Clinical analysis of Belintoumab in the treatment of 10 children with acute B-lymphoblastic leukemia / 中华实用儿科临床杂志

Objective:To investigate the safety and efficacy of Belintoumab on the treatment of children with acute B-lymphoblastic leukemia (B-ALL).Methods:The clinical data of 10 children with CD 19+ B-ALL who were admitted to the Department of Pediatrics, the First Affiliated Hospital of Zhengzhou University from September 2021 to May 2022 and treated with Belintoumab were analyzed retrospectively. Results:Among the 10 cases, there were 6 recurrent cases, 3 cases with persistent minimal residual disease (MRD) positive after an initial treatment, and 1 case complicated with invasive candidiasis.Before treatment, bone marrow blasts ≥0.25, and that ranged 0.05-<0.25 were detected in 2 cases and 1 case, respectively.Seven cases had a complete remission (CR) of bone marrow, 6 of which were MRD positive and 1 case was MRD negative.After treatment with Belintoumab, the CR rate was 66.7% (2/3). The overall MRD negative rate was 88.9% (8/9), and the negative rate in previously MRD positive children was 100% (6/6). The median follow-up time was 4.1 (1.6-10.0) months after the application of Belintoumab.The overall survival (OS) rate was 70.0% (7/10). Eight MRD negative children received hematopoietic stem cell transplantation, and the OS rate was 75% (6/8). Survived children did not relapse until the last follow-up visit.Fever (90%, 9/10) was the most common adverse events, followed by neutropenia (90%, 9/10). One case (10%, 1/10) of neurotoxicity was seizures (grade 2) and one case (10%, 1/10) suffered cytokine release syndrome (grade 2), which did not influence the therapeutic efficacy of Belintoumab after symptomatic treatment.Conclusions:Belintoumab is safe and effective on the treatment of children with recurrent/refractory CD 19+ B-ALL, and those with MRD positive who have achieved CR in bone marrow have a higher rate of turning negative.Belintoumab can also be used as a bridge scheme for CD 19+ B-ALL children who cannot tolerate chemotherapy.

Efficacy analysis of blinatumomab in treatment of relapsed/refractory B-cell acute lymphoblastic leukemia / 白血病·淋巴瘤

Objective:To explore the efficacy and safety of blinatumomab in treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).Methods:The data of 8 patients with relapsed/refractory B-ALL treated with blinatumomab in Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from September 2020 to December 2021 were retrospectively analyzed, and their clinical characteristics, overall survival, lymphocyte subsets, cytokines, tandem transplantation and adverse reactions were analyzed.Results:The median follow-up time of 8 patients was 143 d (range: 41-534 d). Five of the 8 patients were alive; among them, 4 of 6 patients assessed to be in minimal residual disease (MRD)-negative complete remission (CR) and 1 of 2 patients assessed to be in non-remission at the time of belintuzumab discontinuation were alive. The median duration of treatment with belintuzumab was 28 d (10-56 d), and it was 23 d (10-56 d) for patients with MRD-positive at baseline and 28 d (25-31 d) for the 4 non-remission patients. Six patients achieved MRD-negative CR after treatment, of which 4 were assessed as MRD-positive at baseline and 2 were assessed as non-remission at baseline. All 4 patients with MRD-positive CR achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Philadelphia chromosome-positive (Ph +) ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph + ALL and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation and had persistent MRD-negative CR. Two of the 4 non-remission patients achieved MRD-negative CR after treatment with belintuzumab, including 1 patient with Ph + ALL bridged to autologous hematopoietic stem cell transplantation, and 1 patient with Ph - ALL received sequential allogeneic hematopoietic stem cell transplantation, and the 2 patients had persistent MRD-negative CR. Leukocyte counts and neutrophils decreased in both MRD-positive CR and non-remission patients after receiving belintumomab. The proportion and absolute number of CD3 + T and CD3 + CD8 + T lymphocytes in patients with MRD-positive CR were higher than those in patients without remission, and both decreased after drug administration. Median interleukin-6 (46.23, 1.42 pg/ml), interleukin-8 (17.85, 2.10 pg/ml), interleukin-10 (7.43, 1.49 pg/ml) and interferon-γ (11.82, 0.39 pg/ml) levels were elevated in MRD-positive CR and non-remission patients at week 3 of treatment. Grade 1 cytokine release syndrome occurred in 1 case with clinical manifestations of fever, which improved after drug suspension. Three cases developed infections, 2 of which were pulmonary and 1 of which was upper respiratory tract infection. No immune effector cell-associated neurotoxic syndrome was observed. Conclusions:Belintumomab is effective for MRD clearance in relapsed/refractory B-ALL with manageable adverse reactions, providing an effective therapeutic option for bridging hematopoietic stem cell transplantation to prolong the survival of patients.

