Objective In order to identify abnormal mechanism of T cell regulation in the viewpoint of TCR/CD3 complex signal transduction, the effect of anti-CD3 antibodies, PMA and ionomycin on the proliferation, intracellular Ca 2+ concentration and PLCγ1 expression of neonatal umbilical cord blood lymphocytes was studied. Methods Differential antigen CD4, CD8 and CD2 expression on the surface of the CD3+ T cell from neonatal umbilical cord blood and adult peripheral blood were respectively examined with double staining-flow cytometry. DNA synthesis, intracellular Ca 2+ concentration and PLCγ1 expression of neonatal umbilical cord blood and adult peripheral blood lymphocytes treated by anti-CD3 antibodies, PMA and ionomycin were respectively detected with 3H-TdR incorporation method, spectrofluorometer and Western blot. Results CD3+ T cell ratio and its surface differential antigen CD4 and CD8 expression showed same pictures in neonatal umbilical cord blood and adult peripheral blood, but the surface adhesive molecular CD2 expression on CD3+ T cell in neonatal umbilical cord blood obviously increased than that in adult peripheral blood. DNA synthesis and intracellular Ca 2+ concentration of neonatal umbilical cord blood and adult peripheral blood lymphocytes treated by anti-CD3 antibodies, or combined PMA with ionomycin obviously increased. Also the DNA synthesis and intracellular Ca 2+ concentration in neonatal umbilical cord blood were lower than those in adult peripheral blood. However, compared with anti-CD3 antibody treatment, the proliferation induced by PMA combined with ionomycin in neonatal umbilical cord blood lymphocytes did not reach the level in adult peripheral blood lymphocytes. Before or after anti-CD3 antibody treatment, the PLCγ1 expression of neonatal umbilical cord blood lymphocytes was obviously lower than that of adult peripheral blood lymphocytes. Conclusion Neonatal T cell supplied a molecular basis for recognizing antigen and accepting co-receptor stimulation or co-stimulation. Signal transduction immaturity mainly occurred in the early stage of cell activation in neonatal umbilical cord blood lymphocytes. The cause of this immaturity may be related to decreased PLCγ1 expression, which was not effectively activated. [
Objective
More than one hundred primary immunodeficiency disorders have been discovered so far. But the incidence of these disorders in our country is still not clear, so we analyzed the clinical data of 93 children with primary immunodeficiency disorders seen in our hospital in recent 30 years to understand the occurrence of primary immunodeficiency disorders in children, to promote the clinicians to become familiar with these disorders, to improve the nationwide registry system and to establish the basis for the treatment and prevention in future.
Methods
To analyze the constituent ratio of the 93 children with primary immunodeficiency disorders seen in our hospital from 1974 to 2003, diagnostic and classification criteria were set by taking the proposal by International Union of Immunological Societies (IUIS)PID classification committee in 2003 into account. All the data were analyzed retrospectively.
Results
In the 93 children with primary immunodeficiency disorders, antibody deficiencies were the most frequent (39.8%) finding, followed by combined immunodeficiency, combined T- and B-cell disorders (22.6%), and T lymphocytic deficiencies alone (14.0%). Immunodeficiency with other major defects accounted for 12.9%, phagocytic disorders 9.7%, and complement deficiencies 1.1%. Thus, there seemed to be a tendency that the incidence increased with time. The incidence of these disorders has increased significantly as shown by 50 diagnosed cases in children with these disorders since 1996. Sixteen children died, with the highest mortality occurred with combined immunodeficiency. Seven children developed bronchiectasis. Two children suffered from persistent diarrhea while one of the two was complicated with persistent intestinal fistula. One child developed juvenile rheumatoid arthritis, another one with granulocytopenia and iridocyclitis, and the other with allergic purpura. The boys∶girls ratio for all disorders was 3∶1. The age of onset ranged from 10 days to 37 years of age.
Conclusions
There are vast variety of primary immunodeficiency disorders in our area and antibody deficiency is the most common abnormality. Combined immunodeficiency has early onset age and high mortality rate. With the great improvement of the diagnostic techniques, these disorders have become a group of important disorders and all the clinicians should pay great attention to these disorders.
