Biomedical subjects

Syh-Jae Lin

Publications and source records attributed to Syh-Jae Lin.

13 recordsLinked to original sources

PubMed2006

Effect of interleukin-15 on alloreactivity in umbilical cord blood.

Interleukin(IL)-15 is a promising immunotherapeutic agent for immune reconstitution following stem cell transplantation. To investigate whether IL-15 would aggravate graft-versus-host disease (GVHD) in the setting of unrelated umbilical cord blood (CB) transplantation, we examined the effect of IL-15 on activation marker expression, proliferation and cytokine production of CB in a one-way mixed lymphocyte culture (MLC) assay. We found that IL-15 differentially enhanced CD69 and CD25 expression on CB T cells following allo-stimulation. The maximum degree of allo-specific CB proliferation was achieved on Day 6. IL-15 down-regulated the CB alloreactive proliferative response on Days 4, 6, and 8, with preferentially enhanced autologous proliferation. Exogenous IL-15 further enhanced CB TNF-alpha and IL-10 production in both autologous and allogeneic MLC 6 days after allopriming. Thus, IL-15 was effective in enhancing activation marker expression and cytokine production during CB alloreactivity, but failed to enhance allospecific proliferation. Further studies would be needed to study the role of IL-15 on GVHD in the setting of CB transplantation.

Antigens, CD↗

PubMed2006

Distribution, infections, treatments and molecular analysis in a large cohort of patients with primary immunodeficiency diseases (PIDs) in Taiwan.

One hundred and twenty-four patients (from 120 families) diagnosed as primary immunodeficiency diseases were enrolled from five tertiary medical centers. The distribution by an update eight categories showed 45 patients (13 females/32 males; 36.3%) with "predominant antibody deficiencies," 27 patients (6/21; 21.8%) with "T- and B-cell immunodeficiency," 25 patients (9/16; 20.2%) with "congenital defects of phagocyte," 25 patients (4/21; 20.2%) with "other well-defined immunodeficiency syndromes," one boy (0.8%) with "disease in immune deregulation" (Chediak-Higashi syndrome) and another with "complement 3 deficiency." None had "defects in innate immunity" or "auto inflammatory disorders." Pseudomonas and Salmonella spp. were the two most identified microorganisms in septicemia (39.7%; 27/68 episodes). Twenty-three patients (18.5%) had mortality. Stem cell transplantation succeeded in 7 of 12 patients. In addition to nine patients with DiGerge syndrome recognized by FISH, direct sequencing identified 12 unique mutations from 20 families, reflecting distinct Taiwan geography, although a selection bias may exist.

Child↗

PubMed2005

Differential effect of IL-15 and IL-2 on survival of phytohemagglutinin-activated umbilical cord blood T cells.

Cytokine immunotherapy using interleukin (IL)-2 and IL-15 may be beneficial for patients receiving umbilical cord blood (CB) transplantation by ameliorating post-transplant T-cell apoptosis. The present study compares the differential effect of IL-15 and IL-2 on survival of phytohemagglutinin (PHA)-activated CB and adult peripheral blood (APB) T lymphocytes. In comparison with IL-2, IL-15 preferentially enhanced the survival of CB PHA-activated T cells by decreasing the caspase-3+ population and by increasing the Bcl-2+ population. Activated CB T cells were more susceptible to TNF-alpha-induced apoptosis compared to their adult counterparts. However, the susceptibility could be abrogated by IL-15 but not by IL-2. IL-15 but not IL-2 down-regulated CD28 expression on both activated CB and APB CD8+ T cells, with a much greater effect seen with CB. Western-blot analysis shows that IL-15 Ralpha is deficient in CB compared to APB immediately after PHA stimulation, while culturing with IL-15 significantly enhanced CB IL-15 Ralpha expression to levels comparable to that of adults. Thus, IL-15 may provide a better therapeutic choice for immune reconstitution than IL-2 post-CB transplantation due to its preferential survival enhancing effect on CB T cells.

Apoptosis↗

PubMed2005

Distribution and clinical aspects of primary immunodeficiencies in a Taiwan pediatric tertiary hospital during a 20-year period.