B lymphocyte deficiency affects the structure of mouse heart and the composition of cardiac immune cells / 西安交通大学学报(医学版)

【Objective】 To explore the effect of B lymphocytes on cardiac structure and function and myocardial immune cells during heart development. 【Methods】 Echocardiography, immunofluorescence staining and flow cytometry were used to evaluate the composition of immune cells of the heart and the cardiac structure and function in wild-type (WT) mice and B-lymphocyte-deficient (μMT) mice, respectively. 【Results】 Compared with those of μMT mice, the ratio of heart weight to mouse weight (P<0.05), left ventricular mass (P<0.05) and the cross-sectional area of myocardial cells WT mice were significantly increased, while the ventricular ejection fraction was significantly decreased (P<0.05). The results of mRNA sequencing showed that WT mice and μMT mice differentially expressed genes were mainly enriched in the signal pathway of heart development and hypertrophic cardiomyopathy. The results of flow cytometry showed that WT mice had more Ly6g+ neutrophils, CD4+ positive T cells (P<0.001) and CD8+T cells (P<0.05) compared with μMT mice. 【Conclusion】 B-lymphocyte depletion alters the composition of cardiomyocyte immune cells, reduces left ventricular mass, and increases myocardial contractility.

MODY11 induced by heterozygous mutations of a novel B lymphocyte kinase / 中华内分泌代谢杂志

To characterize the clinical and molecular features of a patient with maturity-onset diabetes of the young 11(MODY11) and literature review. The patient was a 30-year-old female with hyperglycemia for 2 years. Failure to thrivea, primary amenorrhea, intellectual impairment, and severe hyperlipidemia were present at the same time. A novel mutations of the B lymphocyte kinase gene(BLK) c. 1025C>T(p.A342V) was found in the patient. Literature review revealed that there were more than ten mutation sites in BLK-MODY11. Some of them had hyperglycemia, over weight or systemic lupus erythematosus. To date, the clinical characteristics of the patient, such as growth retardation, primary amenorrhea, and intellectual impairment have not been reported in MODY11. Our clinical report further expands the clinical presentations and variabilities of MODY11.

Afectación de parámetros inmunológicos en un caso de leishmaniasis visceral autóctono del Noroeste Argentino / Alterations of immunological parameters in an autochthonous case of visceral leishmaniasis from the Northwest of Argentina

Resumen En el presente trabajo informamos la afectación de parámetros inmunológicos durante la etapa grave de la infección y luego de alcanzar la recuperación clínica en un paciente autóctono del Noroeste argentino con leishmaniasis visceral causada por Leishmania (Leishmania) infantum. Detectamos concentraciones plasmáticas elevadas de interferón-γ, interleuquina 10, IgG y BAFF (B-cell activating factor) durante la enfermedad activa, que se normalizaron luego de la recuperación clínica. En relación al perfil de diferenciación y memoria de las células T, clasificamos las células según la expresión de CD27, CD28, CD45RO, CD57 y perforina. Encontramos un fenotipo altamente diferenciado analizando la población de linfocitos T CD8+, con porcentajes aumentados de células T de diferenciación tardía y efectoras terminales. Si bien el fenotipo T CD8+ persistió luego de la recuperación clínica, pudimos observar un claro aumento de células T de memoria central en ese punto de estudio, sugiriendo signos de una posible reversión hacia un perfil T menos avanzado. El compartimiento de células B CD19+ mostró cambios más leves en la composición de las subpoblaciones de memoria. Documentamos el compromiso global de parámetros inmunológicos en la etapa grave de la leishmaniasis visceral que tienden a revertir luego de la recuperación, sugiriendo posibles signos de reconstitución inmune acompañando a la mejoría clínica. Los parámetros evaluados podrían ser útiles como biomarcadores de la evolución clínica de la enfermedad.

