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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.
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El complejo BAFF (factor activador de células B) compuesto por la citocina BAFF, APRIL y sus receptores -BAFF-R (BR3), TACI y BCMA- influyen en la sobrevida periférica, en la maduración de los linfocitos B y en el cambio de clase de las inmunoglobulinas, con múltiples implicaciones clínicas potenciales. Las funciones biológicas de BAFF y su relevancia en varios desórdenes clínicos -autoinmunes, neoplásicos, infecciosos, incluyendo las terapias BAFF dirigidas- son revisadas y discutidas en el presente artículo. Los niveles séricos de BAFF/APRIL se encuentran incrementados en las enfermedades autoinmunes en las que sus concentraciones se relacionan con los títulos de anticuerpos, actividad, progresión de la enfermedad e incluso compromiso orgánico, haciendo de su inhibición un blanco terapéutico atractivo
The BAFF complex (B cell activator factor) composed by the BAFF cytokine, APRIL and their receptors -BAFF-R (BR3), TACI, BCMA- influences B-lymphocyte maturation, peripheral survival and immunoglobulins class isotype switching, with multiple potential clinical implications. In this review we discuss BAFF biologic functions and it relevance in several clinical disorders -autoimmune, neoplastic, infectious and BAFF therapies-. BAFF/APRIL
Assuntos
Humanos , Doenças Autoimunes , Fator Ativador de Células BRESUMO
Objective To investigate the effects and partial mechanism of prednisone and TACI-Ig combination on MRL/Mpslac-lpr ( MRL/lpr) mice. Methods MRL/lpr mice were randomly divided into 6 groups, which includ-ed model group, prednisone (2. 5, 5. 0 mg/kg) group, TACI-Ig (15. 0 mg/kg) group, prednisone and TACI-Ig combination [(2. 5+7. 5) mg/kg, (2. 5+15. 0) mg/kg] group. BALB/c mice were set as normal group. Pred-nisone was given intragastrically everyday and TACI-Ig was given subcutaneously every two days for 13 weeks. In the meantime, the normal and model group were treated with an equal volume of normal saline. The general sign and proteinuria level were observed in the treatment period. The sections of spleen and kidney tissues for pathologi-cal analysis were stained with HE. Serum levels of auto-antibodies and BAFF were detected by ELISA kit. The per-centage of plasma cells and CD138 expression in the spleen were detected by flow cytometry analysis and immuno-histochemistry, respectively. Results The skin damage and the proteinuria level were improved and decreased by prednisone and TACI-Ig combination treatment. The spleen and kidney pathology were also improved including re-ducing germinal center formation and alleviating the glomerular fibrosis, mesangial cell hyperplasia and inflammato-ry cell infiltration, respectively. What was more, the percentage of splenic plasma cells ( CD19 -CD138 +) was re-duced significantly, which maybe resulted in the decrease in ANA. However the high level of anti-dsDNA antibody was not influenced by the combination treatment. The serum level of BAFF was also reduced by the combination treatment. Conclusion Prednisone and TACI-Ig combination treatment has a beneficial effect on murine SLE, which may be associated with the inhibition of plasma cell differentiation and the secretion of auto-antibody.
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Objective:To construct a eukaryotic vector containing human TACI-linker-BR3-IgGFc double receptor fusion gene and to investigate its expression in COS-7 cells.Methods: The standard cloning technology was employed to construct the(title) vector,which was then used to transfect COS-7 cells by lipofectamine 2000.The expression of target protein and their interaction with BAFF and APRIL protein were examined by Western blot,ELISA,and immunohistochemistry methods.Results: The expression of the fusion protein was observed in transiently transfected COS-7 cells, with the transfection efficiency being 48%.The fusion protein was detected in the supernatant.It suggested that the fusion protein interacted well with BAFF and(APRIL) proteins;the IgGFc tag did not influence the natural assembly and the biological activity of fusion proteins.Conclusion: A vector containing TACI-linker-BR3 double receptor and IgGFc fusion gene has been successfully constructed and the(subsequent) fusion protein is bioactive,which paves a way for further research on the pathogenesis of autoimmune diseases and biotherapy strategy.