562 - Yaa-Mutation Induces Phenotype Shift From Rheumatoid Arthritis to Systemic Lupus Erythematosus in FcgRIIB-Deficient B6 Mice

Sunday, November 6, 2011: 9:00 AM-6:00 PM
Hall F2 - Poster Hall (McCormick Place West)
Hirofumi Amano, Shinya Kawano, Toshiyuki Kaneko, Aya Sato-Hayashizaki, Lin Qingshun, Yoshinari Takasaki and Sachiko Hirose, Juntendo University School of Medicine, Tokyo, Japan
Presentation Number: 562

Background/Purpose:  We previously obtained a FcγRIIB-deficient C57BL/6 (B6) congenic strain of mice, which spontaneously developed severe rheumatoid arthritis (RA). The development of systemic lupus is accelerated by the Yaa (Y-linked autoimmune acceleration) mutation, which is a consequence of a translocation from the telomeric end of the X chromosome containing the Tlr7 gene onto the Y chromosome. To examine the effect of the Yaa mutation on the autoimmune disease phenotype in this strain, we established B6.FcγRIIB-/-.Yaa mice by introducing Yaa mutation into the RA-prone FcγRIIB-deficient B6 mice. Method:The Yaa mutation was introduced into FcγRIIB-/- mice from B6.Yaa mice. Serum levels of RF, IgG antibodies against double-stranded DNA and chromatin were measured using ELISA. The severity of renal disease was monitored by biweekly testing for proteinuria.Histopathological examination was also performed. Result:The disease phenotype shifted from RA to SLE in B6.FcγRIIB-/-.Yaa mice.They did not develop RA, instead they showed the marked increase in serum levels of rheumatoid factor and SLE-related autoantibodies such as anti-chromatin and anti-ds DNA antibodies. These developed glomerulonephritis with the high incidence of positive proteinuria even at 6 months of age.Conclusion:The present studies suggest that the common genetic pathways play a role in the disease process shared by RA and SLE, and the environmental factors such as the stimulation of innate immune system may control separate autoimmune diseases RA and SLE.

Keywords: Fc receptors, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE)

Disclosure: H. Amano, None; S. Kawano, None; T. Kaneko, None; A. Sato-Hayashizaki, None; L. Qingshun, None; Y. Takasaki, None; S. Hirose, None.