Key words:
Immunologic deficiency syndromes; Retrospective studies
Objective To verify the relationship between transforming growth factor-β1(TGF-β1) and interleukin-10 (IL-10) in breast milk and allergic diseases development in infants. Methods Totally 191 mothers (99 allergics and 92 controls) and their full-term newborns participated in this prospective study on development of children atopy. Maternal blood, cord blood, colostrum and mature milk were assayed for TGF-β1 and IL-10 by enzyme-linked immunosorbent assay. Infants underwent pediatrician evaluation for allergic diseases at six months old. Concentrations of TGF-β1 and IL-10 from allergic and non-allergic mothers and prevalence of allergic diseases of infants were compared. Results The level of IgE in allergic mothers was 30 750 IU/L(6600-410000 IU/L),lower than that in non-allergic mothers[50000 IU/L(7100-610000 IU/L)](Z=-3. 444,P=0. 001).No difference in the concentration of TGF-β1, IL-10 and IgE in mature milk was observed between allergic and non-allergic mothers. TGF-β1, IL-10 and IgE levels in colostrum of allergic mothers were 2300 pg/ml(620-7000 pg/ml), 12. 8 pg/ml(7.5-560.0 pg/ml)and 7000 IU/L(5100-56000 IU/L),significantly higher than those in non-allergic mothers[1830 pg/ml(1240-9400 pg/ml), 11. 1 pg/ml (7. 2-630.0 pg/ml)and 6700 IU/L(5200-35000 IU/L)] (Z=-2. 215, -2. 730 and -2. 706,P＜0.05).In both allergic and non-allergic mothers, TGF-β1 and IL-10 levels in cord blood were higher than those in maternal blood, while IgE was lower. TGF-βl and IL-10 and IgE levels in colostrum were higher than mature milk(P＜0.05). At six months old, the prevalence of allergic diseases of infants from allergic mothers(59. 6%, 59/99) was significantly higher than those from non-allergic mothers (21. 7%, 20/92)(x2= 28. 177, P= 0. 000). The prevalence of allergic diseases of infants who completed two weeks' colostrum-fed after birth (44.5 %, 73/164) was significantly higher than those who did not (22.2%,6/27)(x2 =4. 749,P-=0. 029). Conclusions High concentration of TGF-βl and IL-10 in colostrum does not show any protective effect against allergic diseases in infants. The prevalence of allergic diseases of colostrum-fed infants is significantly higher than non colostrum-fed infants, showing that colostrum-fed might play a role in allergic diseases development.
Key words:
Hypersensitivity; Milk,human; Transforming growth factor betal; Interleukin10; Immunoglobulin E
The uncontrolled inflammatory response following infection is closely related to the morbidity and mortality of neonates. Interleukin 6 (IL-6) plays an important role in the pathogenesis and prognosis of this process. To better elucidate the secretion of IL-6 following infection in neonates, we investigated the IL-6 level and mechanism of IL-6/TLR4 signaling pathways.We compared the IL-6, procalcitonin (PCT), and CRP levels between septic neonates and toddlers. In vitro cord blood samples from healthy term neonates and peripheral venous blood from healthy adult volunteers were collected. Protein expression was analyzed by Western blotting, mRNA expression by real-time PCR and membrane molecule expression by flow cytometry.The IL-6 concentrations were significantly higher in the neonate group than in the toddler group (p < 0.05). In the toddler group, the IL-6 concentrations were correlated positively with both PCT and CRP (PCT: r = 0.451, p = 0.001; CRP: r = 0.243, p = 0.023). In vitro, the secretion of IL-6 increased with the rising concentrations of LPS; at 1000 ng/ml LPS, IL-6 secretion from the monocytes of neonates was significantly higher than that of adults. There was a marked decreased level of MyD88 in neonate monocytes compared with that in adult monocytes. Additionally, the mRNA levels of Zc3h12a in neonate monocytes were significantly lower than those in adult monocytes following LPS stimulation.Neonates displayed enhanced IL-6 production after infection. Our study, for the first time, reported a significant decrease in the expression of Zc3h12a in neonates. Thus, Zc3h12a may be a key factor for the aberrant increase in IL-6 after neonate infection.
