Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Immunization with Ro60 Peptide Leads to Sjgren's Like Syndrome in Mice with Appropriate Genetic Background.
Kurien1, Biji T., Asfa3, Sima, D'souza3, Anil, Dorri3, Yaser, Dillon3, Skyler P., Hubbel3, Sherry, Khalili2, Ali W.
Our previous studies showed that BALB/c mice are amenable as an animal model for Sjögren's syndrome (SS) with (a) diminished salivary flow (b) intramolecular epitope spreading to Ro 60 autoantigen and (c) salivary gland lymphocytic infiltration upon immunization with Ro 274 peptide derived from Ro 60 autoantigen. We hypothesized that there would be a strain dependent susceptibility for SS induction.
Fourteen mice each from BALB/c, DBA-2, SJL/J, C57Bl/6 and PL/J strains were used. Seven mice from each strain were immunized (day one) with 50 mg of a linear peptide (273289 amino acid sequence from Ro 60) or saline emulsified in Freund's Complete Adjuvant (FCA). Subsequent boosts were in Freund's Incomplete Adjuvant. The first, second and third boosts were given on day 7, 27 and 60 respectively. Ro 60 multiple antigenic peptide ELISA, Ro 60 ELISA and immunoblots were performed. Epitope spreading, salivary flow (upon induction with pilocarpine and isoproterenol) and histochemical lymphocytic infiltration were determined. Upon sacrifice, salivary glands were excised and a portion was saved for histopathological studies.
Immunization with Ro-274 linear peptide resulted in anti-Ro-274 antibodies as early as the first bleed in BALB/c, DBA-2 and PL/J strain of mice. A milder anti-Ro 274 response was elicited in the B6 strain of mice by the sixth bleed while the SJL/J mice displayed a very poor response throughout the study. In the Ro-274 peptide immunized group 5/5 BALB/c, 1/5 DBA, 3/4 PL/J mice bound Ro 60 antigen by immunoblot. SJL/J and C57Bl/6 mice did not bind. Except for one DBA control mice that bound Ro 60 antigen on immunoblot the remaining control mice did not make antibodies to this antigen. Ro-peptide immunized BALB/c and DBA mice had lymphocytic infiltration of the salivary glands greater than controls However, salivary flow was significantly decreased only in the BALB/c mice compared to controls.
Only BALB/c mice displayed the complete SS-like condition, with diminished salivary flow, anti-Ro 60 antibodies and salivary gland lymphocytic infiltration upon immunization with Ro 274 peptide. DBA mice had significant salivary infiltrates and anti-Ro 60 antibodies but no salivary dysfunction. PL/J mice made antibodies and had epitope spreading but did not have salivary pathology or dysfunction. C57Bl6 bound the peptide but had no further progression in the model while SJL/J never produced antibodies to the immunogen, These data suggest a stepwise, or quantum, genetic control of the response that leads to a Sjögren's-like illness after Ro-peptide immunization.
To cite this abstract, please use the following information:
Kurien, Biji T., Asfa, Sima, D'souza, Anil, Dorri, Yaser, Dillon, Skyler P., Hubbel, Sherry, et al; Immunization with Ro60 Peptide Leads to Sjgren's Like Syndrome in Mice with Appropriate Genetic Background. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :1901