Abstract Session
Reproductive health
Nicola Fraser, BS
NYU Langone Health
New York, New York, United States
No financial relationships with ineligible companies to disclose
Fluids (serial dilutions 1:1,000 – 1,100,000) were evaluated for IgG and IgM titers of anti-Ro antibodies using a research ELISA. For IgG, results are considered positive at 321 ELISA units (EU) for 52kD Ro and 75 EU for 60kD Ro (mean +2 SD of values for sera from 34 healthy women during normal pregnancies). Based on evaluation of > 100 cardiac-NL mothers, a threshold risk level of 1,000 EU for either Ro specificity has been previously published.
Results:
Fluids from 3 terminated fetuses with cardiac-NL and matched maternal blood from the 2nd trimester were evaluated. All fetuses were diagnosed with advanced block in the 2nd trimester and treated with dexamethasone, IVIG, or both (Table 1). Only one pregnant patient was aware of anti-Ro and was taking hydroxychloroquine. Two fetuses showed progressive disease despite treatment prompting termination and one remained stable and terminated at parental request. Autopsy from one heart showed extensive EFE and multinucleated giant cells (fetus C). Maternal antibody reactivities to both Ro52 and 60 were in the top quartile of titers reported previously from 413 anti-Ro pregnancies. Levels of fetal IgG anti-Ro52 and 60 in the umbilical cord, pleural and pericardial space all exceeded the previously identified threshold level for risk of cardiac-NL (Table 2, Figure 1). In fetus C, levels were higher in serosal spaces than cord blood. Overall, fetal titers reached up to 15% of maternal levels for both reactivities and always matched the higher anti-Ro specificity in the pregnant patient. No IgM anti-Ro52 or 60 (FcRn does not bind IgM) were detected despite being present in the maternal circulation, confirming that the fetal anti-Ro antibodies were the consequence of placental transport and not inadvertent maternal contamination during evacuation or delivery (Table 2).
Conclusion:
Despite limited FcRn transport, maternal anti-Ro52/60 autoantibodies of IgG isotype, not IgM, are present in the 2nd trimester fetus with levels above the threshold for high risk. Analogous to the encouraging early results in antibody mediated fetal hemolytic disease, consideration of “no antibody no disease” supports the approach of FcRn as a druggable target in the prevention of cardiac-NL.
Table 1. Demographics of Pregnant Patients and Clinical Course of the Fetuses with Cardiac-NL.
NH = non-Hispanic, W = White, A = Asian, dex = dexamethasone, HCQ = hydroxychloroquine
Table 2. Levels of IgG and IgM anti-SSA/Ro 52 and 60kD Autoantibodies in the Maternal Circulation and Fetal Body Fluids at Termination. Values are shown in ELISA Units.
Figure 1. Levels of anti-Ro52 and 60 antibodies in the maternal blood, cord blood and fetal body cavities. The small dashed lines represent +2SD above the mean of healthy pregnant controls (321 ELISA units for 52kD SSA/Ro and 75 ELISA units for 60kD SSA/Ro). The dotted lines represent risk threshold levels for fetal atrioventricular block (1000 ELISA units for either specificity as previously published).
N. Fraser: None; M. Masson: None; R. Clancy: None; P. Carlucci: None; P. Izmirly: Hansoh Bio, 2; N. Sachan: None; J. Brandt: None; K. Thomas: None; M. Fox: None; C. Phoon: None; A. Ludomirsky: None; R. Srinivasan: None; G. Lam: None; B. Cuneo: None; J. Buyon: Artiva Biotherapeutics, 1, Bristol-Myers Squibb(BMS), 1, 2, Equillium, 1, GlaxoSmithKlein(GSK), 1, 2, Otsuka Pharmaceuticals, 1, Related Sciences, 1, 2.