Pediatric Hemophagocytic Lymphohistiocytosis - A Single Center Study

Objective: To describe the epidemiological features, outcomes and prognostic factors in diagnosis of pediatric hemophagocytic lymphohistiocytosis (HLH). Methods: 118 children fulfilling the inclusion criteria for HLH were identified from review of hospital records for period January, 2010 to December, 2019. Result: Median age at diagnosis was 4 years (range13 days-15 years). Presenting features were fever (100%), hepatosplenomegaly (91%), neurological symptoms (23%), bicytopenia (76%), transaminitis (67.3%), increased soluble interleukin-2 receptor) (sIL-2R) (78%) and hemophagocytosis on bone marrow (75%). Median follow-up duration was 13.5 months (3 days to 102 months). Primary HLH was identified in 27 (23%) patients. Etiology of secondary HLH was infections in 53 (45%), rheumatologic illnesses in 21 (18%) and malignancies in 8 (6%) children. Treatment modalities were steroid only (25%), anti-infectious agent (58%), multi-agent chemotherapy (43%) and HSCT (40%); mortality among above treatment groups were 25%, 58%, 43% and 40%, respectively. 15 patients (13%) had relapsed/refractory HLH who were treated with salvage chemotherapy and hematopoietic stem cell transplantation (HSCT). The overall mortality rate was 39%; mortality within 30 days seen in 23%. Estimated overall survival (OS) and event free survival (EFS) at 3 years were 62% and 61%, respectively. Conclusion: Pediatric HLH is an aggressive disease with high mortality. Hyponatremia, hyperbilirubinemia, coagulopathy and increased sIL2 receptor level at diagnosis predicts poor outcome.

Role of monitoring of bile soluble inhibitory receptor LAIR-1 and interleukin-2 receptor expression in liver acute rejection / 中华肝胆外科杂志

Objective Based on detection of the soluble LAIR-1 (sLAIR-1) and sIL-2R in the bile from recipient after liver transplant, the role of sLAIR-1 and sIL-2R in graft acute rejection were analyzed. Methods Bile sLAIR-1 level and sIL-2R were determined by double mAb sandwich enzyme linked immunosorbent assay in 55 cases of liver transplantation. Results In 22 recipients with normal graft function, sLAIR-1 and sIL-2R were detected at low level in the bile. In the 29 cases of liver acute rejection (AR), significant increase of bile sIL-2R level was detected on the lst and 2nd d before final diagnosis. With the effective methylprednisolone pulse therapy, sIL-2R level was decreased significantly on the 3rd d. On the other hand, remarkable increase of bile sLAIR-1 was found on the lst,2nd and 3rd d before final diagnosis. After of methylprednisolone pulse therapy for 3 d, bile sLAIR-1resturned to the control level. Conclusion Both bile sIL-2R and sLAIR-1 are detected at high level in the recipients suffering from liver acute rejection. The level of bile sLAIR-1 changes dramatically and responsively according to liver acute rejection. Therefore, detecting these two markers synergistically may be a promising monitor for rejection after liver transplantation.

Interleukin-2 receptor alpha expression in human retinal pigment epithelial cell / 眼科研究

Abstract Objective To investigate the expression of interleukin 2 receptor alpha (IL-2Rα) in human retinal pigment epithelial cell (RPE) and the effect of IL-2 on RPE proliferation. Methods Passage 2 -4 human fetal RPE cells were used in the experiment. RT-PCR was performed with the specific primer for IL-2Rα. IL-2 binding was assayed by fluorescence-activated cell sorting. Immunofluorescent staining was applied to identify the receptor expression using anti-CD25. The effect of recombinant IL-2 on RPE cell proliferation was determined by3H uptake. Results RPE cells expressed IL-2Rα mRNA. The expression of IL-2 receptor α was also revealed by immunofluorescent staining and IL-2 binding. IL-2 induced cell proliferation at the higher concentrations of IL-2 ( P＜0.05 ). Conclusion Cultured human RPE cells express IL-2α receptor. Recombinant IL-2 enhances RPE cell proliferation.

