Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
Yaa-Mutation Induces Phenotype Shift From Rheumatoid Arthritis to Systemic Lupus Erythematosus in FcgRIIB-Deficient B6 Mice.
Amano, Hirofumi, Kawano, Shinya, Kaneko, Toshiyuki, Sato-Hayashizaki, Aya, Qingshun, Lin, Takasaki, Yoshinari, Hirose, Sachiko
We previously obtained a FcgRIIB-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.FcgRIIB-/-.Yaa mice by introducing Yaa mutation into the RA-prone FcgRIIB-deficient B6 mice.
The Yaa mutation was introduced into FcgRIIB-/- 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.
The disease phenotype shifted from RA to SLE in B6.FcgRIIB-/-. 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.
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.
To cite this abstract, please use the following information:
Amano, Hirofumi, Kawano, Shinya, Kaneko, Toshiyuki, Sato-Hayashizaki, Aya, Qingshun, Lin, Takasaki, Yoshinari, et al; Yaa-Mutation Induces Phenotype Shift From Rheumatoid Arthritis to Systemic Lupus Erythematosus in FcgRIIB-Deficient B6 Mice. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :562