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Objective:To prepare 89Zr labeled Daratumumab and evaluate its feasibility in the imaging diagnosis of multiple myeloma (MM). Methods:According to the principle of 89Y (p, n) 89Zr nuclear reaction, 89Zr was produced by cyclotron solid target system (30 μA, 1.5 h) and automatic purification module. The radionuclide purity, half-life and impurity metal ion concentration were detected. Desferrioxamine (DFO) was coupled with Daratumumab and then chelated with 89Zr to prepare 89Zr-DFO-Daratumumab. The quality control analyses of three consecutive batches were carried out. Pharmacokinetic evaluation and 89Zr-DFO-Daratumumab microPET/CT imaging were performed in normal rabbits and orthotopic myeloma mouse models, respectively. The SUV in situ myeloma and that in normal bone were compared by independent-sample t test. Results:About 560 MBq of 89Zr was obtained, and there were only two characteristic energy peaks of 89Zr (909 keV and 511 keV) by γ spectrometer. The half-life of 89Zr was 78.2 h, and the content of metal impurities was small. 89Zr-DFO-Daratumumab was prepared with pH of 7.2, radiochemical purity of more than 99%, good stability in vitro, and sterility and endotoxin tests were passed. Pharmacokinetic studies in rabbits showed that 89Zr-DFO-Daratumumab was gradually distributed from blood to liver, spleen, kidney and bone joints over time and metabolism. The results of microPET/CT imaging in orthotopic myeloma mouse models showed that the SUVs of 89Zr-DFO-daratumumab in situ myeloma were significantly higher than those in normal bone (2 h: 0.22±0.02 vs 0.06±0.00; 1 d: 0.38±0.01 vs 0.08±0.00; t values: 8.89, 21.90, both P=0.001). Conclusion:89Zr and 89Zr-DFO-daratumumab are successfully prepared, and relevant quality control and biological evaluation in vivo and in vitro are completed, which verify the feasibility of 89Zr-DFO-Daratumumab in the imaging diagnosis of MM, thus laying a foundation for clinical transformation.
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Objective The plasma levels of interleukin 6 (IL-6),high sensitive C reactive protein (hs-CRP) and the level of T cell activation were detected in the peripheral blood inflammatory factors of acquired immunodeficiency syndrome (AIDS) patients,and the relationship with opportunistic infection and prognosis was analyzed.Methods 79 human immunodeficiency virus (HIV)-positive/aids cases from May 2014 to January 2015 in first hospital of Changsha were enrolled in the study.They were divided into three groups:HIV-infected without opportunistic infections group (n =20),HIV-infected with infections group (n =43,including HIV-infected with tuberculosis group,HIV-infected with merge fungus group.HIV combined hepatitis C),death group (n =16).Serum IL-6 and the concentration of hs-CRP were detected by enzyme-linked immunosorbent assay (ELISA).Flow cytometry was used to test the CD3 + CD4 + cell count,the percentage of CD4 + CD38 + cell and CD8 + CD38 + cell in peripheral blood mononuclear cell (PBMC).Compare the differences among the three groups.Results The results showed that:the concentration of hsCRP and IL-6 in peripheral blood of HIV death group was significantly higher than that in other three groups (P ＜ 0.05).The concentration of hs-CRP and IL-6 in the peripheral blood of the HIV-infected with tuberculosis group and HIV-infected with merge fungus group were significantly higher than that in the HIV-infected without opportunistic infections group (P ＜ 0.05),and the hs-CRP in the peripheral blood of the HIV combined with the hepatitis C group was higher than that in the HIV-infected without opportunistic infections group (P ＜ 0.05).The number of CD3,CD4T lymph nodes in the death group and the combined opportunistic infection group was significantly lower than that in the HIV-infected without opportunistic infections group (P ＜ 0.05).The HIV-RNA expression in peripheral blood of the death group and the combined opportunistic infection group was significantly lower than that in the HIV-infected without opportunistic infections group (P ＜ 0.05).The expression of CD8+CD38+ on PBMC in the HIV-infected without opportunistic infections group was significantly lower than that in the death group,the tuberculosis group,the fungus group and the hepatitis C group (P ＜ 0.05).The expression of CD4+ CD38 + on PBMC in the HIV-infected without opportunistic infections group was higher than that in the death group (P ＜ 0,05).Conclusions The concentration of inflammatory cytokines (IL-6,hs-CRP) and the expression level of T cell surface CD8 + CD38 + related to immune activation were associated with opportunistic infection and prognosis of AIDS.
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Biliary atresia (BA) is one of the most serious pediatric surgical digestive system diseases with progressive liv?er bile duct inflammation and fibrous obstruction. Currently, the etiology of BA is not clear. It may be associated with genetic predisposition, viral infections and immune injury. Now many scholars believe that it was resulted from multiple factors. Among them, the theory of immune-inflammatory is supported by most scholars. Now the mechanisms of CD38, CD138 and IgG4 in autoimmune liver disease were reported in literature. BA and other autoimmune liver diseases are similar in terms that both inflammatory and immune responses plays irreplaceable role during disease development. Therefore, this article briefly review the role of CD38, CD138 and IgG4 in the inflammation-immunity of BA.
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Objective To explore the CD38 expression in T-cens(CD38-T)of chronic lymphocytic leukemia(CLL).Methods Multi-parameter flow cytometry was used to detect the expression of CD38,ZAP-70 and CD4/CD8 in 83 CLL patients.Results CD38 was positively expressed in 49.4%(41/83)T-cells(CD38-T)and 50.6%(42/83)tumor cells(CD38-B)of all CLL patients.The expression of the CD38-T was highly correlated with CD38-B(r=0.553,P＜0.01).ZAP-70+CD38+-T and ZAP-70-CD38-T constituted 67.5%(56/83)of CLL patients.There was significant correlation between CD38-T and ZAP-70 (r=0.349,P＜0.01).There was 33.3%(14/42)patients with CD38-T in Binet A patients,and 65.9% (27/41)in Binet B+C patients.There was also significant correlation between CD38-T and Binet B+C(r=0.312,P＜0.05),and CD4/CD8(r=0.453,P＜0.05).Conclusions Aberrant expression of CD38 in T-cells might be of prognostic relevance in CLL Most of the patients with high level CD38-T expression are accompanied with disorder or imbalance of immune function.CD38 expression in T cells might be a new prognostic factor in CLL.
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ADP-ribosyl cyclase (ADPR-cyclase) produces a Ca2+-mobilizing second messenger, cyclic ADP- ribose (cADPR), from beta-NAD+. A prototype of mammalian ADPR-cyclases is a lymphocyte antigen CD38. Accumulating evidence indicates that ADPR-cyclases other than CD38 are expressed in various cells and organs. In this study, we discovered a small molecule inhibitor of kidney ADPR-cyclase. This compound inhibited kidney ADPR-cyclase activity but not CD38, spleen, heart or brain ADPR-cyclase activity in vitro. Characterization of the compound in a cell-based system revealed that an extracellular calcium-sensing receptor (CaSR)- mediated cADPR production and a later long-lasting increase in intracellular Ca2+ concentration ([Ca2+]i) in mouse mesangial cells were inhibited by the pre-treatment with this compound. In contrast, the compound did not block CD3/TCR-induced cADPR production and the increase of [Ca2+]i in Jurkat T cells, which express CD38 exclusively. The long-lasting Ca2+ signal generated by both receptors was inhibited by pre-treatment with an antagonistic cADPR derivative, 8-Br-cADPR, indicating that the Ca2+ signal is mediated by the ADPR-cyclse metabolite, cADPR. Moreover, among structurally similar compounds tested, the compound inhibited most potently the cADPR production and Ca2+ signal induced by CaSR. These findings provide evidence for existence of a distinct ADPR-cyclase in the kidney and basis for the development of tissue specific inhibitors.
Subject(s)
Rats , Mice , Humans , Animals , Receptors, Calcium-Sensing/metabolism , Rats, Sprague-Dawley , Kidney/enzymology , Enzyme Inhibitors/chemistry , Cyclic ADP-Ribose/metabolism , Cell Line , Calcium Signaling , Azo Compounds/chemistry , ADP-ribosyl Cyclase/antagonists & inhibitorsABSTRACT
AIM: To investigate the expression of B lymphocyte stimulator(BLyS) and CD38 molecules on peripheral blood lymphocytes of patients with systemic lupus erythematosus(SLE). METHODS: Twenty-two patients with SLE and fourteen healthy subjects entered the study. Isolated peripheral blood lymphocyte were stained for the lymphocyte surface markers BLyS, CD19, and CD38, and then was measured by flow cytometry(FACS). RESULTS: BLyS + lymphocytes, CD19 + lymphocytes, and CD19 +CD38 + lymphocytes were increased significantly in patients with SLE( P