Studies on the Analgesic Effect of Polysaccharopeptide and Its Mechanism / 浙江中医药大学学报

[Objective]The study focus on the analgesic effect of polysaccharopeptide(PSP)and discuss the mechanism of this analgesia. [Methods]A total of 80 rats were divided randomly into high dose of psp,medium dose of psp,low doses of psp,positive control group,negative control group.After intragastric(ig) administration of different(high,medium and low)doses of PSP for 6 days,The tail stimulation-vocalization test was used to observe the analgesic effect of PSP.The IL-2 and IL-2R expression in mediobasal hypothalamus(MBH) was studied immunohistochemically.[Results]After intragastric(ig) administration of PSP for 6 days,the pain threshold was increased significantly and a dose-effect relationship was observed.After PSP administration the IL-2 expression in MBH was increased,while the IL-2R expression in MBH was decreased.[Conclusion]PSP has a definite analgesic effect and its analgesic site is in the MBH.The analgesia might be produced by the binding with the IL-2R in MBH by IL-2 secreted by T cells after PSP was injected into the brain.

EICOSAPENTAENOIC ACID ALTERS INTERLEUKIN-2 RECEPTOR DISTRIBUTION IN DETERGENT-INSOLUBLE MEMBRANE DOMAIN / 营养学报

Objective: To determine whether EPA exert effectively immunosuppressive function by altering distribution of IL-2R in membrane subdomains. Method: The human Jurkat E6-1 T cells were cultured in EPA-supplemented medium and the cells treated with stearic acid served as control. The effect of EPA on CD25 (IL-2? receptor) expression on the surface of T cells was investigated by flow cytometry. The lipid rafts were isolated by discontinuous sucrose density gradient ultracentrifugation. The localization of IL-2R?, IL-2R?, and IL-2R?c in fractions isolated and the effect of EPA treatment were determined by immunoblot and chemiluminescence. Results: EPA suppressed CD25 expression on the surface of T cells. IL-2R?, IL-2R?, and IL-2R?c were associated with lipid rafts of T cells, and these subunits were partly displaced from lipid rafts of EPA-treated T cells. Conclusion: Lipid rafts are functional subdomains for IL-2R signaling. EPA enrichment modifies distribution of IL-2R?, IL-2R?, and IL-2R?c in lipid rafts and EPA plays immunosuppressive roles probably by partly removing IL-2R from lipid rafts.

The Effects XGD-1 on the Proliferation of Human Peripheral Blood T Lymphocyte and the Expression of IL-2R / 中国普外基础与临床杂志

Objective To explore the immunosuppressive effect of XGD 1 and its mechanism. Methods Different concentrations of XGD 1 were added to PHA or ConA induced human peripheral blood T lymphocyte.Seventy two hours later modified MTT assay was employed to test the effect of XGD 1 on T cell proliferation. Flowcytometry was used to examine the effect of XGD 1 on the expression of IL 2 receptor(IL 2R) on the surface of T cells individually at 48 h and 72 h.And the effects of XGD 1 combined with cyclosporine A(CsA) on the proliferation of T lymphocytes and the expression of IL 2R were also investigated. Results In the concentration range of 0.2～25 ?g/ml,XGD 1 exerted marked inhibitory effect on PHA or ConA induced T cell proliferation,which was proportional to dose. Flowcytometry showed that XGD 1 inhibited the expression of IL 2R,and the percentage of IL 2R? positive cells after stimulation of PHA decreased from 47.67% to 25.03% in the presence of XGD 1 (1 ?g/ml).XGD 1 and CsA had synergism in inhibition of T cell proliferation and IL 2R expression. Conclusion The study suggests that XGD 1 has immunosuppressive effect. The suppressive effect of XGD 1 on T cell proliferation is most probably mediated by decreasing IL 2R expression.

