'Autoantibody dominance' pattern following idiotypic manipulation of naive mice by immunization with anti-U1RNP antibodies.

OBJECTIVE

To study the immune response and clinical findings in mice immunized with different epitope-specific anti-U1RNP antibodies purified from the sera of mixed connective tissue disease (MCTD) patients with various clinical manifestations.

METHODS

BALB/c mice were immunized with anti-U1RNP-IgG preparations from 3 patients with MCTD. Group 1 was immunized with U1 70 kD A-positive IgG, group 2 with U1 70 kD-negative, U1A, U1C, B-B'-positive IgG and group 3 with U1 70 kD, U1A, U1C-positive IgG. The induced autoantibody response in the mice was studied by ELISA and immunoblots and the clinical findings of MCTD in humans were assessed.

RESULTS

Immunoblot assays showed that mice immunized with different human anti-U1RNP antibodies developed predominantly autoantibodies directed against U1 68-70 kD epitope. This 'autoantibody dominance' pattern was not associated with clinical findings.

CONCLUSIONS

The restricted murine autoimmune response may provide clues to the diversified autoantibody production in autoimmune diseases and explain in part the changing patterns of clinical findings in individuals with MCTD.