Abstract We report the alterations of immunological parameters of a patient with visceral leishmaniasis caused by Leishmania (Leishmania) infantum from the Northwest of Argentina during active disease and after achieving clinical recovery. We first demonstrated elevated amounts of IFN-γ, IL-10, B-cell activating factor (BAFF) and IgG in plasma during active disease, which returned to control values after recovery. In relation to T cell profile, we measured CD27, CD28, CD45RO, CD57 and perforin. We found a highly differentiated phenotype, preferentially in active disease and among CD8+ T cells, consisting in increased numbers of late differentiated and terminal effector cells. Although this highly differentiated CD8+ T cell phenotype persisted after recovery, a clear increase of central memory cells was recorded for both T subsets at that point, suggesting signs of reversion toward a less differentiated profile. The composition of the B cell compartment was slightly modified during active disease. Herein wedocument the global impact of severe visceral leishmaniasis on immunological parameters, which tend to revert upon clinical recovery, suggesting signs of immune restoration accompanying clinical improvement. The evaluated parameters could eventually be used as biomarkers of clinical evolution of visceral leishmaniasis.

Effect of CD20/CD19 bi-specific chimeric antigen receptor (CAR)-T cell on B lymphocyte tumor / 中国肿瘤生物治疗杂志

@# Objective: To design and prepare a novel bi-specific chimeric antigen receptor (CAR)-T cell targeting both CD20 and CD19 antigen on B lymphocyte surface, and to detect its killing effect on B lymphocyte tumors as well as its treatment efficacy on immunodeficiency B-NSG mouse with leukemia. Methods: Bi-specific CAR molecule of CD20 (human originated)/CD19 (murine originated) scFv was constructed and packaged into lentiviral vector in 293 cells, and then transfected into T lymphocytes from healthy donors to prepare BiCAR-T cells. K562-CD19-GFP cells (with positive CD19 expression), K562-CD20-GFP cells (with positive CD20 expression) and Nalm6-Luc-GFP cells expressing luciferase were constructed as target cells. After being co-incubated with above mentioned targets cells, the cytotoxic effects of BiCAR-T cells on target cells were evaluated via LDH release assay, and the secretion of IFN-γ by BiCAR-T cells was evaluated by ELISA. Nalm6-Luc-GFP cells were used to construct the mouse model of leukemia and BiCAR-T cells were transfused via tail veins; the treatment efficacy of BiCAR-T cells on tumor bearing mice was evaluated with small animal imaging method. Results: After 7 days’incubation, the BiCAR-T cells originated from healthy donors amplified about 20-50 times with a positive rate of 10%~92%, indicating successful preparation of BiCAR-T cells. Under an effector∶target ratio of 10∶1, the killing rates of BiCAR-T cells against Nalm-6, K562-CD19-GFP and K562-CD20-GFP cells were significantly higher than that of control cells [(76.7±7.4)% vs (8.7±2.4)%, (93.3±5.2)% vs (46.7±6.2)%, (51.0±0.8) vs (30.7±0.5)%, all P<0.01]. Compared with control group, BiCAR-T cells co-incubated with Nalm-6 cells also secreted significantly more IFN- γ [(872.7±7.7) vs (101.0±5.3) pg/ml, P<0.01). Animal experiment showed that BiCAR-T cells had significant efficacy on B-NSG mice with leukemia; NSG leukemia mice treated with BiCAR-T cells all lived up to 70 days (till they were mercy killed) and leukemia cells disappeared at about 50 days, while the mice in PBS and T lymphocytes group all died at (19±3) d and (20±1) d, respectively. Conclusion: Bi-specific CAR molecules expressing CD19 and CD20 were successfully designed and BiCAR-T cells were successfully prepared. The BiCAR-T cells can effectively kill CD19 and/or CD20 tumor cells and secret large amounts of IFN-γ after co-incubation with target cells, exerting significant treatment efficacy on B-NSG immunodeficiency mouse with leukemia.