Serum Levels of Soluble CD30 in Childrens with Atopic Dermatitis / 소아알레르기및호흡기학회지

PURPOSE: The pathogenesis of atopic dermatitis is not clearly defined yet, but the pathogenetic role of Th2 cells has been supposed. CD30 is a membrane-bound glycoprotein that may be expressed on activated T cells with a sustained expression in Th2 cells and can be released as a soluble form(sCD30). This study was done to document the changes of serum sCD30 and it's clinical significance in atopic dermatitis. METHODS: We analyzed serum sCD30, serum soluble IL-2 receptor (sIL-2R), total serum IgE and total eosinophil counts from 18 children with atopic dermatitis(AD), 15 atopic asthmatics without AD (AA), 15 atopic asthmatics with AD(AD+AA), and 14 healthy non atopics(control). We investigated the correlation of serum sCD30 levels with disease severity assessed by clinical scoring(SCORAD index) in the group of AD and AD+AA. RESULTS: The serum levels of sCD30 were significantly higher in the group of AD and AD+AA than the group of AA and control. There were no differences in serum sCD30 levels between the group of AA and control and between the group of AD and AD+AA. The serum sIL-2R levels showed no significant differences among the four groups. There was significant positive correlation between serum sCD30 and serum sIL-2R levels(P<0.05). Both serum sCD30 and serum sIL-2R levels showed no correlation with total serum IgE, total eosinophil counts, and disease severity, respectively. CONCLUSION: Serum sCD30 is elevated only in atopic dermatitis irrespective of presence of asthma. The results suggest that Th2 immune responses may involved the pathogenesis of atopic dermatitis and sCD30 may be the possible marker of atopic dermatitis.

Enhancement of proliferaton and tumoricidal activities of T-AK cells by plant polysaccharides / 中草药

Object To study the augmentation of the T activated killer (T AK) cell proliferating and tumor killing activities of the polysaccharide fraction from Rhodiola kirilowii (Regel) Regel, Lycium barbarum L., Hedysarum polybotrys Hand. Mazz., Glehnia littoralis F. Schmidt ex Miq., Rehmannia glutinosa (Gaert.) Libosch. ex Fisch. et Mey. and Aloe barbadensis Mill. in vitro. Methods The T AK cells were induced by anti CD 3 antibody (CD 3McAb) and rIL 2 from human peripheral blood mononuclear cells (PBMC). The effects of the above six plant polysaccharides (1～100 ?g/mL) on the proliferation of T AK cell, the cytotoxicity to Raji cells and L 1210 cells, and the IL 2 receptor (IL 2R) expression in T AK cells were determined. Results The six polysaccharides alone had no obvious effect on the proliferation of T AK cells. In the presence of rIL 2 and CD 3McAb, they could reinforce the proliferation of T AK cells and its tumor killing activities against Raji cells and L 1210 cells at a different extent, and a 21%～68% increase of IL 2R expression in T AK cells was observed. Conclusion The plant polysaccharides significantly enhance the proliferation and the tumoricidal activities of T AK cells and the enhancing actions related to the increase of IL 2R expression.

Requirements for in vitro growth of human thymocytes

Since it is difficult to study human thymocyte maturation in vitro, we have developed an in vitro thymocyte culture system which has allowed us to select the optimal growth conditions for thymocyte subpopulations. Three thymocyte subpopulations (CD3-CD1-, CD1+CD3-, and CD3+CD1-) were isolated by a single step percoll density gradient centrifugation and indirect panning procedure using anti-CD1 and anti-CD3 monoclonal antibodies, and their purity was checked by flow cytometry. The combination of concanavalin A (Con A), tetradecanoylphorbol acetate (TPA), and IL-2 was shown to be the most reliable stimulus for the proliferation of CD3-CD1- thymocytes for up to 15 days in a culture system in vitro. Flow cytometric analysis for the phenotypic change of CD3-CD1- thymocytes revealed a steady increase of CD3 antigen after a 3-day cultivation, whereas there was no change in CD1 antigen intensity. A combination of Con A and IL-2 was both sufficient and necessary to induce growth of CD3+CD1- thymocytes. The major population of immature cortical thymocytes (CD3-CD1+ or CD3+CD1+), which are considered to be the most unresponsive dead-end cells, could not be maintained or stimulated with any combination used in this experiment, even in the presence of thymic accessory cells.

SERUM SOLUBLE INTERLEUKIN-2 (IL-2) RECEPTOR LEVELS IN PATIENTS WITH LATE SCHISTOSOMIASIS JAPONICA / 中国血吸虫病防治杂志

The survey of the soluble IL-2 receptor (sIL-2R) level in the sera and the membrane IL-2 receptor (mIL-2R) expression on the peripheral blood mononuclear cells (PBMCs) from 47 cases of late schistosomiasis japonica was reported. The measurement for sIL-2R was done with the double antibody sandwich ELISA. Indirect immunflurescence was performed in the measurement for mIL-2R. The levels of sIL-2R in sera from 47 patients with late schistoso-miasis was found to be higher than that in control (P

Analysis of the Target Antigen Recognized By The Monoclonal Antibody (2H3) / 中国免疫学杂志

