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Preliminary Study Of Sm Antigen Mimic Epitope Peptide-induced Immune Tolerance Therapies Against Systemic Lupus Erythematosus Like Mice

Posted on:2008-10-10Degree:MasterType:Thesis
Country:ChinaCandidate:H Y CengFull Text:PDF
GTID:2144360215985984Subject:Dermatology and Venereology
Abstract/Summary:PDF Full Text Request
ObjectiveTo explore the possibility of inducing immune tolerance of SLEsyndrome mice which were immunized with the single Sm mimic epitopepeptide.Methods20 positive clones (single epitope peptides) were selected randomlyfrom the third elute and identified by ELISA and DNA sequencing. Inimmune tolerance research, 40 SLE syndrome model BALB/c mice wererandomly divided into 5 equal groups: Sm-3# group, Sm-6# group, Sm-9#group, Sm-11# group and model control group; The SLE syndrome micewere vena caudalis with epitope peptide Sm-3#, Sm-6#, Sm-9# Sm-11#(0.8×1018pfu/per mouse) in saline, respectively, and repeatedly inject sixtimes(0-14-28-42-49-56d); The model control group received onlyoriginal Phage Display Peptide Library. The animals were sacrificed 70days later. The autoantibody(ANA and dsDNA) of each group was thendetermined; Kidneys tissues were taken for histological HE staining and detection of autoantibodies with immunofluorescent staining, besides, theurine protein of each group were also detected.Results1. Four epitope peptides phage clones were found strongly positiveby evaluating the binding to Sm antibody by ELISA, the amino acidsequences were deduced from the four phage clones by sequencing.2. Remarkably, tolerization with the Sm antigen mimic epitope-Sm11# injected into SLE syndrome model mice inhibiting the productionof multiple pathogenic autoantibodies, was significantly lower than inmice of the model control group(P<0.05); The level of urine protein inmice of Sm11# treated group was significantly lower than the controlgroup and other treated groups(P<0.05). Moreover, repeated injection ofSm11# even halted the progression of renal disease through histologicalHE staining and immunofluorescent staining assays. However, thestrikingly therapy effect were not fotmd by the other 3 Sm mimicepitopes.ConclusionsTolerance therapy with select Sm mimic epitope peptides works bysuppress the production of pathogenic autoantibodies and especially inhibit inflammatory insults in the lupus kidney. So it may lead todevelop a novel way to treat SLE based on Sm mimic epitope-basedimmune tolerance study.
Keywords/Search Tags:Systemic lupus erythematosus, Smith antigen, Phage displayed peptide library, mimic epitope, immune tolerance
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