Research progress on cardiac allograft vasculopathy / 器官移植

Allogeneic heart transplantation (HTx) is the primary treatment for patients with end-stage heart failure. Nevertheless, the long-term complication of cardiac allograft vasculopathy (CAV) after HTx is the main factor affecting the long-term survival of the recipients. Up to now, there is no effective methods to prevent and treat CAV. This article reviews the pathological manifestations of CAV, immunological factors of CAV and other risk factors of CAV, aiming to provide novel ideas and understanding for CAV research.

The role of CD28, CD40, CD45 RO and immunoglobulin G(FcyRI, FcyRII) in expression of T and B cells in mice / Монголын эм зүй, эм судлал

Purpose@#In generally, T cell activation evaluates by CD4 +, CD8 +, B cell immunoglobulin's (IgG, IgM, IgA) in Azathioprine caused secondary immunodeficiency in serum. May it does not make clearly interpret for regulation of cell-mediated and humoral immune response using interaction T and B cells. In this review, we discuss the multifaceted roles of cytokines as enhancers and expression of B and T cell. @*Cell-mediated Immunity and Humoral Immunity@#Based on the type of immunodeficiency, the types of defects can vary. While some bacterial infections may be a key feature of B cell and T cell defects are feature of combined T and B cell immunodeficiency. Also other defects can be cause of phagocytes cell and complement deficiency. The present study provides evidence special cytokines which are involved to expression of T and B cells that CD40, IgG, IgM, FcyRII (CD32) need to be define with B cell deficiency, CD40, CD45RO define combined T and B cell deficiency and FcyRI (CD64), CD45RO define for phagocytes cell deficiency and CD4+, FcyRI (CD32), FcyRI (CD64) define for complement deficiency. In this review, we have done pharmacological study of immunosuppressant injection which is with Mongolian <i>Astragalus Mongolicus</i> Bge and determined CD28, CD40, CD64, and CD45 cytokines in the blood serum of mice. It will be clarifying the immune system interaction between cell-mediated immunity and humoral immune for T cells and B cell interactions.

Advances in pathogenesis of minimal change nephrotic syndrome / 国际儿科学杂志

Minimal change nephrotic syndrome (MCNS) is the most common nephrotic syndrome among children.Although the details of pathogenesis remain unknown, it is widely considered that upregulated expression of T lymphocyte cell cytokines contributes to the initiation of MCNS.Moreover, studies had revealed that altered number and function disorder of B lymphocyte cells could change the functions of antigen presentation, participating in the onset of MCNS by affecting the function of T lymphocyte cells.Recently, CD80 has emerged as a popular research topic which exerts its effects via the change of podocytes morphology, thereby affecting the glomerular permeability.However, neither immune disorder nor podocyte dysfunction is poorly demonstrated to be associated with the pathogenesis of MCNS, the hypothesis such as "a 'two hit disorder" and "γδT cells exacerbate podocyte injury via the CD28/B7-1-phosphor-SRC kinase pathway" are raised.In the current review, we summarized the related investigations to help us to understand the mechanisms and pathogenesis of MCNS.