Recent advances in immunologic techniques have lead to increased recognition of primary immunodeficiencies. A review of patients with suspected immunodeficiencies in a Taiwan tertiary hospital from January 1985 to October 2004 and molecular/genetic analyses done on some patients were investigated. Of the 403 patients selected based on the International Classification of Disease, Ninth Revision, 37 patients with PID (8 females and 29 males) were identified: 17 (46%) with antibody production deficiencies, nine (24%) with defective phagocyte function, four (11%) with combined B and T cell immunodeficiencies, seven (19%) with T cell deficiencies, but none with primary complement deficiencies. Those with secondary immunodeficiencies were excluded from the study. Recurrent sinopulmonary infections (62%) were the most common clinical manifestation, followed by sepsis (57%), severe skin infection (40%), splenomegaly/hepatomegaly (27%), central nervous system dysfunction (22%), chronic diarrhea (22%), and failure to thrive (19%). Seven (19%) patients died, five of infections, one of disseminated intravascular coagulopathy and one of hepatocellular carcinoma. Six novel mutations were found from 11 agreed patients. This is the first report on primary immunodeficiencies in Taiwan covering a 20-year period.

Adolescent↗

PubMed2005

Effect of FK506 on the interleukin 15-driven proliferation and apoptosis of anti-CD3-activated umbilical cord blood T cells.

BACKGROUND: Increased susceptibility of umbilical cord blood (CB) T cells to FK506 immunosuppression may contribute to the lessened severity of graft-vs-host disease in CB transplantation. OBJECTIVE: To investigate the FK506 sensitivity of interleukin 15 (IL-15)- and IL-2-driven proliferation and apoptosis of anti-CD3-stimulated CB T cells compared with adult peripheral blood (APB) T cells. METHODS: Surface flow cytometric analysis (CD25 and CD95), carboxyfluorescein diacetae succinimidyl ester staining to track CD3+ T-cell division, and flow cytometric analysis of apoptotic cell death using Annexin V were performed to determine the effect of FK506 on CD3+ T-cell activation and apoptosis after anti-CD3 stimulation in the presence of IL-15 or IL-2. RESULTS: IL-15 is superior to IL-2 in promoting CD25 expression and proliferation of anti-CD3-stimulated CB and APB T cells. Although IL-15-driven proliferation evaluated by carboxyfluorescein diacetae succinimidyl ester staining revealed comparable sensitivity to FK506 in anti-CD3-stimulated CB and APB T cells, IL-15-driven CD25 up-regulation in CB T cells was more sensitive to FK506 inhibition than APB T cells. FK506 down-regulated anti-CD3-induced apoptosis in CB and APB T cells (P < .01). However, the FK506 sensitivity of anti-CD3-induced T-cell apoptosis was lost in IL-15-supplemented CB cultures (P = .51) but not in corresponding APB cultures (P = .002). The IL-15-enhanced Fas expression on CB T cells (CD95) was decreased by FK506, similar to that observed with adults. CONCLUSIONS: We observed differential FK506 sensitivity of IL-15-driven CD25 up-regulation and apoptotic response comparing CB and APB T cells. This finding suggests the potential therapeutic benefit of FK506 in ameliorating graft-vs-host disease by decreasing IL-15-driven donor T-cell proliferation without inhibiting associated activation-induced apoptosis during CB transplantation.

Adult↗

PubMed2005

Epstein-Barr virus-associated infectious mononucleosis and risk factor analysis for complications in hospitalized children.

