Characterization and pathological significance of monoclonal DNA-binding antibodies from mice with experimental malaria infection.
Malaria infection is accompanied by the production of a number of autoantibodies, including some that react with DNA. Epidemiological evidence implicates these in the nephritides that arise in human quartan malaria and in experimental malaria infections in mice. Through parallels with the involvement of DNA-reactive antibodies in the autoimmune syndrome systemic lupus erythematosus, a role for DNA-reactive antibodies in forming phlogistic immune deposits in the kidneys is implied. To more fully understand the relationship between antibodies of this specificity made in malaria and systemic lupus erythematosus, we prepared monoclonal DNA-reactive antibodies from BALB/c mice infected with Plasmodium berghei (clone RC) and compared their properties with those of other antibodies previously isolated from lupous MRL/Mp lpr/lpr and (NZB x NZW)F1 mice. Antibodies from malarial mice were all immunoglobulin M class and bound to single-stranded but not double-stranded DNA in an enzyme-linked immunosorbent assay. They also reacted with synthetic polyribonucleotides in the enzyme-linked immunosorbent assay and with parasitized erythrocytes and parasite pigment in kidney sections. None of the antibodies from lupous mice had identical specificities. The potential involvement of the DNA-reactive antibodies in malarial nephritis was demonstrated, by use of immunocytochemical methods, on the basis of their binding to existing immune deposits in kidney sections from malarial mice, a similar property having been previously demonstrated for antibodies from lupous mice. Furthermore, antibodies from malarial mice expressed public idiotypes, notably Id.V-88, which is a member of the Id.16/6 family, commonly found on DNA-reactive antibodies in lupus and other infectious and connective tissue diseases. This study indicates that DNA-reactive antibodies in malaria have immunochemical properties similar but not identical to those of such antibodies in systemic lupus erythematosus and that they have the potential to participate in the formation of immune deposits in nephritic malarial kidneys.
Lloyd
C M
CM
Infection & Immunity Research Group, King's College London, United Kingdom.
Collins
I
I
Belcher
A J
AJ
Manuelpillai
N
N
Wozencraft
A O
AO
Staines
N A
NA
D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D000911:Antibodies, Monoclonal / Q000276:immunology*; D004247:DNA / Q000276:immunology*; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D007130:Immunoglobulin Idiotypes / Q000032:analysis; D007668:Kidney / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008288:Malaria / Q000276:immunology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D010962:Plasmodium berghei / Q000276:immunology*
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D007130:Immunoglobulin Idiotypes; D004247:DNA