Intrinsic abnormalities of lymphocyte counts in children with down syndrome

OBJECTIVE: Down syndrome (DS) is associated with an increased frequency of infections, hematologic malignancies, and autoimmune diseases, suggesting that immunodeficiency is an integral part of DS that contributes significantly to the observed increased morbidity and mortality. We determined the absolute counts of the main lymphocyte populations in a large group of DS children to gain further insight into this immunodeficiency. STUDY DESIGN: In a large group of children with DS (n = 96), the absolute numbers of the main lymphocyte subpopulations were determined with 3-color immunophenotyping using the lysed whole-blood method. The results were compared with previously published data in healthy children without DS. RESULTS: In healthy children with DS, the primary expansion of T and B lymphocytes seen in healthy children without DS in the first years of life was severely abrogated. The T- lymphocyte subpopulation counts gradually reached more normal levels with time, whereas the B- lymphocyte population remained severely decreased, with 88% of values falling below the 10th percentile and 61% below the 5th percentile of normal. CONCLUSIONS: The diminished expansion of T and B lymphocytes strongly suggests that a disturbance in the adaptive immune system is intrinsically present in DS and is not a reflection of precocious aging. Thymic alterations have been described in DS that could explain the decreased numbers of T lymphocytes, but not the striking B lymphocytopenia, seen in these children.     

Age-related changes in humoral and cell-mediated immunity in Down syndrome children living at home

Abnormalities of humoral and cell-mediated immunity have been described in Down syndrome but reported findings have been inconsistent. Confounding factors 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 micrograms/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 as confounding factors, DS children still differ in both humoral and cell-mediated immunity from an age-matched control group.     

Frequency of lower respiratory tract infections in relation to adaptive immunity in children with Down syndrome compared to their healthy siblings

Aim: Children with Down syndrome (DS) experience respiratory tract infections (RTIs) more frequently than healthy children. We investigated whether this is related to different immunological characteristics associated with DS. Methods: The study group consisted of 22 children with DS and 22 of their healthy, age‐range matched siblings. Data were collected on infections and hospitalizations because of lower RTIs. Immunoglobulin and IgG subclass levels in blood, as well as lymphocyte and T cell (subset) counts, were determined. Results: The children with DS had a significantly higher frequency of lower RTIs and related hospitalization than their siblings. We also found significantly reduced IgG2 levels as well as significantly lower counts of total lymphocytes, CD4⁺ T lymphocytes, CD4⁺ invariant natural killer (iNKT) cells and regulatory T cells in the DS group. Conclusion: In children with DS, reduced levels of IgG2, total lymphocytes, T lymphocytes, iNKT cells and regulatory T cells might contribute to their higher susceptibility to lower RTIs.     

T lymphocytes apoptosis and mitochondrial membrane potential in Down's syndrome

The increased susceptibility to infection, malignancies, and autoimmune disease, suggest that immunodeficiency is an integral part of Down's syndrome (DS). Little is known about the mitochondrial damage and tendency to apoptosis in peripheral T lymphocyte cells in DS. We studied 30 children with DS and 30 normal children, 15 of each group having no evidence of acute infection and 15 with acute infection. Potential apoptosis and membrane mitochondrial potential (MMP) were measured by flow cytometry. T lymphocytes in peripheral blood from DS patients do not display an increased tendency to undergo apoptosis, although a significant loss of MMP was found.     

不同年龄阶段小儿外周血B淋巴细胞CD21表达的差异

目的测定不同年龄阶段小儿外周血B淋巴细胞CD21表达水平,以探讨其临床意义。方法将住院非感染患儿分成新生儿组、婴幼儿组和儿童组,收集外周血1.8 mL,进行流式细胞仪检测,测定不同年龄组CD21的B淋巴细胞和CD21表达位点数目。结果1.新生儿外周血表达CD21的B淋巴细胞数目明显低于婴幼儿组和儿童组,且随年龄增长,其数值亦呈渐升高趋势。2.B淋巴细胞表达CD21平均荧光强度有渐增强特点。结论随小儿年龄增长,B淋巴细胞CD21表达渐上调,符合不同年龄段小儿免疫系统发育特点,也反映特定年龄段由于B淋巴细胞CD21高表达,而造成对EB病毒的易感性。     

Thymic deficiency in Down's syndrome.