The characteristics of Epstein-Barr virus (EBV)-associated infectious mononucleosis (IM) in Chinese children are rarely reported. To evaluate the clinical presentations and risk factors for complications of EBV-associated IM in previously healthy children in Taiwan, hospitalized children with the diagnosis of IM due to EBV infection from January 1998 to December 2002 were enrolled. Patients had to fulfill the serologic criteria for the diagnosis of primary EBV infection [viral capsid antigen immunoglobulin M (IgM)-(+), viral capsid antigen IgG-(+), and anti-Epstein-Barr nuclear antigen (EBNA) antibody-(-) with exclusion of other concurrent infections or underlying diseases]. Ninety eight children were eligible, with 79% younger than 5 years old (mean, 4.0 +/- 2.3 years). The male-to-female ratio was 2:1. Nearly all patients suffered from fever (mean duration 10.3 +/- 6.0 days). Cough/rhinorrhea, tonsillopharyngitis, cervical lymphadenopathy and hepatosplenomegaly were found over half of the patients. Atypical lymphocytosis (mean, 12 +/- 13%) and elevated serum aspartate aminotransferase (AST; mean, 167 +/- 183 IU/L) and alanine aminotransferase (mean, 221 +/- 222 IU/L) were the most striking laboratory findings. Various complications, including hematologic, hepatobiliary, central nervous system, and obstructive airway problems occurred in about 20% of patients with significantly prolonged course of hospitalization. All patients recovered uneventfully under supportive and immunomodulating management. Female gender, no signs of tonsillopharyngitis, white blood cell count < or =10,000/mm3 and AST > or =150 IU/L were significant risk factors for the occurrence of complications. Clinicians should monitor such patients closely and give proper treatment to decrease possible morbidity or even mortality should complications occur.

Adolescent↗

PubMed2004

Evaluation of cytotoxic function and apoptosis in interleukin (IL)-12/IL-15-treated umbilical cord or adult peripheral blood natural killer cells by a propidium-iodide based flow cytometry.

Both deficient natural killer (NK) cell effector function and increased propensity to apoptosis of neonatal NK cells contribute to the increased susceptibility to infection in the neonates. Interleukin (IL)-12 and IL-15 are two immunoregulatory cytokines known to enhance cytolytic function of neonatal NK cells. The present study aims to simultaneously investigate the effect of IL-12/IL-15 on K562 cytotoxicity as well as NK cells apoptosis of enriched umbilical cord blood (CB) and adult peripheral blood (APB) NK cells, using flow cytometric cytotoxicity assays. The results indicated that (i) prior to cytotoxicity assays, CB NK cells underwent greater degree of spontaneous apoptosis than did APB NK cells; (ii) both IL-12 and IL-15 inhibited the spontaneous apoptosis of CB NK cells, while IL-15 promoted the apoptosis in APB NK cells; (iii) the deficient K562 cytotoxicity of CB NK cells could be enhanced to levels comparable with that of APB NK cells by IL-15; (iv) IL-15 increased the percentages of apoptosis in NK-K562 conjugates in a dose-dependent manner in both CB and APB with a greater effect seen with APB NK cells; (v) target-induced apoptosis was observed with APB NK cells which were further enhanced with IL-15. However, CB NK cells, unstimulated or IL-15-activated, were resistant to K562-induced apoptosis. Thus, the multi-parameter flow cytometry analysis not only demonstrates better for the deficient CB NK function but also provides greater details for cytotoxic mechanisms of NK cells.

Adjuvants, Immunologic↗

PubMed2003

Effect of interleukin-7 and -15 on activation of purified umbilical cord blood and adult peripheral blood CD4+ T cells.

We investigated the effect of two IL-2 receptor gamma chain (IL-2R-gammac)-signaling cytokines, IL-7 and IL-15, on the activation of purified CD4+ lymphocytes from umbilical cord blood (CB) and adult peripheral blood (APB) by assessing the expression of the IL-2 receptor-alpha (CD25) and Fas (CD95) on CD45RA+ (naïve) and CD45RO+ (memory) CD4+ subsets. Induced CD40L (CD154) expression following phorbol 12-myristate 13-acetate and ionomycin (P+I) stimulation was also examined on cultured CB CD4+ cells. Incubation with IL-15 at 10 ng/ml resulted in a significant increase in the mean fluorescence intensity (MFI) of CD25 on CB CD4+/CD45RA+ cells (exceeding those of APB) without affecting the percentage of CD25-expressing CD45RA+ cells (%CD25/CD45RA). In contrast, both CD25 MFI and %CD25/CD45RA were enhanced on IL-15-treated APB CD4+ cells. CD95 expression (both percent expression and MFI) on CB CD4+/CD45RA+ cells were also enhanced by IL-15, but to a lesser extent compared to the response of ABP. IL-7, used at a concentration equivalent to IL-15, had little effect on APB CD25/CD95 and CB CD25 expression, but did enhance %CD95 expression on CB CD4+/CD45RA+ cells. Both IL-7 and IL-15 could augment the P+I-induced CD40L expression on CB CD4+/CD45RA+ T cells. However, the enhancing effect of IL-15 on CB CD40L/CD45RA expression was more sustained than that of IL-7. Thus, our study demonstrated differential activation of CB CD4+/CD45RA+ cells in response to IL-7 and IL-15 compared to adult counterparts, and the different T-enhancing function between IL-15 and IL-7.

