Derangements of immunoglobulin levels, phytohemagglutinin responsiveness and T and B cell markers in Down's syndrome at different ages

Burgio, Giuseppe; Ugazio, Alberto G.; Nespoli, Luigi; Marcioni, A. F.; Bottelli, Antonella; Pasquali, Francesco

doi:10.1002/eji.1830050904

Cited by 120 publications

(77 citation statements)

References 18 publications

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“…It is still uncertain whether these cells function normally, having shown such a profound lack of the antigen-driven expansion in earlier years. In vitro tests of T lymphocyte function support this (30). No increased infection rate (all ages) n ϭ 5 n ϭ 6 n ϭ 5 n ϭ 1 n ϭ 2 n ϭ 19 Increased-mainly respiratory-infection rate (age at inclusion Ͻ8 y) n ϭ 6 n ϭ 4 n ϭ 10 n ϭ 20 n ϭ 40…”

Section: Discussionmentioning

confidence: 77%

Both Normal Memory Counts and Decreased Naive Cells Favor Intrinsic Defect Over Early Senescence of Down Syndrome T Lymphocytes

et al. 2010

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Because of their increased malignancies, autoimmune diseases, and infections, patients with Down syndrome (DS) show features of immunodeficiency. The DS thymus and T lymphocyte subsets have indeed proven to be different, and this has been interpreted as precocious aging. Our study on T lymphocyte subpopulations in DS shows that the normal expansion of naive helper (CD4 ϩ CD45RA ϩ ) and cytotoxic (CD8 ϩ CD45RA ϩ CD27 ϩ ) T lymphocytes is lacking in the first years of life; this is more logically explainable with an intrinsic T lymphocyte defect. Furthermore, memory cell numbers are not different from age-matched controls (AMC), which does not support the hypothesis of precocious aging. Although the absolute numbers of T lymphocyte subpopulations approach AMC levels toward adulthood, the persistent clinical problems suggest that these cells may not function optimally. However, the clinical picture does not fit severe T lymphocyte deficiency. The latter concept is also supported by our finding that cytomegalovirus (CMV)-seropositive DS children show similar numbers of terminally differentiated cytotoxic T lymphocytes when compared with healthy children, not increased numbers as are seen in immunocompromised hosts. (Pediatr Res 67: 557-562, 2010) D own syndrome (DS) is associated with a high frequency of hematological malignancies (1-4), autoimmune diseases like celiac disease and hypothyroidism (5-7), as well as recurrent, mainly respiratory, infections (2,8). This fits with immunodeficiency. Indeed, the thymus in DS children is smaller and abnormal (9 -13), and blood T lymphocyte subpopulations differ from healthy controls (14 -16). This has been interpreted as precocious aging of the immune system due to the lower relative number of CD4 ϩ CD45RA ϩ naive T lymphocytes (17,18) and lower T cell-receptor excision circle counts (19,20) in DS children. However, we recently showed (21) that the vast expansion of T lymphocytes in the first years of life is abrogated, favoring an intrinsic defect. We studied T lymphocyte subpopulations in DS children compared with age-matched controls (AMC) to analyze whether the results support this alternative theory. T lymphocyte differentiation and expansion are influenced by encountered viral infections. Especially, the expansion of CD45RA ϩ CD27 Ϫ terminally differentiated cytotoxic T lymphocytes (Tc), which is described as unique for cytomegalovirus (CMV) infection. The individual set point is defined by the degree of immunocompetence during the primary CMV contact: immunodeficient children show higher median absolute numbers of terminally differentiated Tc (22). To further assess the degree of immuno(in)competence in DS, we related T lymphocyte subpopulations to CMV serostatus and compared the DS children with groups from the literature with different immune status during primary CMV contact (22,23). METHODSStudy population. An extra 3 mL of EDTA blood and 7 mL of blood without additive was drawn from 95 noninstitutionalized DS children (49 males; mean age, 7 y; range, 1...