Children with Down's syndrome (DS) often have small and abnormal thymuses, with lymphocyte depletion, diminution of the cortex, and loss of corticomedullary demarcation--a picture resembling thymic involution. Besides this, they have markedly enlarged Hassall's corpuscles, some surrounded by a sheath of lymphocytes. Patients with DS are known to have increased numbers of respiratory infections; they also have a higher incidence of lymphatic leukemia than do individuals who do not have DS. Studies of cell-mediated (thymic-dependent) immunity demonstrate that children with DS have both diminished numbers of T cells as well as functional deficiency of these cells.     

Immunodeficiency with recurrent panlymphocytopenia,impaired maturation of B lymphocytes,impaired interaction of T and B lymphocytes,and impaired integrity of epithelial tissue: A variant of idiopathic CD4+ T lymphocytopenia?

Idiopathic CD4⁺ T lymphocytopenia (ICL) has been defined as a cause of immunodeficiency with a variable clinical course and an unknown etiology. Here we describe a now 18‐year‐old boy with ICL, chronic mucocutaneous candidiasis (CMC), recurrent abscesses, and relapsing aphthous and ulcerous lesions. In addition to ICL the patient frequently showed a panlymphocytopenia. An increased percentage of γ⁺δ⁺ T lymphocytes and IgD⁺ IgM⁺ B lymphocytes, and a decreased percentage of CD21⁺ B lymphocytes, were observed. In vitro assays showed normal T‐cell responses to candidin and T‐cell mitogens, but impaired B‐cell responses to pokeweed mitogen (PWM). B‐cell maturation after stimulation with Staphylococcus aureus Cowan I (SAC) and interleukin 2 (IL‐2) was nearly normal. The clinical course of the patient improved substantially on administration of constant low‐dose therapy with fluconazole.     

Development of B lymphocyte function in childhood

The capacity of blood lymphocytes of children aged from birth to six years to produce immunoglobulins was studied in vitro at the cell level using a direct B lymphocyte activator (Epstein-Barr virus) or a T lymphocyte dependent B lymphocyte activator (pokeweed mitogen). Umbilical cord blood lymphocytes secreted IgM at adult levels after Epstein-Barr virus stimulation, while the ability to synthesize IgG and IgA increased up to the ages of 1 and 2 years, respectively, but not beyond this period. IgG3 production preceded that of the other IgG subclasses. The T lymphocyte dependent IgM synthesis was low at birth, but approached adult levels at two years of age. T cell dependent IgG and IgA secretion, however, remained reduced even up to 6 years of age.     

Development of B Lymphocyte Function in Childhood

ABSTRACT. The capacity of blood lymphocytes of children aged from birth to six years to produce immunoglobulins was studied in vitro at the cell level using a direct B lymphocyte activator (Epstein-Barr virus) or a T lymphocyte dependent B lymphocyte activator (pokeweed mitogen). Umbilical cord blood lymphocytes secreted IgM at adult levels after Epstein-Barr virus stimulation, while the ability to synthesize IgG and IgA increased up to the ages of 1 and 2 years, respectively, but not beyond this period. IgG3 production preceded that of the other IgG subclasses. The T lymphocyte dependent IgM synthesis was low at birth, but approached adult levels at two years of age. T cell dependent IgG and IgA secretion, however, remained reduced even up to 6 years of age.     

Peripheral blood lymphocyte subsets in children with frequent upper respiratory tract infections

It is a common and well-known fact that infants and preschool children undergo frequent episodes of upper respiratory tract infections. The majority of these children do not have a recognized immunodeficiency. The aim of the present study was to evaluate the effects of frequent upper respiratory tract infections on cellular immunity, using peripheral blood lymphocyte subsets and activation markers as defining parameters. The study group consisted of 16 children (aged 2-6 years) with frequent upper respiratory tract infections; 30 age-matched healthy children served as controls. Peripheral blood T, B, NK cells; T lymphocyte subsets; naive and memory cells; and activation markers were analyzed by using monoclonal antibodies and flow cytometry. White blood cell count (WBC) was found to be markedly increased in the study group compared to controls (p < 0.05). The absolute number of lymphocytes was also higher than that of the healthy children. The relative size of the CD3+CD8+ T lymphocytes and the relative and absolute numbers of CD3-CD16+56+ NK cells were found to be higher in patients than the controls. All the remaining percentages and numbers of the T cell subgroups including naive and memory cells and B lymphocytes did not show any difference, while CD3+CD25+ cell numbers were markedly increased (p < 0.05). In conclusion, the examination of peripheral blood lymphocyte subsets in children with frequent upper respiratory tract infections is important in evaluating cellular immune alterations due to antigenic stimulation; however, it is neither essential nor cost-effective in the management of the disease. This study has shown that both the percentage and absolute numbers of peripheral blood lymphocyte subsets maintain their normal status in children with frequent upper respiratory tract infections.     

