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 systemic lupus erythematosus is frequently debated. Clinical observations indicate that anti-viral and antibacterial responses are often accompanied by self reactivity, and anti-pneumococcal antibodies elicited in non-autoimmune individuals by pneumococcal vaccine express lupus-associated anti-DNA idiotypes. To explore the relationship between protective and pathogenic antibodies in humans, we have used the phage display immunoglobulin expression system to generate a combinatorial library from spleen cells of a lupus patient immunized with a polyvalent pneumococcal polysaccharide vaccine prior to splenectomy. From this library, monovalent antigen-binding fragments expressing the 3I Vkappa1-associated idiotype were isolated. This idiotype is expressed on up to 90% of anti-DNA antibodies in the serum of lupus patients and on anti-pneumococcal antibodies in the serum of non-autoimmune individuals. Eight 3I+ monovalent antigen-binding fragments reacting with pneumococcal 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 molecular level for a potential role of molecular mimicry in the generation of anti-DNA antibodies. In addition, this is, to our knowledge, the first panel of fully sequenced human anti-pneumococcal antibodies.
Kowal
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C
Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Weinstein
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A
Diamond
B
B
D000595:Amino Acid Sequence; D000974:Antibodies, Antinuclear / Q000097:blood / Q000235:genetics; D000907:Antibodies, Bacterial / Q000097:blood / Q000235:genetics; D000916:Antibody Diversity; D000942:Antigens, Bacterial; D001324:Autoantigens; D001428:Bacterial Vaccines / Q000276:immunology / Q000494:pharmacology; D001483:Base Sequence; D003429:Cross Reactions; D004247:DNA / Q000235:genetics; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000097:blood / Q000235:genetics; D007130:Immunoglobulin Idiotypes / Q000235:genetics / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D022242:Pneumococcal Vaccines; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D013156:Splenectomy; D013296:Streptococcus pneumoniae / Q000276:immunology
D000974:Antibodies, Antinuclear; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001324:Autoantigens; D001428:Bacterial Vaccines; D007140:Immunoglobulin Fab Fragments; D007130:Immunoglobulin Idiotypes; D022242:Pneumococcal Vaccines; D004247:DNA