PT  - JOURNAL ARTICLE
AU  - S. Tengvall
AU  - T. Eneljung
AU  - I.-L. Martensson
AU  - K. Gustafsson
AU  - A. Stern
AU  - P. Jirholt
AU  - I. Gjertsson
TI  - OP0185 Endogenous B Cell-Targeted Antigen Expression Induces Tolerance to Collagen Type II Arthritis in Mice
AID  - 10.1136/annrheumdis-2013-eular.390
DP  - 2013 Jun 01
TA  - Annals of the Rheumatic Diseases
PG  - A115--A115
VI  - 72
IP  - Suppl 3
4099  - http://ard.bmj.com/content/72/Suppl_3/A115.2.short
4100  - http://ard.bmj.com/content/72/Suppl_3/A115.2.full
SO  - Ann Rheum Dis2013 Jun 01; 72
AB  - Background Rheumatoid arthritis (RA) is a destructive autoimmune disease. Today’s treatment is associated with side effects and only suppresses the disease. A safe and effective therapy would be to re-establish tolerance, i.e. the ability to recognize self. Here, we have investigated the use of gene therapy to establish tolerance in CIA, a mouse model of RA. We have previously shown that presentation of the collagen type II peptide on all types of antigen-presenting cells (APCs) can prevent development of arthritis and ameliorate ongoing disease (1). Here, we assess how targeting B cells affect tolerance induction in the CIA model. Objectives To induce tolerance in collagen induced arthritis (CIA) by endognous B cells expression of the tolerogen. Methods As gene therapy, self-inactivating lentiviral particles were used. The T cell epitope of rat collagen type II (CII) were cloned into the CLIP position of Invariant chain to allow presentation on MHC class II. As control the naturally occurring CLIP peptide was used. B cell-specific targeting was achieved by using an Ig kappa promoter. We also used B cells from mice where all types of antigen presenting cells (APCs) had been target using the spleen focus forming virus (SFFV) promoter. Haematopoetic stem cells were transduced with the lentiviral particles containing either of the constructs and transplanted into lethally irradiated DBA/1 recipient mice. After repopulation for at least 12 weeks, CIA was induced. In addition, B cells were isolated from non-immunised mice transplanted with the SFFV driven construct and transferred to naive recipients before immunisation. Results Expression of the CII epitope on all APCs abolishes the development of arthritis and decreases number of splenic plasma cells as well as the serum levels of anti-CII specific antibodies. Adoptive transfer of CD19+ B cells expressing the CII epitope derived from transplanted non-immunised mice to naïve recipients two days before CII immunisation delayed the onset and decreased the severity of arthritis compared to controls. Further, when B cells were specifically targeted using the Igk-promoter there was also a substantially decrease in arthritis development and progression. These findings were accompanied by an increased number of T regulatory cells early during the course of arthritis, and reduced serum levels of CII-specific IgG antibodies. Thus, B cells are important mediators of tolerance in CIA. Further studies are warranted to delined the exact mechanisms behind the findings, however B cell targeted therapies in RA provide interesting treatment options in a future. Conclusions Thus, B cells are important mediators of tolerance in CIA. Further studies are warranted to delined the exact mechanisms behind the findings, however B cell targeted therapies in RA provide interesting treatment options in a future. References Gjertsson I, et al. Molecular Therapy 2009 Disclosure of Interest None Declared