Immunologic parameters in childhood Hodgkin's disease II. T and B lymphocytes in the peripheral blood of normal children and in the spleen and peripheral blood of children with Hodgkin's disease.

A study of peripheral blood lymphocyte populations in 27 children with Hodgkin's disease (HD) and 13 age-matched control subjects is presented. The absolute numbers and percentages of T and B lymphocytes identified by their surface marker characteristics were determined. In addition, in 13 HD children the percentages of T and B lymphocytes were estimated in the spleens removed at staging laparotomy. No differences were observed between the total peripheral blood lymphocyte counts of HD and control children, and we found no evidence of progressive lymphopenia with advancing stages of the disease. No decrease in the numbers of peripheral blood T lymphocytes was seen in this group of HD children. In contrast, the proportions and absolute numbers of B lymphocytes tended to be significantly lower in the children with HD than in the control subjects. In 9 of the 13 spleens studied high percentages of T lymphocytes were seen; low percentage of B lymphocytes were found in all spleens examined.     

Peripheral blood lymphocyte subsets in healthy Turkish children

Immunophenotyping of peripheral blood lymphocyte subpopulations is essential for the diagnosis and follow-up of children with immunodeficiencies and other immune disorders. The relative size and absolute number distributions (median and 5-95%) of lymphocyte subsets, including cord blood (Coulter, EPICS-XL) were examined by flow cytometry in 190 healthy subjects from birth to 18 years of age with a view to obtaining normal reference values for Turkish children of the following age groups: cord blood (n:29), birth to 1 year (n:41), 1 to 2 years (n:30), 2 to 6 years (n:30), 6 to 10 years (n:30), and 10 to 18 years (n:30). The relative size of CD2+, CD3+CD16-56-, CD3+CD8+ T lymphocytes increased while the relative size and absolute counts of those together with CD3+CD4+ and CD19+, CD20+ B lymphocytes decreased with age. The percentage of CD3-CD16+56+ NK cells increased from 0-1 year to 10-18 years; however, absolute count of CD3-CD16+56+ NK cells remained stable and unchanged in all age groups. The relative size and absolute count of activation markers (CD3+CD25+ and HLADR+) decreased from 0-1 year through 10-18 years age group. This study has once more demonstrated that both the percentage and the absolute number of lymphocyte subsets in cord blood and peripheral blood of healthy infants and children changed with age. Therefore, comparison of results to those of age-matched healthy controls is of utmost importance in the reliable and accurate evaluation of lymphocyte subsets reflecting cellular immunity in children.     

儿童肺炎支原体肺炎合并外周血淋巴细胞计数减少的临床分析

目的 探讨儿童肺炎支原体肺炎（MPP）合并外周血淋巴细胞计数减少的临床特征。方法 纳入2018年6月至2019年6月进行支气管肺泡灌洗的MPP住院患儿310例作为研究对象,包括单纯MPP患儿241例（未合并外周血淋巴细胞减少）,MPP合并外周血淋巴细胞减少患儿69例,比较两组患儿临床资料及治疗转归。结果 与单纯MPP组比较,MPP合并淋巴细胞计数减少组的热程和住院时间均较长,C反应蛋白、乳酸脱氢酶、支气管肺泡灌洗液中肺炎支原体DNA拷贝数值均显著升高（P < 0.05）。MPP合并淋巴细胞计数减少组肺实变、肺外并发症、支气管镜下严重病变（糜烂/痰栓）及重症MPP病例的发生率均明显高于单纯MPP组（P < 0.05）。结论 MPP合并外周血淋巴细胞计数减少患儿存在更严重的免疫损伤;外周血淋巴细胞数量可在一定程度上反映MPP的严重程度。     

