Abstract 3499: Extracellular Loop (Domain I, S5-S6) of α1D L-type Ca Channel is an Antigenic Site in Autoimmune Associated Congenital Heart Block
Bibliographic record
Abstract
Congenital heart block (CHB) is an autoimmune disease associated with autoantibodies against intracellular ribonucleoproteins SSB/La and SSA/Ro. The hallmark of CHB is complete atrioventricular block. We have established that anti-SSA/Ro -SSB/La autoantibodies inhibit L-type α 1D Ca current, I Ca-L and cross-react with the α 1D Ca channel protein. This study aims at identifying the possible binding sites on α 1D protein for autoantibodies from sera of mothers with CHB children. GST fusion proteins of the extracellular regions between the transmembrane segments (S5-S6) of each of the four α 1D Ca channel protein domains I–IV were prepared and tested for reactivity with sera from mothers with CHB children and controls using ELISA. Sera from 118 mothers with CHB children and 28 control healthy sera were used in this study. Seventeen of 118 (14.4%) maternal CHB sera reacted with the extracellular loop of Domain I S5-S6 region (E1). In contrast, 2 of 28 (7%) healthy control sera reacted with the E1 loop. Preincubation of E1 loop with the positive sera decreased the O.D. reading of the positive sera establishing the specificity of the response. Electrophysiological characterization of the ELISA positive sera demonstrated inhibition (44.1%) of the α 1D I Ca-L expressed in tsA201 cells. The inhibition was abolished when the sera were pre-incubated with E1 extracellular loop fusion protein. The results identified the extracellular loop of domain I S5-S6 of L-type Ca channel α 1D subunit as a target for autoantibodies from mothers with CHB children. This novel finding provides insights into the development of therapeutic peptides that could bind to the pathogenic antibodies.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.004 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".