Advances in pathogenesis of minimal change nephrotic syndrome / 国际儿科学杂志

Minimal change nephrotic syndrome (MCNS) is the most common nephrotic syndrome among children.Although the details of pathogenesis remain unknown,it is widely considered that upregulated expression of T lymphocyte cell cytokines contributes to the initiation of MCNS.Moreover,studies had revealed that altered number and function disorder of B lymphocyte cells could change the functions of antigen presentation,participating in the onset of MCNS by affecting the function of T lymphocyte cells.Recently,CD80 has emerged as a popular research topic which exerts its effects via the change of podocytes morphology,thereby affecting the glomerular permeability.However,neither immune disorder nor podocyte dysfunction is poorly demonstrated to be associated with the pathogenesis of MCNS,the hypothesis such as "a two hit disorder" and "γδT cells exacerbate podocyte injury via the CD28/B7-1-phosphor-SRC kinase pathway" are raised.In the current review,we summarized the related investigations to help us to understand the mechanisms and pathogenesis of MCNS.

Immune complex inhibits toll-like receptor 9-activated JNK and p38 pathways in B lymphocytes / 第二军医大学学报

Objective To explore the inhibitory effect of immune complex (IC) on the signal pathways of high-expressed CD40 and CD80 induced by Toll-like receptor (TLR9) agonist CpG oligodeoxynucleotide (ODN) in B lymphocytes. Methods The mice were intraperitoneally injected with CpG ODN or IC plus CpG ODN, and the spleen CD19+ B lymphocytes were sorted by magnetic-activated cell sorting (MACS). The expressions of CD40 and CD80 on the B lymphocytes were detected by flow cytometry. The spleen B lymphocytes were isolated from wild type and immunoglobulin G Fcγ receptor Ⅱb (FcγRⅡb) knockout mice by MACS. After the isolated cells were stimulated with CpG ODN or IC plus CpG ODN in vitro, the phosphorylation levels of related protein kinases were detected in the B lymphocytes by Western blotting. Following CpG ODN stimulation, the B lymphocytes were treated with JNK p38 inhibitor SP600125 (50 μmol/L) or p38 inhibitor SB203580 (20 mg/L), and then the CD40 and CD80 expression levels on the CpG ODN-activated B lymphocytes were detected by flow cytometry. Results IC inhibited CD40 and CD80 expressions on the CpG ODN-activated B lymphocytes in vivo (both P0.05). IC inhibited the phosphorylation levels of JNK and p38 induced by CpG ODN in B lymphocytes, but did not inhibit them in the B lymphocytes from FcγRⅡb－/－ mice. The CD40 and CD80 expressions on the CpG ODN-activated B lymphocytes were significantly decreased after treated with SP600125 and SB203580 (both P0.01). Conclusion IC can inhibit the CD40 and CD80 expressions induced by TLR9 agonist CpG ODN through inhibiting the JNK and p38 pathways in B lymphocytes.

Clinical characteristics of high-grade B-cell lymphomas with rearrangement of MYC, bcl-6 and bcl-2 / 中华病理学杂志

Objective@#To investigate the clinicopathologic features of patients with high-grade B-cell lymphomas (HGBL) that have rearrangements of MYC, bcl-6 and bcl-2.@*Methods@#One hundred and fifty-eight B-cell lymphomas patients from Institute of Hematology and Blood Diseases Hospital from January 2016 to April 2017 were detected by fluorescence in situ hybridization (FISH) with double color split-apart probes.@*Results@#Among 158 B-cell lymphomas, 3 cases with MYC, bcl-2 and bcl-6 rearrangements were identified, 1 of which also had CCND1/IgH translocation. All three patients were of older age, with poor prognostic parameters, multiple organs involvements, elevated LDH and advanced-tumor stage. Two of the three patients were treated with high-intensity chemotherapy and had no remission with an overall survival of 9 months and 11 months respectively. One patient had follow-up with no treatment. Histologically, all three cases showed a spectrum of morphologic features. Although initially categorized as lymphoblastic lymphoma, diffuse large lymphoma and mantle cell lymphoma respectively, two cases were associated with germinal center B-cell (GCB) immunophenotype and 1 case with non-GCB immunophenotype. They had a high proliferation index as assessed by immunostaining for Ki-67 (60%-90%).@*Conclusions@#MYC+ bcl-2+ bcl-6+ HGBL is an aggressive disease with multiple organ involvement, high serum LDH levels, advanced stage disease, poor prognosis and shorter patient survival. The diagnosis should be made by histopathology combined with FISH analysis. Its separation from other types of B cell large cell lymphoma is of clinical importance.