过敏性紫癜表现及治疗效果与淋巴细胞凋亡的关系

目的通过观察79例过敏性紫癜(HSP)患儿治疗前后淋巴细胞凋亡情况,进一步阐明淋巴细胞凋亡(LA)在HSP中的表现及与各种治疗效果的关系。方法采用原位末端标记技术,对过敏性紫癜患儿治疗过程中淋巴细胞凋亡分组进行测定,在光学显微镜下观察,计算出凋亡比率,然后将急性期与正常组比较、病情较轻的HSP皮肤型与病情较重的HSP复合型比较、恢复期与正常组比较、常规方法治疗未愈的治疗前后比较、常规方法治疗及加用免疫抑制剂方法的治疗前后比较,各组均采用SPSS统计软件进行t检验统计学处理。结果发现急性期患儿组较正常对照组淋巴细胞凋亡情况有显著延迟(P<0.01),恢复期患儿组较急性期患儿组淋巴细胞凋亡情况有明显改善(P<0.01),恢复期患儿组与正常对照组淋巴细胞凋亡情况无明显的差异(P>0.05),经常规方法痊愈的HSP皮肤型淋巴细胞凋亡延迟情况已得到改善(P<0.01),但急性期未痊愈的HSP复合型淋巴细胞凋亡延迟情况未得到改善(P>0.05),急性期病情较重的HSP复合型较病情较轻的HSP皮肤型淋巴细胞凋亡延迟明显(P<0.05),应用雷公藤、激素、甲氨喋呤等免疫抑制剂后淋巴细胞凋亡加速(P<0.01)。结论急性期过敏性紫癜存在淋巴细胞凋亡的延迟,且症状较重HSP较症状较轻HSP的淋巴细胞凋亡延迟明显;经治疗达临床痊愈的恢复期过敏性紫癜淋巴细胞凋亡情况已达正常水平;常规方法治疗可使症状较轻的HSP淋巴细胞凋亡延迟得以改善,但对症状较重的复合型HSP的病例,须加用免疫抑制剂如雷公藤、激素、甲氨喋呤等使淋巴细胞凋亡加速,从而达到治愈目的。     

流式细胞术建立甘肃地区学龄前汉族儿童外周血淋巴细胞亚群相对计数的正常参考值范围

目的 建立甘肃地区学龄前汉族儿童外周血淋巴细胞亚群相对计数的正常参考值范围。方法 纳入2018年1月31日至2019年1月30日在甘肃省妇幼保健院(我院)行鞘膜积液、疝、血管瘤等手术或常规体检的0~7岁汉族健康儿童,排除患心脑血管疾病、血常规或肝肾功能异常、行淋巴细胞亚群检测前3周内存在感染、有先天性免疫缺陷疾病者。分为新生儿组、婴儿组、幼儿组和学龄前组。均采集静脉血2 mL(EDTA抗凝),于24 h内用四色荧光标记流式细胞术完成淋巴细胞亚群检测,以(P_2.5,P_97.5)作为各指标的正常参考值范围。结果 ①共792名儿童进入本文分析,男472名,女320名,新生儿组174名、婴儿组216名、幼儿组170名、学龄前组232名。②不同性别之间比较,新生儿组CD4⁺T细胞、CD8⁺T细胞、B细胞、NK细胞百分比和CD4⁺/CD8⁺比值差异有统计学意义,婴儿组CD4⁺T细胞、CD8⁺T细胞、B细胞百分比和CD4⁺/CD8⁺比值差异有统计学意义,学龄前组T细胞、CD4⁺T细胞、B细胞、NK细胞百分比差异有统计学意义。③男、女各年龄组组间整体比较,淋巴细胞亚群百分比差异均有统计学意义。T细胞、CD4⁺T细胞百分比随年龄增长呈降低趋势,男女童降低趋势相近;CD8⁺T细胞百分比随年龄增长呈升高趋势,女童增高趋势更明显;B细胞百分比在1岁前呈上升趋势,后呈降低趋势,女童的变化趋势较为缓和;NK细胞的变化与B细胞相反,在1岁内降低,而后升高,男童变化趋势更明显。结论 健康儿童淋巴细胞亚群的分布与地域、年龄段和性别有关。     

流式细胞术建立甘肃地区学龄前汉族儿童外周血淋巴细胞亚群相对计数的正常参考值范围

目的 建立甘肃地区学龄前汉族儿童外周血淋巴细胞亚群相对计数的正常参考值范围。方法 纳入2018年1月31日至2019年1月30日在甘肃省妇幼保健院(我院)行鞘膜积液、疝、血管瘤等手术或常规体检的0~7岁汉族健康儿童,排除患心脑血管疾病、血常规或肝肾功能异常、行淋巴细胞亚群检测前3周内存在感染、有先天性免疫缺陷疾病者。分为新生儿组、婴儿组、幼儿组和学龄前组。均采集静脉血2 mL(EDTA抗凝),于24 h内用四色荧光标记流式细胞术完成淋巴细胞亚群检测,以(P_2.5,P_97.5)作为各指标的正常参考值范围。结果 ①共792名儿童进入本文分析,男472名,女320名,新生儿组174名、婴儿组216名、幼儿组170名、学龄前组232名。②不同性别之间比较,新生儿组CD4⁺T细胞、CD8⁺T细胞、B细胞、NK细胞百分比和CD4⁺/CD8⁺比值差异有统计学意义,婴儿组CD4⁺T细胞、CD8⁺T细胞、B细胞百分比和CD4⁺/CD8⁺比值差异有统计学意义,学龄前组T细胞、CD4⁺T细胞、B细胞、NK细胞百分比差异有统计学意义。③男、女各年龄组组间整体比较,淋巴细胞亚群百分比差异均有统计学意义。T细胞、CD4⁺T细胞百分比随年龄增长呈降低趋势,男女童降低趋势相近;CD8⁺T细胞百分比随年龄增长呈升高趋势,女童增高趋势更明显;B细胞百分比在1岁前呈上升趋势,后呈降低趋势,女童的变化趋势较为缓和;NK细胞的变化与B细胞相反,在1岁内降低,而后升高,男童变化趋势更明显。结论 健康儿童淋巴细胞亚群的分布与地域、年龄段和性别有关。     

