Session Information
Session Type: Abstract Submissions (ACR)
Background/Purpose
At birth, the human immune system expresses substantial circulating levels of polymeric IgM that include autoantibodies to oxidation-associated epitopes on apoptotic cells. This study addressed whether the neonatal IgM-repertoire may be affected by exposure to anti-Ro/La IgG-autoantibodies of maternal origin, which in some offspring leads to development of neonatal lupus.
Methods
Levels of IgM-specificities were compared in 43 healthy adults, and in umbilical cord blood (CB) from 31 unaffected newborns of non-autoimmune mothers and 103 newborns of mothers from the Research Registry for Neonatal Lupus. All mothers enrolled in the Registry have IgG anti-Ro (Ro60 and/or Ro52). In this cohort, 56 fetuses developed cardiac neonatal lupus, 4 neonates had rash, while 40 were clinically unaffected. Sandwich ELISA used phosphorylcholine (PC16)-BSA, malondialdehyde (MDA)-BSA or Ro60, with anti-IgM detection.
Results
IgM-antibodies to oxidation-associated MDA-determinants were relatively more highly represented in control newborns compared to adults (IgM anti-MDA/total IgM 7.2±3.6 CB vs 1.0±0.6 adults) while the ratio IgM anti-PC/total IgM was lower (2.7±1.7 vs 10.7±5.6, p<0.0001). CB levels of IgM anti-MDA directly correlated with IgM binding to apoptotic cells. In neonates exposed to IgG anti-Ro, total IgM and IgM anti-Ro60 were significantly elevated compared to control neonates (41±39 RU/ml vs 27±18, p=0.008; 218±203 RU/ml vs 129±115 RU/ml, p=0.003, respectively). Similarly, the ratio of IgM anti-Ro60 was higher in these newborns compared to controls (8.6±9.6 vs 5.0±2.8, p=0.001). No correlation between IgM and IgG anti-Ro60 or RF IgM in CB could be detected. In contrast, the proportion of IgM anti-MDA was significantly lower in CB from neonates exposed to IgG anti-Ro60 mothers compared to controls (4.8±4.7 vs 7.2±3.6, p=0.004). Neither the development of heart block, nor the disease status of the mothers, was associated with differences in neonatal IgM levels.
Conclusion
These findings document the relative dominance in the neonate of specificities of IgM-autoantibodies to oxidation-associated neo-determinants associated with protective properties in other settings. These data suggest that early immune development of the natural IgM-repertoire may become imprinted by maternally transferred anti-Ro60 IgG-autoantibodies.
Disclosure:
C. Grönwall,
None;
R. M. Clancy,
None;
L. Getu,
None;
D. L. Siegel,
None;
J. Reed,
None;
J. P. Buyon,
None;
G. J. Silverman,
None.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/modulation-of-natural-igm-autoantibodies-to-oxidative-stress-related-neo-epitopes-on-apoptotic-cells-in-newborns-of-mothers-with-anti-ro-autoimmunity/