Expression of IL-21/BCL-6/Blimp-1 in echinococcosis / 中国免疫学杂志

Objective:To study the expression of IL-21/BCL-6/Blimp-1 in CE patients and discusse the mechanism of the pathogenesis of the echinococcosis.Methods:27 patients and 30 health persons were collected from the first affiliated hospital of Xinjiang medical university in the same period.IL-21 was detected by ELISA and the expression of IL-21/BCL-6 /Blimp-1 mRNA was detected by Real-time fluorescence quantitative PCR (qRT-PCR) in CE patients.At the same time,17 patients were followed up in the group of patients,and the expression of IL-21/BCL-6/Blimp-1 was detected before and after treatment.Results:(1) The results of PCR showed that the levels of IL-21/BCL-6 mRNA were significantly increased in the peripheral blood mononuclear cells of the CE patients compared with the healthy control group (P<0.05).The expression of IL-21/BCL-6 /Blimp-1 mRNA in patients before the treatment was higher than that of patients after treatment(P<0.05).(2)The level of IL-21 in peripheral blood of CE patients was sig-nificantly higher than that in the healthy control group and basically returned to normal after the cure (P<0.05).IL-21 was positively correlated with BCL-6(r=0.733, P<0.01).Conclusion:BCL-6 and Blimp-1 May promote the human immune system to resist parasitic infection in the course of the development of the disease.IL-21, BCL-6 and Blimp-1 are significantly reduced after effective treatment,indicating that these factors are involved in the immune mechanism of the development of the disease.

Nursing of patients with B lymphocyte malignant tumor treated by CAR-T cell immunotherapy / 现代临床护理

Objective To summarize the experience of nursing the patients with B lymphocyte malignancies undergoing CAR-T cell immunotherapy. Method The nursing measures included nursing treatment and prognosis of 13 patients with B lymphocyte malignancies undergoing CAR-T cell immunotherapy at CAR-T cell transfusion, before and after transfusion. Results By careful treatment and care,11 of them were improved and discharged.2 cases complicated with severe CRS due to multiple organ failure,and died after rescue.There were no nursing related complications in 13 cases. Conclusion The nursing measures including full preparation,active nursing cooperation and effective treatment of complications are critical for the recovery of patients with B lymphocyte malignant tumor treated by CAR-T cell immunotherapy.

Clinical and laboratory characteristics of 11 cases of chronic B lymphocyte proliferation disease without lymphoid proliferation / 肿瘤研究与临床

Objective To explore the clinical and laboratory characteristics of chronic B lymphocyte proliferation disease (B-CLPD) without typical lymphoid proliferation. Methods The clinical records of patients with B-CLPD only characterized by pancytopenia form January 2007 to March 2016 in hematology department of Xinjiang Uygur Autonomous Region People ' s Hospital were collected, and the cell morphology, bone marrow pathology, cytogenetics and molecular characteristics were retrospectively analyzed. Results The median age of 11 patients was 68 years old. The lymphocyte ratio of peripheral blood smears in all patients increased in different level (0.36-0.68), but absolute lymphocyte count was normal or decreased (0.59×109-1.99×109). Lymphocyte-like plasma cell or small numbers of plasma cell can be seen in the bone marrow smears of 4 cases and lymphocytes with irregular burr-like protrusions were observed in 2 cases while there were no characteristic morphological changes in remained 5 cases. Immunophenotypical analysis showed that all patients expressed CD19, CD20, CD22, SmIg, not expressed CD5, CD10 which with scores of 0-2 according to chronic lymphocytic leukemia (CLL) points system;CD103, CD11C, CD25 and FMC7 were highly expressed in 2 cases while there were no characteristic expression in remaining cases. There were no abnormal karyotypes observed from the conventional cytogenetic and fluorescence in situ hybridization (FISH) analysis (both of IgH/CCND1, bcl-2/IgH were negative) in all patients. 8 patients were found IgH gene rearrangement, MYD88L256P and BRAF V600E was positive in 5 cases and 2 cases respectively. 5 cases were diagnosed as Waldenstrom macroglobulinemia, 3 cases were B-CLPD, 2 cases were hairy cell leukemia, 1 case was nodal marginal zone B-cell lymphoma after comprehensive analysis of their clinical and laboratory data. Conclusion Even if there are no increased peripheral blood lymphocytes in pancytopenia patients, it is necessary to perform bone marrow smears, immunophenotyping, IgH gene rearrangement, cytogenetics and other molecular laboratory tests to exclude B-CLPD, and reduce misdiagnosis.

