title: CD20-Mimotope Peptide Active Immunotherapy in Systemic Lupus Erythematosus and a Reappraisal of Vaccination Strategies in Rheumatic Diseases.
abstract: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease in which any organs can be potential targets of autoimmune aggression. Although the pathogenic auto-antibodies have been well characterized, the role of B cells goes far beyond that of antibodies production, and B cell-targeted therapy may be an interesting therapeutic approach. The anti-CD20 monoclonal antibody rituximab has been successfully used to control the most severe form of SLE, and even if two controlled clinical trials failed to demonstrate its superiority compared to conventional immunosuppressants, off-label use of rituximab is still commonly adopted in clinical practice in SLE nephritis resistant to immunosuppressants. Different protocols have stipulated heterogeneous dosages but all of them included repeated injections of the drug, exposing the patient to the risk of adverse reactions and to tachyphylaxis (loss of the therapeutic effect). Stimulation of the host's immune system to develop a CD20 antigen-specific immune response by means of CD20-mimotope molecules may offer an approach that can overcome these drawbacks. This study provides a critical overview of vaccination therapy in rheumatic diseases and reports the design of a vaccination strategy in (New Zealand Black/New Zealand White) F1 SLE-prone mice using CD20-mimotope peptides. By week 47, this vaccine induces a B- cell depletion by 74 % (cell number, mean ± SD, 0.57 ± 0.38) as compared to week 29 (2.19 ± 0.55) (p = 0.005) and prolongs survival in peptide-treated mice (median, 46.71 weeks; 95 % CI, 39.78-53.64) as compared to the control group (median 39.85; 95 % CI, 37.41-42.30) (Kaplan-Meier p = 0.002), although no differences between the peptide group and control group were detected in terms of proteinuria and auto-antibodies titers. These data indicate the feasibility of this approach, and the mouse model described here may be useful to optimize vaccination protocol and to define the mechanism(s) underlying B- cell depletion.
authors.affiliation: Department of Biomedical Sciences and Oncology (DIMO), Systemic Rheumatic and Autoimmune Diseases, University of Bari Medical School, Piazza G. Cesare 11, 70124, Bari, Italy.
authors.forename: Elvira
authors.initials: E
authors.lastname: Favoino
authors.affiliation: Department of Biomedical Sciences and Oncology (DIMO), Systemic Rheumatic and Autoimmune Diseases, University of Bari Medical School, Piazza G. Cesare 11, 70124, Bari, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Prete
authors.affiliation: Department of Emergency and Organ Transplantation (DETO), Section of Anatomic Pathology, University of Bari Medical School, Piazza G. Cesare 11, 70124, Bari, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Marzullo
authors.affiliation: Department of Experimental Medicine-Biochemistry section and Center of Excellence for Biomedical Research University of Genoa, Viale Benedetto XV 9, 16132, Genoa, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Millo
authors.affiliation: Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Incumbent of the Laura Schwarz-Kipp Chair for Research of Autoimmune Diseases, Tel Aviv University, Tel Hashomer, 52621, Israel.
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Shoenfeld
authors.affiliation: Department of Biomedical Sciences and Oncology (DIMO), Systemic Rheumatic and Autoimmune Diseases, University of Bari Medical School, Piazza G. Cesare 11, 70124, Bari, Italy. federico.perosa@uniba.it.
authors.forename: Federico
authors.initials: F
authors.lastname: Perosa
mesh_terms: D000818:Animals; D018951:Antigens, CD20 / Q000276:immunology*; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008212:Lymphocyte Depletion / Q000379:methods*; D051379:Mice; D010455:Peptides / Q000276:immunology; D012216:Rheumatic Diseases / Q000276:immunology; D014611:Vaccination / Q000379:methods*
chemical_list: D018951:Antigens, CD20; D010455:Peptides
keywords: Autoimmune disease; CD20; Lupus-prone mice; Mimotope; Peptide; Systemic lupus erythematosus; Vaccine therapy