Adult↗

PubMed2003

Effect of interleukin 15 and interleukin 2 on anti-CD3-induced T-cell activation and apoptosis in children with common variable immunodeficiency.

BACKGROUND: Defective T-cell function and susceptibility to apoptosis following activation may contribute to the immunodeficiency observed in common variable immunodeficiency (CVID) patients. Interleukin (IL) 2 benefits CVID children by boosting T-cell function. OBJECTIVE: To investigate the effect of another IL-2 common gamma-chain signaling cytokine, IL-15, on T-cell activation and apoptosis of peripheral blood mononuclear cells (PBMCs) from children with CVID compared with IL-2. METHODS: Five children treated at the Chang Gung Children's Hospital, Taoyuan, Taiwan, during 1998 to 2002 who fulfilled World Health Organization criteria for CVID and 8 age-matched, healthy controls were enrolled. The PBMCs were stimulated with anti-CD3 in the presence or absence of IL-2 and IL-15 for 4 days, followed by 24-hour incubation with anti-Fas to induce apoptosis. Surface expression of CD69, CD25, and CD95 (Fas) on CD3+ T cells was evaluated by flow cytometry. The degree of apoptosis was evaluated by propidium iodide-phycoerythrin/annexin V-fluorescein isothiocyanate flow cytometric staining. RESULTS: Following anti-CD3 activation, CD69 and CD25 expression of CVID CD3+ PBMCs was enhanced to levels comparable to controls. Exogenous IL-15 resulted in further enhancement of anti-CD3-induced CD69 expression to a greater extent than that achieved with IL-2. A greater degree of apoptosis was found in CVID patients than controls following anti-CD3 stimulation (P = 0.001). IL-15 but not IL-2 further increased anti-CD3-induced apoptosis in control PBMCs (P = 0.001). In contrast, the degree of anti-CD3-induced apoptosis in CVID PBMCs was unaffected by IL-15 or IL-2. Addition of anti-Fas to cultures prestimulated with anti-CD3 further increased the apoptosis in control PBMCs but had no effect on apoptosis of CVID PBMCs. CONCLUSION: Comparable anti-CD3-induced activation and enhanced apoptosis were observed in PBMCs from children with CVID compared with controls. The degree of apoptosis in CVID PBMCs was not affected by exogenous IL-15 or anti-Fas, suggesting a preactivated status in vivo.

Adolescent↗

PubMed2003

Effect of interleukin-15 on anti-CD3/anti-CD28 induced apoptosis of umbilical cord blood CD4+ T cells.

OBJECTIVES: Interleukin-15 (IL-15) has potential therapeutic advantage for patients receiving umbilical cord blood (CB) transplantation. The present study aims to examine the ability of IL-15 to modulate the survival, maturation, and function of anti-CD3/anti-CD28 stimulated CB CD4+ T cells, in comparison with responses from adult peripheral blood (APB) CD4+ T cells. METHODS: Enriched CB and APB CD4+ T cells were stimulated with anti-CD3 and anti-CD28 (anti-CD3/anti-CD28) in the presence or absence of IL-15 (10 ng/mL) for 5 d. The percentages of apoptotic cells were assessed by propidium iodide/annexin-V flow cytometric staining. T-cell activation was analyzed with the expression of surface markers (CD45RO/CD69/CD25). Interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) production in culture supernatant was determined by enzyme-linked immunosorbent assay. RESULTS: CB CD4+ T cells had a higher survival and lower apoptotic response following anti-CD3/anti-CD28 stimulation, compared with APB CD4+ T cells. IL-15 enhanced apoptosis and promoted CD45RO conversion of anti-CD3/anti-CD28 activated CB CD4+ T cells, an effect not observed with APB CD4+ T cells. Although activated CB CD4+ T cells expressed comparable level of CD69/CD25 expression to adults, IFN-gamma production of activated CB CD4+ T cells was markedly deficient compared with that of corresponding APB CD4+ T cells. Exogenous IL-15 further enhanced the production of IFN-gamma, but not TNF-alpha, of activated CB CD4+ T cells. CONCLUSIONS: IL-15 preferentially resulted in an activation-enhancing effect on CB CD4+ T cells, accompanied by increased apoptosis. Our finding may have therapeutic implications while designing IL-15 immunotherapy for patients receiving CB transplant.

