Molecular mimicry between bacterial and self antigen in a patient with systemic lupus erythematosus

The importance of microbial infection as a trigger for the induction of sys temic lupus erythematosus is frequently debated. Clinical observations indi cate that anti-viral and antibacterial responses are often accompanied by s elf reactivity, and anti-pneumococcal antibodies elicited in non-autoimmune individuals by pneumococcal vaccine express lupus-associated anti-DNA idio types. To explore the relationship between protective and pathogenic antibo dies in humans, we have used the phage display immunoglobulin expression sy stem to generate a combinatorial library from spleen cells of a lupus patie nt immunized with a polyvalent pneumococcal polysaccharide vaccine prior to splenectomy. From this library, monovalent antigen-binding fragments expre ssing the 31 V kappa 1-associated idiotype were isolated. This idiotype is expressed on up to 90 % of anti-DNA antibodies in the serum of lupus patien ts and on anti-pneumococcal antibodies in the serum of non-autoimmune indiv iduals. Eight 31(+) monovalent antigen-binding fragments reacting with pneu mococcal polysaccharide, DNA or both were analyzed. Four of these fragments were cross-reactive with both foreign and self antigen, demonstrating that a high percentage of anti-bacterial antibodies produced in a patient with lupus bind double-stranded DNA. These studies provide support at the molecu lar level for a potential role of molecular mimicry in the generation of an ti-DNA antibodies. In addition, this is, to our knowledge, the first panel of fully sequenced human anti-pneumococcal antibodies.