Cervical lymph node infections with non-tuberculous mycobacteria in preschool children: interferon gamma deficiency as a possible cause of clinical infection

Epidemiological studies have demonstrated a prevalence of positive PPD reactions to non‐tuberculous mycobacteria (NTM) in 9% of 4–5‐y‐old children in the Göteborg area. Very few children of this age develop suppurative infections in lymph nodes that require surgical procedures. The hypothesis was that these children might have T cell deficiencies with abnormalities of macrophage functions, particularly with type 1 cytokines. Twenty‐four children who needed operations were investigated immunologically and compared to 10 children of the same age operated on for non‐infectious reasons. The methods used were flow cytometry analysis of lymphocytes in blood, blood lymphocyte stimulation assays and interferon gamma analyses. The patients had significantly lower levels of interferon gamma than the controls after stimulation with Candida antigens or Con A. The numbers of T and B lymphocytes were higher in patients than in controls. Conclusion: Children with necrotic lymph node infections in the cervical region due to NTM had lower interferon gamma production after stimulation than healthy age‐matched controls.     

Immunological Reconstitution in Children After Completing Conventional Chemotherapy of Acute Lymphoblastic Leukemia is Marked by Impaired B‐cell Compartment

Humoral and cellular immunity were studied in 28 children completing conventional treatment of standard‐risk (SR) or intermediate‐risk (IR) acute lymphoblastic leukemia (ALL). Both naïve and memory B cells were most severely affected and showed slow recovery during the 2‐year follow‐up, while the T‐cell compartment showed only minor changes. Immunoglobulins and IgG subclasses, components, and antibodies against vaccine‐preventable diseases were not significantly affected. In conclusion, immune recovery after conventional chemotherapy for SR and IR ALL is marked by B‐cell depletion, but otherwise did not show any severe deficiencies in lymphocyte function.     

Recurrent wheeze in children with Down syndrome: is it asthma?

Aim: To compare the prevalence of current wheeze in children with Down syndrome (DS), their siblings, and nonrelated population controls. Methods: This was a case–control study in which the International Study of Asthma and Allergy in Childhood questionnaire for respiratory symptoms was completed by parents for 130 children with DS, 167 of their siblings, and for 119 age‐ and sex‐matched control subjects from the general population. Results: Both wheeze ever and wheeze during the last 12 months was more commonly reported in DS than in their siblings or controls. The relative risk (RR) of current wheeze in DS was 2.8 (95% CI, 1.42–5.51) compared with siblings, and 2.75 (95% CI, 1.28–5.88) compared with controls. A doctor’s diagnosis of asthma was found in 3.1% in children with DS, in 4.2% in siblings and in 6.7% in controls. During 4‐years follow‐up, the diagnosis of asthma could not be confirmed in the 24 DS children with current wheeze, and atopy was found in none of them. Conclusion: Wheeze is common in children with DS. This is likely to be related to the factors specific for DS and probably unrelated to asthma.     

Autologous stem cell transplant in a patient with Down syndrome and relapsed Hodgkin lymphoma

Children with Down syndrome (DS) are at increased risk for the development of acute leukemia but they rarely develop other hematologic malignancies or solid tumors. Despite aggressive supportive care, DS patients have increased risk of treatment related morbidity and mortality compared to other children. There are few reported cases of Hodgkin disease in children with DS, and no reported cases of successful therapy for patients with relapsed disease. We report on a child with DS and relapsed Hodgkin disease who was successfully treated with high‐dose chemotherapy and autologous stem cell transplant. Pediatr Blood Cancer 2009; 53:1327–1328. © 2009 Wiley‐Liss, Inc.