions were analyzed.
- Autoantibodies and antibodies against dietary antigens were investigated.
Main Results:
- Elevated IgG and IgA levels were observed in DS children over 6 years old, with specific shifts in IgG subclasses (increased IgG1/IgG3, decreased IgG2/IgG4).
- DS patients showed significantly lower response rates to HBV vaccination compared to controls.
- Increased prevalence of Hepatitis B virus carriers and associations between autoantibodies and viral antigens were noted.
- Abnormal antibody responses to intestinal antigens (casein, beta-lactoglobulin, gliadin) were present.
- While T-cell percentages were largely normal, functional deficits were observed, including altered T-cell avidity, CD4+ subpopulation imbalance, increased CD8+ T-cells, and impaired proliferative responses to mitogens and alloantigens.
Conclusions:
- Young Down syndrome patients exhibit distinct immunological dysregulations, including altered immunoglobulin patterns and impaired adaptive immunity.
- These immune abnormalities contribute to the increased risk of infections, autoimmune phenomena, and potentially malignancies observed in DS.
- The findings support the concept of premature immune aging in Down syndrome, highlighting the need for targeted immune monitoring and support.
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 IgG1 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 thyroglobulin 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 beta-lactoglobulin 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 phytohemagglutinin and concanavalin A are within the normal range in the first decade of life and decline progressively thereafter. 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.(ABSTRACT TRUNCATED AT 250 WORDS)