Adult↗

PubMed2003

TH1 and TH2 cytokine production among asthmatic children after immunotherapy.

Allergen immunotherapy results in a number of changes in clinical and immunological parameters. To study the kinetic influence of immunotherapy on cytokine production, we evaluated the ratios of Th1/Th2 for patients receiving mite-extract immunotherapy with 3-month intervals. Changes in Th1/Th2 ratio were calculated based on the intracellular cytokine and surface CD4 staining of peripheral blood mononuclear cells (PBMC). No significantly different Th1/Th2 ratios were detected after immunotherapy, although ratios were lower for asthmatic children when compared with normal controls. Cytokine production was also determined on supernatants from mite- or mitogen-activated PBMC cells. A significantly increased production of all cytokines was detected from activated PBMC from patients after immunotherapy. Thus hyposensitization with mite extract for 1 year might improve the cytokine production capacity of asthma patients' PBMC.

Allergens↗

PubMed2003

Hyper-IgM syndrome: a case report.

Hyperimmunoglobulin M syndrome is a rare primary immunodeficiency disorder. We report a case of a 6-month-old boy who suffered from developmental delays, frequent respiratory tract infection, and unusual fungal and bacterial infection. X-linked hyperimmunoglobulin M syndrome was ultimately diagnosed with decreasing immunoglobulin-G, A, and E (immunoglobulin G = 51.3 mg/dL, immunoglobulin A = 8.32 mg/dL, immunoglobulin E <17.5 mg/dL), elevating immunoglobulin M (immunoglobulin M = 140 mg/dL), and decreasing T-cell expression of the CD40 ligand over flow cytometry. Seizure episodes and hypotonia developed with greater signal intensity at the putamen in a brain magnetic resonance imaging, which is compatible with hypoxic ischemic encephalopathy. This is the youngest proven case of hyper-IgM syndrome in Taiwan ever reported.

CD4-Positive T-Lymphocytes↗

PubMed2003

Rotavirus gastroenteritis associated with afebrile convulsion in children: clinical analysis of 40 cases.

BACKGROUND: The purpose of this study was to evaluate the clinical manifestations and outcomes of hospitalized children with afebrile seizures following rotavirus gastroenteritis. METHODS: We conducted a retrospective study enrolling patients under 18 years old who were admitted to our hospital during a 10-year period with the diagnosis of rotavirus gastroenteritis. We identified and further analyzed patients who presented with afebrile seizures, without previous seizure disorders, electrolyte imbalances or hypoglycemia. The statistical methods used were the Chi-square test, the Kruskal-Wallis test and the Mann-Whitney test. RESULTS: Of 1937 patients, 40 patients (24 female and 16 male patients) met the inclusion criteria. The incidence of afebrile seizures following rotavirus gastroenteritis was 2.06%. The age of the patients ranged from 6 months old to 6 years old (mean, 1.9 years). The highest incidence of afebrile seizures was 4.67% in children 1 to 2 years of age (p < 0.001). Twenty-seven patients (67.5%) had two or more seizures, which usually were in clusters within a 24-hour period. No status epilepticus was observed. More than half of the patients (52.5%) suffered from seizures on the third day of diarrhea. Only five of 35 patients showed abnormal electroencephalogram (EEG) findings, which reverted to normal in four of the patients during the follow-up period. Most patients did not require long-term anticonvulsant treatment. During the follow-up period, all patients displayed normal psychomotor development without the recurrence of seizures, except in one patient who had a febrile convulsion. CONCLUSION: We found that the course of afebrile seizures following rotavirus gastroenteritis was benign with satisfactory outcomes.

Adolescent↗