Lupus & antiphospholipid syndrome
Maternal autoantibodies to the sodium potassium pump α1 subunit AT1A1 and fetal autoimmune congenital heart block: a case-control study
An erratum to this article was published (Lancet Rheumatol, Nov 2025 ↗)
Authors' conclusion
This study identifies a novel maternal autoantibody targeting the fetal AT1A1 cardiac protein as a potential biomarker for the early and accurate detection of fetal autoimmune congenital heart block in pregnant women who had not previously had an affected pregnancy.
Study context
- Population
- Anti-SSA/Ro-positive pregnancies at risk due to maternal SLE, SjD, UCTD or a history of congenital heart block offspring; The Hospital for Sick Children, Canada, and University of Padua, Italy
- Participants
- 46 vs 65
- Comparison
- Pregnancies affected by fetal autoimmune congenital heart block vs unaffected pregnancies
- Casesn = 46
- Controlsn = 65reference
- Outcome
- Presence and specificity of anti-cardiac autoantibodies in cases vs controls, association of specific autoantibodies with congenital heart block, and predictive accuracy of identified autoantibodies
Methodological detailstwo centres, discovery, verification and validation cohorts
- Two centres
- Discovery, verification and validation cohorts
Main finding
As reported in the abstract
Maternal anti-AT1A1 autoantibodies
| Group | Value | Discovery cohort | Verification cohort | Validation cohort |
|---|---|---|---|---|
| Cases | 100% | six [100%] of six | 22 [100%] of 22 | 16 [100%] of 16 |
Cases
Value100%
Discovery cohortsix [100%] of six
Verification cohort22 [100%] of 22
Validation cohort16 [100%] of 16
- Anti-AT1A1 absent in all unaffected pregnancies in pregnant women with no fetal heart block history
- 54/65 [83%]
Observational data: associations, not effects.
Further findings
Potential cardiac protein targets of maternal autoantibodies
- Potential targets identified by mass spectrometry
- 11
- Autoantibodies confirmed in serum from affected pregnancies
- seven
- Targets identified before onset of congenital heart block (ANXA1, BIP, MYPC3, AT1A1)
- Four
Original publication
Maternal autoantibodies to the sodium potassium pump α1 subunit AT1A1 and fetal autoimmune congenital heart block: a case-control study. Lancet Rheumatol. Published 21 May 2025. doi:10.
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