Progress of B lymphocyte activating factor/a proliferation inducing ligand in Henoch-Schonlein purpura nephritis / 国际儿科学杂志

Henoch-schonlein purpura nephritis(HSPN) is the most common secondary glomerular disease in children.The pathogenesis of HSPN is unclear.In recent years,there have been some reports on B lymphocyte activating factor(BAFF) and a proliferation inducing ligand (APRIL),new members of the tumor necrosis factor family,as well as their association with HSPN.This paper reviews the related research from the following aspects:structure and biological functions of BAFF and APRIL,the role of BAFF/APRIL in the pathogenesis of HSPN,the prospect of BAFF and APRIL targeted biological agents in the treatment of HSPN.It provides a reference for further research on BAFF/APRIL system and HSPN.

Lymphocyte cells subtypes in hypertrophic adenoid in children with otitis media with effusion / 实用医学杂志

Objective To study the frequency of lymphocyte cells in hypertrophic adenoid in children with otitis media with effusion. Methods The study group consisted of 45 children suffering from hypertrophic adenoid coexisting with otitis media with effusion (HA/OME). The control group consisted of 34 children with adenoid hypertrophy(HA),but without otitis media. Adenoids excision was implemented. Cells were stained with fluorescently labeled protein-specific antibody. The lymphocyte of adenoids was determined by flow cytometry. Results Lymphocyte cells(CD3+CD4+CD69+T cells(1.29%),CD3+CD4+HLA-DR+T cells(0.61%),CD3+CD8+CD69+ T cells (1.39%),CD3+CD8+HLA-DR+ T cells (0.09%),CD19+CD69+ B cells (2.07%) and CD19+CD62L+B cells(0.21%)in HA/OME group were higher than in HA group:(CD3+CD4+CD69+T cells(1.94%), CD3+CD4+HLA-DR+T cells(0.84%),CD3+CD8+CD69+T cells(2.08%),CD3+CD8+HLA-DR+T cells(0.18%), CD19+CD69+ B cells (3.98%),CD19+CD62L+ B cells (0.46%). In addition ,there are the higher percentage lymphocyte cells(CD3+CD4+ T cells(8.97%),CD3+CD8+ T cells(4.27%),CD3+CD8+ Fas+ T cells(1.24%) and CD19+Fas+ B cells (3.23%) in HA/OME group than those in HA group:(CD3+CD4+ T cells (6.37%), CD3+CD4+CD69+ T cells (1.29%),CD3+CD4+HLA-DR+ T cells (0.61%) and CD3+CD8+ T cells(3.61%). Conclusions The local immune dysfunction resulting from hypertrophic adenoids may have a relationship with otitis media.

Molecular dynamics simulation and analysis of BAFF which is incorporated with p-nitro-L-phenylalanine / 中国药科大学学报