The McAb 2H3 to different target cells was investigated by using an indirect ELISA meth-ods. The result showed that the 2H3 could bind to the ConA actiuated mouse T lymphoblastsand CTLL-2 cells (an IL-2 dependent T cell line)but not to the resting mouse splenocytes,lymph node cells and thymocytes. The binding of FITC-anti-IL-2R to the activated mouse spleencells and CTLL-2 cells was seen as tested by immunofluorescence analysis. This binding reactionwas blocked when the target cells were previously treated with 2H3, but the binding reaction ofFITC-anti-Ia McAb to these target cells couldn't be blocded by 2H3. Further analysis of the tar-get antigen by using Western-Blotting technigue showed the molecular weight of this antihenrecognized by 2H3 was of 50～60KD in reducing condition. According to these data, target anti-gen recognized by the McAb 2H3 may be the IL-2R molecule(P_(55) mole cule)on the cell surface.

Establishment of a sandwich ELISA method for measuring soluble IL-2 receptor / 中国免疫学杂志

Two kinds of mouse monoclonal antibodies which recognize distinct epitopes of the IL-2 receptor (a chain) were used to establish a sandwich ELISA for measuring soluble IL-2 receptors. The results indicated that this method is sensitive and specific for detecting soluble IL-2 receptors of cell culture supernatant and serum from both healthy donor and patients with leukemia. Therefore this sandwich ELISA method is useful for basic and clinic immunology research.

Measurement of soluble IL-2 receptor by sandwich ELISA with monoclonal and polyclonal antibodies / 中国免疫学杂志

In this work, a simple and sensitive assay for soluble IL-2 receptor (sIL-2R) was established. The main procedures are as follows: the microplate was coated with anti-Tac monoclonal antibody (McAb); after sIL-2R in samples bound with the McAb, the rabbit anti-IL-2R serum was added;and HRP-goat anti-rabbit IgG was used to display and amplify this binding. The sensitivity of this method is about 100u/ml, which is near that in "Cellfree IL-2 Receptor Test Kit".

Interleukin-2 and its receptor abnormalities in Ankylosing Spondylitis and Rheumatoid Arthritis / 中国免疫学杂志

The production of IL-2 by peripheral blood lymphocytes from patients with Ankylosing Spondylitis (AS)and Rheumatoid Arthritis (RA) was compared with that of healthy controls. Patients with AS and RA showed a significant overproduction of IL-2.Membrane-bound IL-2 receptor was recognized by monoclonal anti-Tac antibody by using a flow cytometry. There was a marked increase of IL-2 receptor in patients with RA, while the level of IL-2 receptor in patients with AS was comparable to that of normal controls. The results suggested that there was obvious abnormalities of membrane-bound IL-2 receptor expressing and production of IL-2 in patients with AS and.RA which may contribute to the pathogenesis of these diseases.

Serum soluble IL-2 receptor level in patients with leukemia / 中国免疫学杂志

Serum soluble IL- 2 receptor (sIL-2R) level of 34 patients with leukemia were measured by ELISA. The sIL- 2 R levels are 296?99u /ml in normal, 660 ?449u /ml in AML, 1323 ?755 u/m in ALL, 1577 ? 759 u /ml in AMML and 1815 ? 858 u /ml in NHL. 5 of 6 patients with 2000u /ml sIL- 2 R died in one month after detection of sIL-2R. There is no apparent relationship between sII -2 R level and mononuclear cells count in peripheral blood. The results suggest that it is possible to be a new parameter for the observation and prognosis estimation to patients with leukemia by detection of sIL-2R.

High concentration IL - 2 induces the expression of IL - 2 receptor chian on resting PBL / 中国免疫学杂志

Using ~(125)I-labeled anti-IL-2R_? McAb, we investigated the effect of rIL-2 R_? expression . In addition to increasing the IL-2 R_? expression the actived-lymphoblasts, we found that the higher concentration of IL-2 also directly induced the IL-2 R_? expression on the resting PBL, but the peak was at the 5th day. After treated by a higher concentration of IL-2, there was a positive interrelation of time courses between the incorporation of ~3H-TdR and/or ~3H-UR and IL-2 R_? level on resting PBL. This result indicated that it was by means of inducing IL-2 R_? expression that the higher concentration IL-2 caused the proliferation of the resting PBL.