CD20-Mimotope Peptide Active Immunotherapy in Systemic Lupus Erythematosus and a Reappraisal of Vaccination Strategies in Rheumatic Diseases

摘要: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which any organs can be potential targets of aggression. Although the pathogenic auto-antibodies have been well characterized, role B cells goes far beyond that antibodies production, and cell-targeted therapy may an interesting therapeutic approach. The anti-CD20 monoclonal antibody rituximab has successfully used to control most severe form SLE, even if two controlled clinical trials failed demonstrate its superiority compared conventional immunosuppressants, off-label use still commonly adopted practice SLE nephritis resistant immunosuppressants. Different protocols stipulated heterogeneous dosages but all them included repeated injections drug, exposing patient risk adverse reactions tachyphylaxis (loss effect). Stimulation host's immune system develop CD20 antigen-specific response by means CD20-mimotope molecules offer approach overcome these drawbacks. This study provides critical overview vaccination rheumatic diseases reports design strategy (New Zealand Black/New White) F1 SLE-prone mice using peptides. By week 47, this vaccine induces B- cell depletion 74 % (cell number, mean ± SD, 0.57 ± 0.38) as 29 (2.19 ± 0.55) (p = 0.005) prolongs survival peptide-treated (median, 46.71 weeks; 95 % CI, 39.78-53.64) group (median 39.85; 37.41-42.30) (Kaplan-Meier p = 0.002), although no differences between peptide were detected terms proteinuria titers. These data indicate feasibility approach, mouse model described here useful optimize protocol define mechanism(s) underlying depletion.