Nonspecific immunity in down syndrome: A study of chemotaxis, phagocytosis, oxidative metabolism, and cell surface marker expression of polymorphonuclear cells

Abstract

We have investigated several aspects of nonspecific immunity in Down syndrome (DS), utilizing peripheral polymorphonuclear leukocytes (PMNL), obtained from 12 children aged 8-16, diagnosed as trisomy 21, and their healthy matched controls. We used the under agarose method for chemotaxis assays, and flow cytometry for the determination of phagocytosis of monodispersed fluorescent beads, metabolic burst activity, and neutrophil surface marker expression on these cells. Our results indicate that a chemotactic defect exists in PMNL of DS children. However, no statistically significant differences were found between PMNL from DS children and those from controls in phagocytosis, oxidative burst, and expression of the markers CD11a, CD11b, CD16, and CD 18. Furthermore, no overexpression of CD11a and CD18 was present as a consequence of gene overdosage in PMNL from DS children. On the other hand, 3 different neutrophil subpopulations could be observed according to the CD16 staining pattern in DS children and controls; this might be a consequence of genetic variation or may represent different states of activation of these cells. Other factors such as T-cell involvement, and the role of cytokines, cyclic nucleotides, and zinc serum levels in DS patients should be further investigated in order to define the causes of the immunological derangement present in this condition.

Childhood and maternal infections and risk of acute leukaemia in children with Down syndrome: a report from the Children's Oncology Group

“…Children with DS are highly susceptible to infection and the tendency towards an impaired immune system has been well documented. Observed defects in immune function include decreased white cell counts, impaired cell-to-cell communication, reduced antibody levels, and abnormal lymphocyte function (Fong and Brodeur, 1987;Novo et al, 1993). In the presence of proliferative leukocyte stress provoked by infection, inherently abnormal leukocyte stem cells in patients with DS may be at increased risk of a second mutation resulting in leukaemia (Stewart, 1961).…”

Presenility of granulocytes in Down syndrome individuals

“…These associated disorders have been attributed to immunodeficiency and increased susceptibility to acute infections [Spina et al, 1981;Burgio et al, 1983]. In addition, decreased microbicidal activity [Novo et al, 1993] and deficient chemotaxis [Khan et al, 1975;Novo et al, 1993] in neutrophil functions are observed in DS patients. Increased morbidity of DS patients results from respiratory and gastrointestinal infections with a high incidence of heart failure and malignancy [Miller, 1971;Masaki et al, 1981].…”

Pandemic (H1N1) 2009 Virus and Down Syndrome Patients

“…Several risk factors for influenza also occur in Down syndrome patients ( 2 ): congenital heart disease in one half of patients ( 3 ), childhood obesity or excess weight in the majority ( 4 ), and a 8× higher prevalence of type 1 diabetes than in an age-matched control population ( 5 ). In addition, specific alterations in immune response are frequently present, including leukopenia, chemotactic defects ( 6 ), decreased immunoglobulin G 4 levels ( 7 ), and T- and B-cell abnormalities ( 7 , 8 ) with reduced B lymphocytes ( 9 ). Patients with Down syndrome have an increased need for hospitalization because of lower respiratory tract disease caused by respiratory syncytial virus ( 10 ) and other respiratory infections ( 11 ) as well as reduced access to healthcare ( 12 ).…”