OBJECTIVE: To determine whether La and/or Ro epitopes on apoptotic cells in fetal organs that are targeted in neonatal lupus syndrome (NLS) are accessible for binding by autoantibodies in vivo, we traced the fate of transplacental autoantibodies in a murine passive transfer model. METHODS: Pregnant mice at day 15 of gestation (E15) were injected intraperitoneally with human anti-Ro/La-positive sera or control sera, and transplacental transfer of human autoantibodies was tested by enzyme-linked immunosorbent assay with recombinant antigens. Multiple cryostat sections at the level of the heart of E17 fetuses were visualized simultaneously for human IgG binding and apoptosis (TUNEL) under confocal microscopy. Serial paraffin sections of E17 and E19 fetuses were examined for histologic evidence of inflammation. RESULTS: Human IgG anti-52-kd Ro, anti-60-kd Ro, and anti-La autoantibodies were transported efficiently into the fetal circulation. Human IgG-apoptotic cell complexes were detected in the heart (atrial trabeculae and atrioventricular node), skin, liver, and newly forming bone of fetuses from mothers injected with anti-Ro/La sera but not control sera. The IgG binding was fetal-specific and organ-specific; transplacental autoantibodies did not bind to apoptotic cells in the fetal thymus, lung, brain, or gut. The complexes were not associated with an inflammatory reaction. Injection of mothers with affinity-purified anti-La autoantibodies (but not anti-Ro/La Ig depleted of anti-La) revealed an identical location of IgG binding to apoptotic cells in the fetuses. CONCLUSION: This is the first study to demonstrate that transplacental anti-La autoantibodies bind specifically to apoptotic cells in selected fetal organs in vivo, similar to the organ involvement in NLS. We hypothesize that additional factors are required to promote proinflammatory clearance of IgG-apoptotic cell complexes and subsequent tissue damage.
OBJECTIVE: To determine whether La and/or Ro epitopes on apoptotic cells in fetal organs that are targeted in neonatal lupus syndrome (NLS) are accessible for binding by autoantibodies in vivo, we traced the fate of transplacental autoantibodies in a murine passive transfer model. METHODS: Pregnant mice at day 15 of gestation (E15) were injected intraperitoneally with human anti-Ro/La-positive sera or control sera, and transplacental transfer of human autoantibodies was tested by enzyme-linked immunosorbent assay with recombinant antigens. Multiple cryostat sections at the level of the heart of E17 fetuses were visualized simultaneously for human IgG binding and apoptosis (TUNEL) under confocal microscopy. Serial paraffin sections of E17 and E19 fetuses were examined for histologic evidence of inflammation. RESULTS:Human IgG anti-52-kd Ro, anti-60-kd Ro, and anti-La autoantibodies were transported efficiently into the fetal circulation. Human IgG-apoptotic cell complexes were detected in the heart (atrial trabeculae and atrioventricular node), skin, liver, and newly forming bone of fetuses from mothers injected with anti-Ro/La sera but not control sera. The IgG binding was fetal-specific and organ-specific; transplacental autoantibodies did not bind to apoptotic cells in the fetal thymus, lung, brain, or gut. The complexes were not associated with an inflammatory reaction. Injection of mothers with affinity-purified anti-La autoantibodies (but not anti-Ro/La Ig depleted of anti-La) revealed an identical location of IgG binding to apoptotic cells in the fetuses. CONCLUSION: This is the first study to demonstrate that transplacental anti-La autoantibodies bind specifically to apoptotic cells in selected fetal organs in vivo, similar to the organ involvement in NLS. We hypothesize that additional factors are required to promote proinflammatory clearance of IgG-apoptotic cell complexes and subsequent tissue damage.
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