Role of DNA-binding antibodies in kidney pathology associated with murine malaria infections.
We performed a series of studies to examine the sequential development of nephritis during murine malaria infections and to define the role of DNA-binding antibodies in the associated pathology. Serum levels of these antibodies were assessed throughout acute and chronic malaria infections. Increased levels of double-stranded DNA- and single-stranded DNA-binding antibodies were initially detected in mice infected with Plasmodium vinckei or Plasmodium yoelii nigeriensis during the middle stages of infection, and these levels were maintained until death. Infection with the more chronic organism Plasmodium berghei clone RC also resulted in increased single-stranded DNA-binding antibody titers, which fluctuated as the infection progressed. All three species caused kidney damage and dysfunction, as assessed by changes in morphology, blood urea nitrogen, and excreted albumin; this damage correlated with the extent of parasitemia and was observed before the levels of DNA-binding antibodies were detectably elevated in the serum. However, the results of immunohistochemical studies demonstrated that DNA-binding monoclonal antibodies bound ex vivo to glomeruli within kidneys prepared from mice at late stages of infection, after the initial damage had been incurred. Our findings suggest how DNA-binding antibodies could contribute to the kidney pathology associated with both malaria and certain autoimmune diseases, such as systemic lupus erythematosus.
Wozencraft
A O
AO
Division of Biomolecular Sciences, King's College, London, United Kingdom.
Lloyd
C M
CM
Staines
N A
NA
Griffiths
V J
VJ
D000208:Acute Disease; D000818:Animals; D000974:Antibodies, Antinuclear / Q000276:immunology*; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex / Q000032:analysis; D001323:Autoantibodies / Q000032:analysis; D002908:Chronic Disease; D004247:DNA / Q000276:immunology; D005260:Female; D007668:Kidney / Q000473:pathology; D007677:Kidney Function Tests; D008288:Malaria / Q000150:complications* / Q000276:immunology; D051379:Mice; D009393:Nephritis / Q000209:etiology* / Q000276:immunology; D013997:Time Factors
D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D004247:DNA