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Section: Discussionmentioning

confidence: 77%

Both Normal Memory Counts and Decreased Naive Cells Favor Intrinsic Defect Over Early Senescence of Down Syndrome T Lymphocytes

et al. 2010

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“…The latter has indeed been described (3,15). However, the T-cell-independent antibody response to pneumococcal polysaccharide antigen is also decreased in DS (4), suggesting an intrinsic B-lymphocyte defect is also present.…”

Section: Own Syndrome (Ds) Is Associated With Recurrent-mainlymentioning

confidence: 79%

“…Deficient T-lymphocyte help could lead to disturbed B-lymphocyte activation and proliferation. Despite the B lymphocytopenia, a considerable hypergammaglobulinemia of IgA and IgG after the age of 5 y, with high levels of IgG 1 and IgG 3 and low levels of IgG 2 and IgG 4 , is described (3,15,16).…”

Section: Own Syndrome (Ds) Is Associated With Recurrent-mainlymentioning

confidence: 99%

Down Syndrome B-Lymphocyte Subpopulations, Intrinsic Defect or Decreased T-Lymphocyte Help

et al. 2010

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Down syndrome (DS) is known for increased incidence of respiratory infections and autoimmune diseases, indicating impaired immunity. Until now, attention has been mainly focused on T lymphocytes. Therefore, we determined B-lymphocyte subpopulations in 95 children with DS compared with 33 age-matched control (AMC) children. DS serum immunoglobulin levels were compared with 962 non-DS children with recurrent infections. The results were combined with clinical data. Transitional and naive B lymphocytes are profoundly decreased in the children with DS. This could be caused by an intrinsic B-lymphocyte defect resulting in (partial) failure of B-lymphocyte generation, decreased antigen-induced proliferation and/or increased apoptosis, or by decreased proliferation due to deficient T-lymphocyte help, or a combination of these. The decreased CD27ϩ , CD21 high , and CD23 ϩ cells are reminiscent of common variable immunodeficiency and suggestive of disturbed peripheral B-lymphocyte maturation. Immunoglobulin levels in DS are abnormal-as has been described before-and different from non-DS children with recurrent infections. We conclude that the humoral immune system is abnormal in DS, but could not find a relation between B-lymphocyte subsets, immunoglobulins and clinical features of the children with DS in our cohort, nor could we answer the question whether DS lymphocytes are truly intrinsically deficient, or could all findings be explained by deficient Tlymphocyte help. (Pediatr Res 67: 563-569, 2010)

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“…This suggests that immunodeficiency may be an important component of DS (6). Abnormalities of cell-mediated, humoral, and phagocytic functions have been described in DS (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) but the findings have not been consistent. This inconsistency has been variously attributed to factors such as age variability between subjects and controls, institutionalization as a cause of exposure to frequent infections, and persistence of HBsAg in the blood of DS subjects (6,15,19,20).…”

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confidence: 99%

Age-Related Changes in Humoral and Cell- Mediated Immunity in Down Syndrome Children Living at Home

et al. 1987

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ABSTRACT. Abnormalities of humoral and cell-mediated TC, T cells immunity have been described in Down syndrome but HC, helper cells reported findings have been inconsistent. Confounding fac-SC, suppressor cells tors have included age, institutional versus home life, hepatitis B antigenemia, and zinc deficiency. To clarify this problem, we studied 64 children with Down syndrome (DS) compared with an age-matched control group. All children had always lived at home. All the DS children were negative for hepatitis B surface antigen. Serum zinc concentration in the DS group was on average 12 pg/dl lower than age-matched control children. They also had significantly lower levels of immunoglobulin M, total lymphocyte count, T and B lymphocytes, and T helper and suppressor cells. In vitro lymphocyte response to phytohemagglutinin and concanavalin A was significantly reduced at all ages in the DS group. Lymphocyte response to pokeweed mitogen increased with age in control children but decreased in the DS children. By 18 yr, the mean response for DS was 60000 cpm lower than controls. The DS group had significantly higher concentrations of immunoglobulins A and G than controls and the difference increased with age. Complement fractions C3 and C4 were also higher in the DS group at all ages. The number of HNK-1 positive cells was higher in the DS group than controls at all ages. When hepatitis and institutionalization are excluded a s confounding factors, DS children still differ in both humoral and cell-mediated immunity from an age-matched control group. (Pediatr Res 22: 536-540, 1987)

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Derangements of immunoglobulin levels, phytohemagglutinin responsiveness and T and B cell markers in Down's syndrome at different ages

Cited by 120 publications

References 18 publications

Both Normal Memory Counts and Decreased Naive Cells Favor Intrinsic Defect Over Early Senescence of Down Syndrome T Lymphocytes

Both Normal Memory Counts and Decreased Naive Cells Favor Intrinsic Defect Over Early Senescence of Down Syndrome T Lymphocytes

Down Syndrome B-Lymphocyte Subpopulations, Intrinsic Defect or Decreased T-Lymphocyte Help

Age-Related Changes in Humoral and Cell- Mediated Immunity in Down Syndrome Children Living at Home

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