OBJECTIVE: Epstein-Barr virus (EBV) is a ubiquitous human γ-herpes virus, which can adapt and evade host immune defense. Dendritic cells (DCs) play a pivotal role in the initiation and maintenance of immune responses. This study investigated the effects of EBV on cord blood monocytes derived DCs (CBDC). METHODS: Monocytes were isolated from cord blood and cultured in medium containing recombinant IL-4 and GM-CSF to induce DCs development. B95-8 supernatant was added in monocytes culture medium for EBV infection at day 0. Phenotypic characterization of DCs, apoptotic cells, and mitochondrial membrane potential (MMP) were detected by flow cytometry. The morphology was observed by Hoechst 33258 staining and TUNEL staining, the expression of X-linked inhibitor of apoptosis protein (XIAP) was detected by Western blotting assay and caspase 3, 8 and 9 activity was measured. RESULTS: Phenotypic characterization of DCs was changed in EBV-treated group. Chromatin condensation and DNA fragmentation were observed in EBV induced CBDC apoptosis. In addition, caspase 3, caspase 8, and caspase 9 activation were enhanced in the EBV-treated group. This was accompanied by the loss of MMP. Furthermore, XIAP expression was down-regulated in the EBV-treated group and compared to mock-infected group. CONCLUSION: These results suggested that EBV could inhibit CBDC phenotypic differentiation, and induce CBDC apoptosis in caspase-dependent manner with involvement of the mitochondrial pathway. This might help EBV to evade host immune responses to establish persistent infection.
Objective To explore the changes of serum level of interleukin-17(IL-17) in different stages of Henoch-Schonlein purpura(HSP) in children and its clinical significance.Methods Forty-one children with HSP were selected from Sep.2009 to Dec.2009.The serum concentration of IL-17 was measured by enzyme linked immunosorbent assay(ELISA) in acute stage and remission stage of HSP,and 20 healthy children were studied as healthy control group.The data were analyzed by SPSS 11.0 software.Results Serum level of IL-17 in acute HSP was significantly lower than that in healthy control group(t=-4.156,P0.01)and also was significantly lower than that in remission stage(t=-3.993,P0.01).Serum level of IL-17 in remission stage had no significant difference compared with that in healthy control group.According to different clinical types,the serum level of IL-17 had no difference in statistics,except for children with severe gastrointestinal hemorrhage,the level of IL-17 in acute stage was significantly higher than that in healthy control group.Serum level of IL-17 in acute had a positive correlation with immunoglobulin G(IgG)(r=0.564,P0.01),C-reactive protein(CRP)(r=0.545,P0.01),urine microalbumin(r=0.681,P0.01) and urine transferrin(r=0.471,P0.01).Conclusions T cells maybe involved in the pathophysiology of HSP.The changes of serum level of IL-17 reflect pathogenetic condition,so it may provide clinical clues for the inchoate diagnosis of HSP nephritis.
To investigate the major allergens in children with different allergic diseases, and to provide theoretical evidence for the clinical prevention, diagnosis, and treatment of allergic diseases in children.Skin prick test (SPT) was conducted to detect allergens in 1179 allergic children. According to clinical diagnoses, patients were categorized into six groups: atopic dermatitis (n=140), allergic gastroenteritis (n=37), allergic conjunctivitis (n=77), asthma (n=285), allergic rhinitis (n=301) and allergic co-morbidity (n=329) groups.Of the 1179 patients, 82.0% had positive SPT results; the most prevalent inhalant allergens were Dermatophagoides farinae (68.1%) and Dermatophagoides pteronyssinus (53.5%), while the most common food allergens were milk (5.0%) and eggs (4.8%). The proportions were 84.3% and 83.8% for patients under or equal to 3 years of age in the atopic dermatitis and allergic gastroenteritis groups, respectively. Patients over 4 years of age accounted for the majority of the other four groups. Food as major allergens were found in both atopic dermatitis and allergic gastroenteritis groups; eggs and Dermatophagoides farinae were the most common allergens for the former group, while eggs and milk for the latter group. Inhalant allergens were the major allergens in the allergic conjunctivitis, allergic rhinitis, asthma, and allergic co-morbidity groups, and the most prevalent allergens were Dermatophagoides farinae and Dermatophagoides pteronyssinus.There are differences in the distribution of age and allergen types in children with different allergic diseases. Atopic dermatitis and allergic gastroenteritis are prevalent in infants and young children, and food allergens are more common. Patients in allergic conjunctivitis, allergic rhinitis, asthma, and allergic co-morbidity groups are mostly children over 4 years of age, and inhalant allergens are more common.
Immunoglobulin A (IgA) is the most abundant antibody isotype in the mucosal immune system. Structurally, IgA in the mucosal surface is a polymeric structure, while serum IgA is monomeric. Secretory IgA (sIgA) is one of the polymeric IgAs composed of dimeric IgA, J chain, and secretory component (SC). Most of sIgAs were generated by gut and have effects in situ. Besides the function of "immune exclusion," a nonspecific immune role, recent studies found it also played an important role in the specific immunity and immunoregulation. Thanks to the critical role of sIgA during the mucosal immune system homeostasis between commensal microorganisms and pathogens; it has been an important field exploring the relationship between sIgA and commensal microorganisms.
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