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

Antibodies directed against the ribonucleoprotein complex (anti-U1RNP antibodies) are considered characteristic of mixed connective tissue disease (MCTD). Anti-U1RNP recognizes three main epitopes: 70 Kd, A (34 Kd) and C (22 Kd) proteins. Similar to other autoimmune diseases, it is currently unknown whether anti-U1RNP autoantibodies are by themselves pathogenic. The original aim of the present study was to induce in mice both a clinical syndrome resembling MCTD in humans and substantiate its pathogenic role by demonstrating the appearance in the mice sera, or murine anti-U1RNP autoantibodies. This hypothesis was formulated on the basis of previous studies conducted in other laboratories and ours, in which active immunization of BALB/c mice with different autoantibodies resulted in production of respective murine autoantibodies, and corresponding clinical manifestations. Three groups of BALB/c mice were immunized intradermally in the hind footpads with anti-U1RNP-IgG preparations obtained from three different patients withMCTD. Group 1 was immunized with human IgG#5 (U1-70Kd-A - positive), group 2 with IgG#9 (U1-70Kd - negative), U1-A, U1-C, B-B' - positive) and group 3 with IgG#4 (U1-70Kd, U1-A, U1-C - positive). Immunoblot assay showed that mice immunized with different human anti-UIRNP antibodies developed predominantly autoantibodies directed against U1 68-70 Kepitope. This pattern of antibody production has been designated by us as 'autoantibody dominance' and was not associated with respective clinical findings. This study suggests that idiotypic manipulation by active immunization of mice with different epitope specific human anti-U1RNP antibodies result in restricted production of murine epitope specific 68 -70 Kd autoantibodies.