In order to study the structure-function relationship in the protein which is incorporated with p-nitro-L-phenylalanine,the method of MD(Molecular Dynamics) simulation was established and successfully used in the analysis of protein which contains p-nitro-L-phenylalanine.The force field of CHARMM can only stimulate protein with natural amino acid in NAMD.Compared with phenylalanine,p-nitro-L-phenylalanine just has one more group of nitro.If the parameter of group of nitro was defined,the protein containing p-nitro-L-phenylalanine can be simulated.CGenFF-paramchem was used to calculate the energy and topological structure of p-nitro-L-phenylalanine' s new bonds (r),angles (θ),dihendrals (φ) and improper angle (ψ).And then the new defined parameter and topology information was input into the related parameter files and topology files in CHARMM.On the basis of correct parameter,NAMD can successfully simulate the modified BAFF(B lymphocyte stimulator) which contains p-nitro-L-phenylalanine.The changes in structure indicated that there might be new B cell epitopes.The temperature distribution of each frame in the process of dynamics stimulation was in accord with normal distribution,which proved the defined force field parameters was feasible.The RMSD of whole protein solution systemis 2.5.Calculate each resides' RMSF in BAFF,the RMSF of p-nitro-L-phenylalanine's residue is 3.7,which is obviously higher than that of the other residues in β-pleated sheet,and close to the loop rings,indicate that there might be variation in the area of p-nitro-L-phenylalanine residue and might produce new comformational epitopes.The results of MD stimulation will guide the immunogenicity experiments of p-nitro-L-phenylalanine modified proteins.

Changes and significance of CD5+B lymphocyte in patients with systemic lupus erythematosus / 中华风湿病学杂志

Objective To measure the number of lymphocytes, B lymphocytes, CD5+B lymphocytes and level of IL-10 in peripheral blood of patients with systemic lupus erythematosus (SLE), and analyze their effects in the disease. Methods In this study, 84 cases of patients with SLE were randomly selected and evaluated according to the activity index (SLEDAI). These cases were divided into low activity group (SLEDAI0.05). In addition, the level of serum IL-10 in whether the low activity group (t=1.935, P=0.031) or the high activity group (t=3.048, P=0.012) was all higher than the normal control group. The level of serum IL-10 in patients with systemic lupus erythematosus was positively associated with SLEDAI score (r=0.425, P=0.024) and ESR (r=0.479, P=0.008), but was negatively correlated with complement 4 (r=-0.359, P=0.031). Conclusion The total number of lymphocytes in patients with SLE decreases significantly, while B lymphocytes increases significantly. The number of CD5+ B lymphocytes and the serum IL-10 level are also changed. It maybe related to the patient's inflammatory environment, and the number of CD5+B lymphocytes and the serum IL-10 level may be associated with disease activity.

Pathological damage of optic nerve in mice by the application of TACI-Ig / 上海交通大学学报（医学版）

Objective·To eliminate the effects of intraperitoneal injection of transmembrane activator and calcium modulator and cyclophilin ligand interactor-Ig (TACI-Ig) on the opitc neuritis and the integrity of myelin sheath in mice.Methods·Twenty-four C57BL/6J mice were randomly divided into 4 groups,which were blank control group,saline control group,low-dose (0.4 mg/kg) TACI-Ig group and high-dose (4 mg/kg) TACI-Ig group,with 6 mice in each group.All groups were received intraperitoneal injection every other day.The saline control group received 0.2 mL saline injection in the same way,and the blank control group was not given any intervention.After 20 d of treatment,the eyeballs and optic nerve tissues were collected from each mouse under anaesthesia,embedded in paraffin and stained with hematoxylin-eosin (H-E) and Luxol fast blue (LFB),respectively.Results·H-E staining indicated that optic nerve fibers arranged closely both in blank and saline control groups and the staining of tissues was uniform.The optic nerve structure of low-dose TACI-Ig group was similar to blank and saline control groups,while in high-dose of TACI-Ig group,the infiltration of inflammatory cells was observed.The inflammatory cell infiltration scores were not significantly different in all groups (P=0.610 3).The retinal structures of all groups were clear and distinct to observe,and single ganglion cells arranged tightly with complete cell shape,visible nucleus and uniform distribution.There was no difference in the retina structure among 4 groups.LFB staining indicated that there was no significant loss of the optic nerve myelin in 4 groups by microscope observation (P=0.473 6).Conclusion·Low-dose (0.4 mg/kg) TACI-Ig injection wouldn't damage the normal structure of optic nerves and retinal ganglion cells,meanwhile high-dose (4 mg/kg) of TACI-Ig injection might cause minor infiltration of inflammatory cells into retina.