Idiotypic cross-reactions of monoclonal human lupus autoantibodies.

TLDR

The study examined idiotypic cross‑reactions among 60 monoclonal lupus autoantibodies from seven patients and generated three anti‑idiotype reagents by immunizing rabbits and a mouse with monoclonal antibodies from two patients. Binding of the anti‑idiotype reagents was inhibited by polynucleotides, indicating they target variable regions; 40 of 60 monoclonal autoantibodies reacted in competitive assays (15 with all three reagents), suggesting that lupus autoantibodies from unrelated patients arise from related germ‑line gene families.

Abstract

Idiotypic cross-reactions were evaluated in 60 polynucleotide-binding monoclonal lupus autoantibodies produced by human-human hybridomas that were derived from seven unrelated patients with SLE. Three antiidiotype reagents were prepared by immunization of rabbits or a mouse with monoclonal autoantibodies from two patients. Binding of the three reagents to their corresponding idiotypes was inhibited by one or more polynucleotides, an indication that the antiidiotypes reacted with the variable regions of the autoantibodies. Each antiidiotype appeared to detect a different idiotypic determinant. Of the 60 monoclonal autoantibodies tested, 40 reacted in one or more competitive immunoassays; 15 reacted with one antiidiotype, 10 reacted with two antiidiotypes and 15 reacted with three antiidiotypes. A monoclonal antiidiotype reagent cross-reacted with autoantibodies from six of the seven patients. The idiotypic cross-reactions of immunoglobulins from unrelated patients suggest that the autoantibodies are derived from related families of germ line genes that are expressed by patients with SLE.